Calibrated measurement of blood vessels and endothelium after reactive hyperemia and method therefor

The calibrated method for characterizing blood flow in a limb of a patient during reactive hyperemia utilizes a blood pressure cuff. The method establishes a predetermined, near diastolic, pressure in said blood pressure cuff during the reactive hyperemic episode, continually senses the pressure in the cuff and periodically changes the internal volume of said blood pressure cuff by a predetermined volumetric amount to calibrate the system. The resultant change in the pressure is a calibration pressure pulse and is used to calculates pulsatile blood volume through the blood vessel. A calibrated method for determining the condition of blood vessels and endothelium includes determining, for each calibration cycle, a respective peak value for the blood volume and comparing the peak blood volume values with peak blood volume values for healthy blood vessels and endothelium. The comparison preferably utilizes a waveform. The calibrated system for characterizing blood flow includes a computerized electronic and pneumatic system which inflates, for a predetermined pre-test time, the blood pressure cuff to a suprasystolic pressure and thereafter establishes the near diastolic pressure in the cuff during the ensuing reactive hyperemic episode. A sensor substantially continually senses the pressure and generates a pressure signal. A subsystem periodically changes the volume of said blood pressure cuff during a calibration cycle. A corrected and calibrated blood volume signal is calculated with the calibration pressure signal. A calibrated system for determining the condition of blood vessels and endothelium is also disclosed.

The present invention relates to the calibrated measurement of blood 
vessels, particularly arterial blood vessels, and the physiologic change 
of the endothelium, resulting from the generation of nitric oxide (NO), 
after reactive hyperemia and a method therefor. 
BACKGROUND OF THE INVENTION 
Researchers have observed that endothelial dysfunction is an early event in 
the pathogenesis of cardiovascular disease. The role of endothelium in 
maintaining cardiovascular health is fairly well documented. Endothelial 
dysfunction and coronary artery disease (CAD) are also linked to 
hypertension, hypercholesterolemia diabetes mellitus and cigarette 
smoking. Dietary and lifestyle modification, in addition to anti-oxidant 
vitamin supplementation, have been demonstrated to have a beneficial 
affect on endothelial function. Clinical Implications of Endothelial 
Dysfunction, C. Pepine, Clinical Cardiology, Vol. 21, November, 1998, pp. 
795-799. Other researchers have observed that the vascular endothelium, 
the cells lining the interior portion of arteries, plays a fundamental 
role in several processes related to hemostasis thrombosis. These 
researchers have proposed that endothelial function may provide guidance 
to developing new strategies for coronary disease prevention and 
treatment. Nontraditional Coronary Risk Factors and Vascular Biology: The 
Frontiers of Preventive Cardiology, by P. Ridker et al., J. of 
Investigative Medicine, Vol. 46, No. 8, October, 1998, pp. 348-350. At 
present, the full range of different diseases associated with endothelial 
dysfunction remains to be determined, the nature of the abnormalities 
defined and measured, and the effects of potential treatments evaluated. 
To some degree, the health and the condition of the endothelium is also 
related to the ability of that cellular layer to generate and transmit 
nitric oxide (NO) as a biomarker throughout the tissues of the arterial 
wall. Most recently, Nobel Prize winners Robert F. Furchgott, Ferid Murad 
and Louis J. Ignarro have linked the production and transmission of NO 
through the endothelium as being the primary indicator associated with 
vascular dilation. Previously, researchers theorized that vascular 
dilation was triggered by an agent named "endothelium-derived relaxing 
factor" or EDRF. With the association established by Furchgott, Murad and 
Ignarro, researchers now believe that NO is the dominant, if not exclusive 
EDRF and is directly related to the health and condition of the 
endothelium and the ability of the endothelium to dilate the arteries of a 
person. The Nature of Endothelium-Derived Relaxation Factor, R. Furchgott, 
Nov. 16, 1998, at the "www" website hscbklyn.edu/pharmacology/furch.htm; 
Research Interests: nitric oxide; cyclic gmp, cell signaling, second 
messengers, regulatory biology, molecular pharmacology, F. Murad, Nov. 15, 
1998, at the "http" website girch 
z.med.uth.tmc.edu/faculty/fmurad/index.cfm; and, Nitric Oxide and Cyclic 
GMP Signal Transduction Mechanisms, L. Ignarro, Nov. 15, 1998, at the 
"www" website nuc.ucla.edu/html-docs/faculty-docs/ignarro.html. 
Accordingly, current research now indicates that NO is generated by the 
endothelium and is transmitted through the endothelium and that NO is a 
biomarker for vascular dilation. 
Medical professionals have, in the past, sought to determine the health of 
a patient's vascular system by monitoring the physiological conditions or 
characteristics of the arteries in a patient's limb after reactive 
hyperemia. Reactive hyperemia occurs in a patient after a major artery has 
been blocked off or closed by a blood pressure cuff inflated slightly 
above systolic pressure for approximately five minutes. The limb, 
downstream from the blocked artery, suffers anoxia or severe hypoxia. Upon 
a sudden release of the blood pressure cuff, the endothelial cells lining 
the interior of the arterial wall react by generating NO and by dilating. 
This vascular dilation and expansion results in the expansion of resistive 
arterial vessels and associated muscles significantly downstream from site 
of the previously collapsed artery. The resistive arterial vessels enlarge 
based upon the NO biomarker, transmit NO through other parts of the 
endothelium and may cause reactive hyperemia in the limb. Reactive 
hyperemia is a significantly greater flow of blood through an artery, vein 
or limb as compared with normal blood flow therethrough. Blood flow is a 
characteristic of the artery and is typically a quantitative measurement 
of blood volume with respect to time (e.g. ml per minute). Generally, the 
phenomenon of reactive hyperemia lasts up to 10 minutes before return to 
pre-test pulse volume values. 
Some medical professionals utilize pulse volume recorders to measure the 
peak pressure (mmHg) in the arteries immediately after the release of the 
blood pressure cuff and ischemia. However, these researches measure only 
the peak pressure during the reactive hyperemia and typically do not 
continuously measure blood volume or blood flow or the pulsatile blood 
volume change through the arteries in the limb during the entire reactive 
hyperemia episode, i.e., until return to the pre-episode state. The 
methods of pulse volume measurements have not been standardized by a 
national consensus panel of investigators. 
Other researchers studying the effect of reactive hyperemia on a vascular 
system utilize ultrasound imaging techniques to capture an image of the 
brachial artery (the artery which is blocked to achieve reactive hyperemia 
in the arm of the patient) and measure the changing diameter of the 
brachial artery. Technicians measure the diameter of the artery before the 
ischemia (prior to reactive hyperemia and closure of the vascular system) 
by capturing electronic ultrasonic images. Subsequently, technicians 
attempt to detect and measure the largest expansion of the diameter of the 
brachial artery after ischemia and during the reactive hyperemia episode. 
These medical professionals then compute (with simple geometric equations) 
the expansion of the artery and the volume change of the artery. However, 
the use of an ultrasound image to measure the expansion of the brachial 
artery during reactive hyperemia has many technical problems that may 
jeopardize the measurement's accuracy and precision. 
Researchers have observed that the brachial artery diameter typically 
expands about 0.3 mm during reactive hyperemia. Reproducibility of 
Brachial Ultrasonography and Flow-Mediated Dilation (FMD) for Assessing 
Endothelial Function, by K. L. Hardie, et al., Australian New Zealand 
Journal of Medicine, 27, pp.649-652, 1997 (this study revealed arterial 
diameter of 3.78 mm at rest; 3.89 mm during reactive hyperemia). Other 
studies show diameters of 3.92 mm at rest increasing to 4.13 mm during 
reactive hyperemia. Noninvasive Assessment of Endothelium-Dependent 
Flow-Mediated Dilation of the Brachial Artery, by A. Uehata et al, 
Vascular Medicine 2, pp. 87-92, 1997. Studies have shown that the effect 
of nitroglycerin treatment during reactive hyperemia increases the 
expansion of the arterial diameter by about 11%. Flow-Induced Vasodilation 
of the Human Brachial Artery is Impaired in Patient [over] 40 years of Age 
with Coronary Artery Disease, by E. Lieberman, et al., American Journal of 
Cardiology, 78, pp. 1210-1214, 1996. Nitroglycerin is converted into NO 
and this additional NO stimulates vascular dilation. This study has 
indicated that young people, without any indication of coronary artery 
disease (healthy individuals), exhibit an increase in the diameter of the 
brachial arterial on the order of 6.2%. In contrast, young people with 
coronary artery disease exhibit an arterial diameter increase of only 
1.3%. This same study measured arterial diameters utilizing ultrasonic 
techniques and revealed measurement errors of plus or minus 1.1% for the 
diseased population typical (arterial expansion of 1.3%). Errors of 0.7% 
were noted during the ultrasonic measurement of the brachial arteries in 
the healthy population (typical arterial change of 6.2%). Accordingly, 
these studies show a coefficient of error or variation of almost 30% with 
utilization of ultrasonic techniques. These errors are caused by the 
acquisition of the electronic image data capturing the expansion of the 
brachial artery during reactive hyperemia, the measurement of the 
electronic image and the introduction of arithmetic errors into the 
calculation of the arterial diameter. 
Currently, many researchers utilize ultrasonic techniques to noninvasively 
detect the increase of the diameter of the artery during reactive 
hyperemia. The use of ultrasonic imaging techniques has many problems. For 
example, the ultrasound technician operator must carefully place the 
ultrasound scanning head on and above the brachial artery at a certain x-y 
and z position relative to the patient's skin. The ultrasound head is 
typically placed a few inches above the crease in the patient's elbow. If 
the operator places the ultrasound head at a different location on another 
patient or if the operator places the ultrasound head at a different 
location on the same patient at a different clinical testing time, the 
data obtained during these inter-patient and intra-patient tests is not 
consistent. Further, the ultrasound operator must place the ultrasound 
head on the patient, move the ultrasound head longitudinally up and down 
the patient's arm, move the head laterally side to side about the arm and 
rotate the angle of the ultrasound head relative to the surface of the 
skin in order to obtain a clear electronic image of the brachial artery. 
This involves multiple eye-hand coordination by the operator since the 
operator views the image while he or she moves the ultrasound head over 
the patient's arm. Further, after the operator correctly positions and 
obtains a clear electronic image, the operator must then issue (a) a cuff 
release command to begin the reactive hyperemia and (b) a record command 
to the ultrasound equipment which begins recording the image. The 
ultrasound operator may also be required to move electronic calipers on 
the captured electronic image at the same time as he or she is capturing 
additional images in order to measure the expanded diameter of the 
brachial artery during reactive hyperemia. Specifically, the ultrasound 
operator quickly releases the blood pressure cuff which occluded the 
brachial artery for about five (5) minutes and initiates reactive 
hyperemia in the limb. During the first minute after cuff release, the 
ultrasound operator carefully positions the ultrasound head on the skin of 
the patient. During the next thirty seconds, the operator captures the 
ultrasound image of the expanded diameter of the brachial artery as a 
recorded electronic image and measures the increase of the arterial 
diameter. This measurement normally includes the use of electronic 
calipers on the display screen. In the third sixty second period, the 
operator continues to electronically monitor and store the image of the 
brachial artery as the arterial diameter reduces in size during the latter 
portions of the reactive hyperemia episode. 
After the ultrasound operator captures this electronic image, the operator 
or other health professional can view or re-play the stored electronic 
image and seek to identify the largest expansion of the diameter of the 
brachial artery. Accordingly, it is difficult to obtain this data with 
ultrasound equipment, to replicate the test on the same patient, to 
replicate the same test on a different patient, to interpret the 
electronic image and to quantify the amount of arterial expansion. 
These problems with respect to ultrasound imagery and the interpretation of 
the captured image have inhibited researchers from reproducing earlier 
experiments and confirming experiments conducted by other researchers and 
combining or correlating data from various studies. The current lack of 
standardization of methods prevents definitive studies among 
investigators. 
Further, since ultrasonic imagery measures only an increase in the diameter 
of an artery, any error introduced by this measurement is amplified since 
it is squared in the mathematic formulas for the area A of a circle and 
the volume V of a tubular structure such as an artery. The equation for 
area A follows: 
EQU A=(1/4).pi.d.sup.2 Eq. 1 
The equation for the volume V of a cylinder follows. 
EQU V=(1/4).pi.d.sup.2 1 Eq. 2 
The length of the ultrasound head is utilized to estimate the length 1 of 
the generally cylindrical arterial vessel. This formula establishes the 
volume of the arterial segment and the change in volume of the arterial 
segment during reactive hyperemia. Accordingly, any error introduced into 
the measurement of the diameter d of the artery is squared by the 
volumetric formula Eq. 2 and the system operator can only estimate the 
length 1 of arterial segment based upon the size of the ultrasound head. 
This estimate of length 1 also introduces another element of error into 
the measurement of the volumetric change of the blood vessel during 
reactive hyperemia. 
U.S. Pat. No. 5,718,232 to Raines, et al. and U.S. Pat. No. 5,630,424 to 
Raines, et al. describe a calibration system for measuring segmental blood 
volume changes in arteries and veins for pulse volume recorders. The pulse 
volume recorders described in Raines '232 and Raines '424 add or subtract 
a predetermined volume (approximately 1 ml) to or from the volume of the 
pneumatic blood pressure cuff system at each cuff pressure over a 
plurality or multiple levels of induced cuff pressure. Basically, Raines 
'232 and Raines '424 seek a solution to the problem that the pneumatic 
response of the blood pressure cuff system due to blood pressure pulse 
waves changes at each discrete level of induced cuff pressure (the 
response delta P changes at each cuff lever Pcuff 40, 50, 60, 70, 80, and 
90 mmHg.). In order to measure and calibrate the blood pressure system at 
each discrete cuff level, the predetermined volumetric amount is added or 
withdrawn from the pneumatic system at that induced cuff pressure level. 
By measuring the pressure change at the time of the volumetric calibration 
pulse, the resulting pressure wave signal is a calibration pressure pulse. 
The sensed pressure wave signal at the induced cuff pressure is converted 
into a corrected blood volume signal using the ratio of the volumetric 
calibration pulse versus the calibration pressure pulse. This is a direct 
measurement of blood volume and a basis for blood flow at the induced 
pressure level. 
Specifically, the Raines '232 and the Raines '424 patents utilize a blood 
pressure cuff placed around the limb of a patient. The blood pressure cuff 
was pumped up or inflated to certain predetermined cuff levels such as 40, 
50, 60, 70 mmHg through 120 mmHg. At each discrete cuff pressure level 
Pcuff, the system was calibrated in order to obtain a corrected blood 
volume signal change at each cuff pressure level. After the corrected 
blood volume data was obtained, a ratio was generated between blood volume 
change in relation to the pressure change at the selected induced cuff 
pressure in order to determine the maximum value of the blood volume 
versus the sensed pressure differential. The maximal ratio of blood volume 
change versus blood pressure change at a particular cuff pressure provides 
an indication of the onset and the degree of atherosclerosis in humans as 
well as provides an indication of the health or condition of the vascular 
system and particularly of the peripheral vascular system. The contents 
and substance of U.S. Pat. No. 5,718,232 to Raines et al. and U.S. Pat. 
No. 5,630,424 to Raines et al. is incorporated herein by reference 
thereto. The relationship between atherosclerosis and the maximal ratio of 
delta V over delta P (peak arterial compliance) is disclosed in U.S. Pat. 
No. 5,241,963 to Shankar. The content of U.S. Pat. No. 5,241,963 is 
incorporated herein by reference thereto. 
OBJECTS OF THE INVENTION 
It is an object of the present invention to provide acalibrated measurement 
system to measure the dilation of blood vessels in a patient's limb and to 
measure the endothelium after reactive hyperemia. 
It is an additional object of the present invention to provide a calibrated 
measurement system to measure the dilation of arterial blood vessels and 
to indirectly measure the endothelium's production of NO and the arterial 
dilation response to the NO after reactive hyperemia. Also, it is an 
object of the present invention to measure those items before and after 
the administration of other agents producing similar alterations of 
arterial reactions. 
It is another object of the present invention to provide a method for 
obtaining a calibrated measurement of blood vessels and endothelium after 
reactive hyperemia. 
It is an object of the present invention to provide a clinical diagnostic 
and evaluation method for obtaining a calibrated measurement of the change 
of volume of arterial blood vessels and endothelium after production of 
reactive hyperemia. 
It is a further object of the present invention to provide an internal 
calibration system for measuring the dilation of blood vessels and the 
effects on the endothelium during the entire reactive hyperemia episode. 
It is additional object of the present invention to capture pressure pulse 
data (which may be waveform and/or tabular data), periodically calibrate 
the pneumatic system, and calculate the blood volume data and waveform, if 
necessary, and the blood flow (q versus t) during the entire reactive 
hyperemia episode. The data capture and processing is preferably, 
essentially continuous, however, the processing may be conducted during a 
post-examination time or off-line rather than in real time, during the 
reactive hyperemia (RHT) test. 
It is another object of the present invention to provide multiple and 
periodic calibrations of the pneumatic system during the entire reactive 
hyperemia episode. 
It is an additional object of the present invention to provide a pneumatic 
system which automatically initiates the quick pressure release of the 
blood pressure cuff pneumatic system, quickly achieves a predetermined 
diastolic or near diastolic cuff pressure in the blood pressure cuff 
pneumatic system and monitors and calibrates pressure pulse waves during 
substantially all of the reactive hyperemia episode. 
It is an additional object of the present invention to measure the effects 
of reactive hyperemia on all the blood vessels (primarily arterial blood 
vessels) and endothelium of the patient rather than simply the brachial 
artery of the patient. Further, the RHT test may be conducted on the major 
distal portion of each of the four limbs of the patent. This technique 
potentially enhances the quality of test's overall results. 
It is a further object of the present invention to plot, map and/or record 
calibrated blood volume data and/or the blood flow data during 
substantially all of the reactive hyperemia episode in order to correlate 
the health and condition of the endothelium and the coronary artery system 
based upon the effects of the reactive hyperemia on the limb of patient. 
It is another object of the present invention to compare normal blood 
volume data and normal waveforms showing the pulsatile component of blood 
flow during substantially all of the reactive hyperemia episode with other 
data and waveforms from patients exhibiting healthy blood flow and 
cardiovascular disease and coronary artery disease in order to provide a 
noninvasive method and noninvasive system to measure coronary artery 
disease based upon the response and condition of the endothelium during 
reactive hyperemia. 
It is another object of the present invention to automatically perform a 
reactive hyperemia test on a plurality of patients and/or a number of 
reactive hyperemia tests on a single patient with a high degree of 
accuracy, precision and repeatability in order to reduce interpatient and 
intrapatient errors. This objective greatly enhances the creation of 
definitive studies among investigators. 
It is a further object of the present invention to provide measurements of 
pulse waveform and blood volume and to automatically gather that data with 
a minimum of error and bias. As explained herein, prior art techniques 
utilizing ultrasound machines and imaging techniques involve a 
considerable degree of operator intervention and hence, result in an 
unacceptable amount of operator error in the reported results. 
It is another object of the present invention to provide frequent and 
continuous measurement of the pulse volume response which enables 
detection of inter-test and/or interpatient differences, the magnitude of 
the responses that may be associated with the time-based phases of 
hyperemic response, i.e., the maximum response occurring in the early, 
mid-range, late or prolonged response. 
SUMMARY OF THE INVENTION 
The calibrated method for characterizing blood flow in a limb of a patient 
during reactive hyperemia utilizes a blood pressure cuff. The method 
establishes a predetermined, diastolic or near diastolic pressure in the 
blood pressure cuff during the reactive hyperemic episode, continually 
senses the pressure in said blood pressure cuff during the reactive 
hyperemic episode, and periodically changes the internal volume of said 
blood pressure cuff by a predetermined volumetric amount. This volumetric 
change establishes a calibration cycle. The method concurrently senses a 
resultant change in the pressure as a calibration pressure pulse and 
calculates pulsatile blood volume through the blood vessel by correcting 
the sensed pressure with the ratio of the predetermined volumetric amount 
and calibration pressure pulse. A calibrated method for determining the 
condition of blood vessels and endothelium includes determining, for each 
calibration cycle, a respective peak value for the blood volume, and 
comparing the peak blood volume values for the plurality of calibration 
cycles encompassing the reactive hyperemia episode with peak blood volume 
values for healthy blood vessels and endothelium during reactive 
hyperemia. The comparison is preferably made with acquired blood volume 
data or waveform and stored data or waveform showing peak blood volume 
values for healthy blood vessels and the characterization of the 
endothelium during reactive hyperemia. 
The calibrated system for characterizing blood flow includes a computerized 
electronic and pneumatic system which inflates, for a predetermined 
pre-test time, the blood pressure cuff to a suprasystolic pressure and 
thereafter establishes the diastolic or near diastolic pressure in the 
cuff during the ensuing reactive hyperemic episode. A sensor substantially 
continually senses the pressure in the cuff and generates a pressure 
signal, particularly a pressure pulse signal. A subsystem periodically 
changes the volume of the blood pressure cuff by a predetermined 
volumetric amount in a calibration cycle. A calibration pressure pulse 
signal is generated based upon a resultant change in the pressure signal. 
A blood volume signal is generated by correcting the sensed pressure 
signal with a ratio of the predetermined volumetric amount and the 
calibration pressure pulse signal. A calibrated system for determining the 
condition of blood vessels and endothelium includes the aforementioned 
elements and a computerized system for determining, for each calibration 
cycle, a respective peak blood volume value and for comparing the acquired 
peak blood volume values with a plurality of predetermined peak blood 
volume values representing healthy blood vessels and endothelium during 
reactive hyperemia. Typically, these are graphically presented and 
displayed as waveforms. Alternatively, data table presentations are 
provided to the operator.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The present invention relates to a calibrated measurement of blood vessels 
and endothelium after reactive hyperemia and a method therefor. 
Particularly, volume and flow through the arterial blood vessels is 
measured by the method and the apparatus. 
FIG. 1 diagrammatically illustrates the basic components of a computer or 
an electronic system 10 and a pneumatic system 12 used in connection with 
the calibrated measurement of blood vessels and the endothelium after 
reactive hyperemia. Due to the continual reduction in price, improvement 
in quality and integration of electronic and computer components, FIG. 1 
diagrammatically illustrates functional elements of the invention. 
Accordingly, the claims appended hereto are meant to cover the future 
integration of electronic components. Pneumatic system 12 includes a blood 
pressure cuff 14 that is adapted to be wrapped around the upper arm 16 of 
a patient. Particularly, since it is important to correctly locate cuff 14 
on upper arm 16, cuff 14 may include a label with written instructions 
instructing the operator to place cuff edge 18 a certain distance from 
elbow crease 20 of the patient's limb. The objective is to locate the 
cuff, on a regular basis, at a standard, specified and constant location 
or distance above the antecubital crease or fold. The pneumatic system 
described herein preferably utilizes a blood pressure cuff which is 
designated as the "standard" or predetermined cuff used for all the 
machines and used in connection with all methods described herein. The use 
of "standard" or a single type of cuff results in the establishment of a 
constant sized occlusion or blockage of the arteries in the limb of the 
patient. The relative dimensional sizes of the components in FIG. 1 are 
not accurate. As explained in detail later, cuff 14 is wrapped around 
upper arm 16, inflated for a 5 minute period to collapse the arteries and 
veins in limb segment 16, thereby achieving ischemia in the limb and the 
downstream portions of the limb. Blood pressure cuff 14 is inflated, 
deflated and controlled based upon pneumatic and electronic components on 
system board 22. System board 22 is explained in detail later in 
connection with FIGS. 2-4. 
The computer system 10 includes a keyboard or keypad 24 (and may further 
include a mouse, trackball or other pointing device, not shown), a main 
CPU box 26, a display screen or monitor 28, and a memory system 30. Memory 
system 30 includes hard drive 32, floppy drive 34, removable drive 36 and 
possibly a ZIP drive or comparable removable tape drive (not shown). A 
CDROM writer may also be used to write data to a CDROM. The computerized 
system 10 also includes a microprocessor 38, an input/output unit 40 and, 
in a preferred embodiment, a modem 42. The modem enables connection to the 
Internet. Input/output unit 40 may be connected to a computer network 44 
(local area network or wide area network) and/or a printer 46. 
Microprocessor 38 utilizes computer programs stored in memory 30, which 
includes hard drive 32, floppy drive 34 and removable drive 36, as 
necessary, as well as random access memory RAM and readonly memory ROM 
(included in memory 30). The microprocessor obtains, processes and stores 
data with the assistance of the memory 30 and under the control of 
programs stored in memory 30. Microprocessor 38 controls various 
peripheral equipment via input/output unit 40. These peripherals include 
display 28, modem 42, printer 46 and network card or board 44. The 
input/output unit 40 also controls keyboard 24 and any associated mouse or 
other operator input control. Microprocessor 38 is connected to these 
various electronic components and to the system electronic/pneumatic unit 
22 via a bus 48. 
FIGS. 2-4 diagrammatically illustrate various pneumatic and electronic 
systems to measure the dilation of blood vessels and actions of the 
endothelium with reactive hyperemia as well as to create the reactive 
hyperemia in the patient's limb. FIG. 2 diagrammatically illustrates the 
preferred embodiment. However, the systems in FIGS. 3-4 may be utilized to 
achieve substantially the same results. 
In FIG. 2, a pump P 50 is pneumatically connected to valves 52 and 54 via 
line or tube 77. Main valve 52 is pneumatically connected via line 83 to 
blood pressure cuff coupling 56. Pressure sensor 58 is also pneumatically 
linked to line 77, pump 50 and valves 52, 54. Sensor 58 monitors the air 
or other pressure in the blood pressure cuff system. This pressure sensor 
substantially continually monitors pressure based upon a pre-programmed 
sampling rate. Although unlikely, a hydraulic system may be utilized 
rather than a pneumatic blood pressure cuff system. This hydraulic 
embodiment is unlikely because of the wide acceptance of pneumatic blood 
pressure cuff systems by the medical community. 
Main valve 52 has a primary pneumatic output that is further pneumatically 
linked to a resistive pneumatic element 59. The positioning of main valve 
52 may be changed such that resistive element 59 is at its input. Piston 
system 60 is pneumatically coupled at an intermediate position relative to 
resistive element 59 and secondary valve 54. Piston system 60 includes 
piston head 62 which is biased forward by spring 64 mechanically acting on 
stop 66. The face of piston 62 effects the volume of chamber 68 in piston 
system 60. The backside of piston head 62 is effected and acted on by the 
air pressure in the backside chamber 69. This air pressure in backside 
piston chamber 69 is controlled by secondary valve 54 which is 
pneumatically linked to the backside of the chamber. 
Main valve 52 and secondary valve 54 both include exhaust ports 53, 55. 
Ports 53, 55 may be quick action valves. 
Pump 50, main valve 52 and secondary valve 54 are controlled by electronic 
signals supplied by and supplied through signal conditioner 70. Signal 
conditioner 70 is an interface between the valves and the balance of the 
electronic system. The signal conditioner 70 may be incorporated into the 
other electronic devices or may include several discrete electrical 
components. The pump drive signals and valve control signals are generated 
by a microcontroller 72 in accordance with programs stored in memory 74. 
Memory 74 may include random access memory, read only memory or may be 
incorporated into computer system memory 30. Further, microprocessor 72 
and memory 74 may be replaced with programmable logic or erasable 
programmable read only memory (EPROM) or programmable read only memory 
(PROM) as appropriate. In the preferred embodiment, the electronic and 
pneumatic system board 22 includes an on-board microprocessor and an 
on-board memory in order to generate pump control and valve control 
signals via signal conditioner 70 to main valve 52, pump 50 and secondary 
valve 54. 
Pressure sensor 58 is electronically monitored by analog to digital A/D 
converter 76. The output of A/D converter 76 is connected to 
microprocessor 72 and memory 74 and also to the main computer bus 48. It 
should be noted that microprocessor 72 and memory 74 may be replaced by 
and integrated with main microprocessor 38 and memory 30 in computer 
system 10. This integration may depend upon the speed of microprocessor 38 
and multi-tasking capability of that microprocessor as well as the cost of 
an on-board microprocessor 72. Pressure data signals may be temporarily 
stored in on-board memory 74 dependent upon the architecture of the 
electrical hardware and software. 
In operation, the electronic and pneumatic system illustrated in FIG. 2 
operates in the following manner. Main valve 52 closes. Secondary valve 54 
is opened and exhausts any pressure in pneumatic lines 77 and 79 by 
venting the subsystem to the ambient pressure environment via exhaust port 
55. Secondary valve 54 then closes and pump 50 is activated. Main valve 52 
is opened. Pump 50 is commanded to inflate cuff 14 (FIG. 1) to a 
suprasystolic pressure level which effectively collapses or occludes all 
the arteries in the upper arm 16 of the patient. A suprasystolic pressure 
is a pressure greater than the patient's highest level of blood pressure 
in his or her vascular system. In one working embodiment, the 
supra-systolic pressure is 20 mmHg above the previously obtained systolic 
pressure of the patient. The pressure in the pneumatic system (pneumatic 
line 77 and cuff 14) is substantially continually monitored by sensor 58, 
A/D converter 76 and ultimately microprocessor 72. A duplicate monitoring 
of the pressure signal may be implemented with main processor 38. In the 
event of a failure (mechanical, pneumatic or patient voluntary or 
involuntary interruption), microprocessor 72 stops pump 50 and opens main 
valve 52 and/or secondary valve 54 thereby venting pressure from the 
pneumatic system (line 77 and cuff 14) via exhaust port 55 and/or 53. 
During normal operation, pump 50 is activated to pump up and pneumatically 
inflate cuff 14 until all the arteries in limb 16 collapse thereby 
blocking any blood flow through those arteries into the downstream portion 
of limb 16. 
This condition is maintained for 5 minutes to achieve ischemia or extreme 
hypoxia in the patient's limb. This is a predetermined pre-test time 
period which is a standard used by most clinical investigators. This time 
may be shortened or lengthened based upon further experimentation. Pump 50 
is turned OFF when pressure sensor 58 (and associated electronics) detects 
a predetermined suprasystolic pressure level in the pneumatic blood 
pressure cuff system (line 77, 83 and blood pressure cuff 14). The 
suprasystolic pressure level is generally specified at a level 20 mmHg 
above the subject's systolic pressure but other elevations may be used. 
When the pneumatic blood pressure cuff system reaches the suprasystolic 
pressure (established either by (a) a predetermined value programmed into 
microprocessor 72 and memory 74 or programmed into main microprocessor 38 
and memory 30 or (b) a predetermined level above the patient's systolic 
pressure), a timer or clock is initiated in the appropriate memory under 
the control of the appropriate microprocessor. Currently, the timers are 
maintained by main microprocessor 38 and memory 30. Upon the expiration of 
the predetermined time period (5 minutes), microprocessor 72 and memory 74 
(under the ultimate control of main microprocessor 38 but the specific 
control of processor 72 ) commands main valve 72 to open its exhaust port 
53 to quickly release pressure from the pneumatic system established by 
blood pressure cuff 14. 
This quick release feature is one feature of the present system. An 
additional quick release exhaust valve may be added to the system if 
necessary (not illustrated). The further quick release system would be 
pneumatically coupled on line 83. The electronic output of pressure sensor 
58 is monitored by microprocessor 72 until the pressure reaches the 
diastolic level or a near diastolic level. This quick release of cuff 
pressure is required in order to rapidly achieve reactive hyperemia in 
limb segment 16 and the downstream portions of that limb segment. As 
described in greater detail hereinafter, the calibrated system and the 
calibrated method in accordance with the principles of the present 
invention periodically calibrate the pneumatic system while acquiring 
pressure wave pulse data during reactive hyperemia. 
The predetermined diastolic or near diastolic pressure level at which main 
valve 52 (or alternately valve 54) closes is determined in whole or in 
part upon the patient's diastolic or low blood pressure level. In one 
working embodiment, the predetermined pressure is 5 mmHg less that the 
measured diastolic pressure. Prior to initiating the test described 
herein, the medical professional obtains, via conventional methods or 
otherwise, the patient's diastolic (low level) and systolic (high level) 
blood pressures. A typical diastolic/systolic blood pressure (BP) is 
120/60 mmHg. Normal systolic pressure in the range of 90-140 mmHg is 
reasonable. Diastolic pressure of 60 mmHg plus or minus 10 mmHg is 
reasonable. Since the diastolic pressure should be about 60 mmHg, the 
presently described system may be pre-set to close the exhaust valve 
during the quick release operational module at 60 mmHg. However another 
version, the system operator may be prompted to (a) obtain the patient's 
diastolic/systolic blood pressure/(BP); and (b) input that BP data into 
the system. In this event, the system may utilize the input diastolic 
pressure plus or minus a pre-set value (e.g. 5 mmHg) rather than the 
pre-set pressure of 60 mmHg. The term "near diastolic" is meant to cover 
these three variations. 
In a further enhancement, the system may be configured to directly measure 
both BP data points prior to initiating reactive hyperemia in the patient. 
Electronic systems controlling and monitoring pneumatic systems to acquire 
and store diastolic and systolic blood pressure data are known in the 
biomedical industry. In a working embodiment, (a) the operator measures BP 
via conventional audio methods, (b) the operator inputs this data into the 
system, (c) the system inflates the cuff to 5 mmHg less then the measured 
diastolic pressure, (d) calibrates the data, (e) measures and computes 
V.sub.m and Q.sub.p (discussed later herein) and (f) then occludes the 
artery and initiates the hyperemia reactive test described in detail 
hereinafter. 
Either of these pre-test procedures may be utilized to obtain, record and 
utilize a diastolic pressure level, or a pre-set value offset from 
diastolic pressure, as a predetermined base cuff pressure level. As 
explained later, the predetermined base pressure is easily convertible 
into a predetermined base blood volume level V and a predetermined base 
blood flow level Q. The term "level" as used herein is equivalent to the 
terms "data" or "value." The term "limb" or "arm" can refer to any of the 
body's limbs. 
The system and method may also be modified to measure the physiologic 
condition of the blood vessels by monitoring blood pressure, pressure 
pulses, and hence blood volume, at a predetermined level above or below 
the patient's diastolic pressure (e.g. diastolic minus 5 mmHg.). 
Returning to a brief description of the operation of the calibrated system 
and method, during each calibration cycle, secondary valve 54 is opened to 
vent pneumatic line 79 and exhaust the pressure from line 79 through 
exhaust port 55. Valve 54 may be able to independently vent line 79 
separate from line 77. When the pressure is vented from pneumatic line 79, 
the pressure is reduced in back chamber 68 of piston unit 60. 
At an earlier time, pneumatic line 79 and back chamber 69 held the same 
pressure as pneumatic line 77 and blood pressure cuff subsystem 14. 
At the calibration trigger time, established by microprocessor 72 and 
memory 74 (optionally processor 38), secondary valve 54 vents pneumatic 
line 76 to the ambient environment via exhaust port 55. This also vents 
the pressure from back chamber 69. Piston head 62 then moves backwards 
against the biasing force of spring 64 a predetermined volumetric amount. 
Rearward movement of piston head 62 is caused by the pressure differential 
between chambers 68 and 69 (lines 81-83 and 79). This predetermined 
movement changes the internal volume in the pneumatic system (established 
by pneumatic lines 81, 83 and blood pressure cuff 14) by a predetermined 
volumetric amount. The biasing force of spring 64 and the movement of 
piston head 62 within chambers 68, 69 is carefully preset such that when 
piston head 62 moves and expands chamber 68, the expansion increases the 
volume of the pneumatic system (lines 81, 83 and pressure cuff 14) a 
predetermined volumetric amount. In a currently preferred embodiment, the 
volume change in the pneumatic system is 0.68 ml. Volume is added to the 
cuff system. In a different embodiment, volume may be subtracted from the 
cuff system by forcing piston head forward in chamber 68. 
As explained in detail later, this volumetric calibration amount V.sub.cal 
is added at several times during the reactive hyperemia episode to the 
cuff system in order to recalibrate the system pursuant to realtime 
derived timing requirements. The timing requirements are keyed to the 
sensed pressure pulses. Frequent recalibration of the system is thought to 
be necessary for optimal accuracy and precision while repeatedly measuring 
small changes in the pressure pulse waveform. The pneumatic and electronic 
data acquisition system may drift thereby corrupting the data acquisition 
and processing. The system measures blood pressure pulse changes. More 
specifically, the system responds to blood pressure pulse volume changes 
in the arterial system in the patient's limb. Typically, the diameter of 
the brachial artery in an arm changes 1.3% to 6.2% during these blood 
pressure pulses. 
Periodic recalibration avoids and eliminates the problems regarding 
pneumatic and electronic signal drift. Also, it has been established by 
preliminary testing that the response and the performance of the pneumatic 
system changes (a) during the hyperemia test (i.e., over time); (b) based 
upon the cuff pressure in the pneumatic system and (c) due to pneumatic 
and mechanical limitations in the current equipment. For example in one 
working embodiment, it is not possible to precisely and continuously 
maintain diastolic or near diastolic (5 mmHg below diastolic) pressure in 
the pneumatic system for 5-10 minutes hyperemic episode. This "leakage" or 
pneumatic drift may be due to many factors (e.g., the specific cuff used 
in the present experiments, the cuff's linkage to the pneumatic coupler on 
the PC board, the pneumatic system mounted on the PC board (unlikely, but 
possible), the type or quality of valves, pump or calibration cylinder 
used on the PC board). Some of these factors may be eliminated by 
improving the quality of the components or improving the interfit or 
mechanical interfaces between the components. However, it is unlikely that 
all pneumatic drift (presently on the order of about plus or minus 2-5 
mmHg over five to ten minute hyperemic time frame) will be eliminated. 
Even if such drift is reduced by closer manufacturing tolerances and 
quality assurance programs, the projected high utilization rate of the 
machine (7-10 patients per day) and life cycle durability of the machine 
(grossly currently estimated at 3-5 years), it is inevitable that the 
"wear and tear" on the machine will cause pneumatic signal drift. Frequent 
and repeated calibrations during the RHT test significantly reduce, if not 
eliminate, this drift problem since pulse signals are captured based upon 
calibration triggers. 
In U.S. Pat. No. 5,718,232 to Raines, et al., it is known that at each 
discrete induced cuff pressure level (50 mmHg, 60 mmHg, 70 mmHg . . . 120 
mmHg), the pneumatic system provides a slightly different response to the 
blood flow through the patient's arteries (measured by blood pressure 
pulse data) than at other pressure cuff levels. The system response at 60 
mmHg is different than the system response at 90 mmHg. 
In the present invention, it is thought that since the response of the 
brachial arterial diameter during reactive hyperemia diminishes from 6.2% 
(a healthy arterial diameter response) to 1.3% (a diseased arterial 
diameter response), the periodic calibration of the pneumatic system 
measuring blood pressure pulse waves is necessary to obtain correct blood 
volume pulse wave data V during the entire 5-10 minute reactive hyperemia 
episode. The episode may last 10 minutes and the calibrated testing method 
described herein can be easily expanded to cover the longer 10 minute RHT 
test. 
Further, the utilization of the internal calibration system described and 
claimed in connection with the present invention enables the medical 
community to gather blood volume pulse data and waveforms in a 
standardized, constant, reproducible and an automatic manner. By acquiring 
this blood volume pulse wave data utilizing standard calibration 
techniques, both repetitive calibration during the reactive hyperemia 
episode and the standardized nature of the calibration (withdrawing or 
injecting predetermined volumes from the pneumatic cuff system), further 
measurements of brachial artery dilation and performance and condition of 
the endothelium can be reproduced with different patient groups at many 
medical facilities by many researchers. The standardized collection of 
data will greatly advance the study of NO, endothelial reaction and blood 
vessel activity during reactive hyperemia. 
One of the major drawbacks in the study of the health and condition or 
physiologic characterization of the endothelium and the effects of nitric 
oxide NO is the utilization of ultrasound data. Ultrasound techniques 
measure the diameter of the brachial artery during reactive hyperemia. As 
discussed in detail above, ultrasound data include operator errors, visual 
data acquisition errors and interpretation errors. The present data 
acquisition system is better for several reasons. Operator error is 
minimized because the instructions are on the cuff label and use of the 
method and the machine is simplified. Hand-eye coordination to acquire an 
image signal is eliminated. Operator placement of electronic calipers 
about an electronic ultrasound image to measure arterial diameter is 
eliminated. Lastly, blood volume change is directly measured without 
resort to visual measurements and compounding computational errors. Also, 
the present invention is absolutely non-invasive. 
Since the present invention establishes an automatic and standardized 
calibration routine with volume additions or subtractions from the 
pneumatic system and periodic automatic calibration of the acquired 
signals during the entire reactive hyperemic episode, the study of the 
health, condition and physiologic characterization of the endothelium, the 
effects of NO, and the effects of drugs on NO and on the cardiovascular 
system can be easily standardized. Therefore, data can be shared among 
researchers to compare and contrast the effectiveness of drugs, the 
effects of lifestyle modifications, the cessation of smoking, and the 
effects of diet on the endothelium and the cardiovascular system. These 
are major objectives of the invention and a summary of the problems solved 
by the invention described herein. 
FIGS. 3 and 4 diagrammatically illustrate other types of pneumatic systems. 
In FIG. 3, pump 50 is pneumatically connected to pneumatic line 90. 
Pressure sensor 92 is electronically connected to A/D converter 76 and is 
pneumatically connected to pneumatic line 90. Safety relief valve 94 
insures that, if an adverse or other undesirable event occurs in the 
testing procedure, safety valve 94 opens and quickly vents the pressure in 
the pneumatic system to the ambient environment. Quick release valve 96 is 
utilized to quickly vent air from the pneumatic system which includes 
pneumatic line 90 and blood pressure cuff 14. The system is vented via 
exhaust 97. Valves 98 and 99 are utilized to add a predetermined volume 
into the pneumatic system. This predetermined volume is established by 
pneumatic chamber or line 95. 
Briefly, when the pneumatic and electronic system is operating during the 
reactive hyperemia episode and the system is collecting blood pressure 
pulse wave data (see FIG. 10), the calibration steps include (a) opening 
valve 99 and exhausting the pressure in pneumatic line 95 while valve 98 
is closed; (b) closing valve 99; (c) opening valve 98 at the calibration 
time thereby exposing the volume in chamber 95 (a calibrated volume 
V.sub.cc) to the pneumatic system which includes pneumatic line 90 and 
blood pressure cuff 14; (d) detecting the pressure change P.sub.CAL with 
sensor 92; (e) computing the corrected blood volume pulse waveform based 
upon the ratio of the predetermined volume V.sub.cc added to the pneumatic 
system and the measured pressure calibration data P.sub.CAL and taking 
that ratio into account when computing the blood volume pulse waveform 
V.sub.n with the current diastolic pressure P.sub.d established as a base 
line. This computation of the blood volume pulse waveform is discussed in 
detail later. 
FIG. 4 diagrammatically illustrates another embodiment of the pneumatic and 
electronic system. In this embodiment, pump motor control 70 is coupled 
motor 103a which is coupled to a positive displacement pump output 101 
(the entire unit may be called a positive displacement pump) which is 
connected to pneumatic line 103. Pneumatic line 103 is connected pressure 
sensor 58 and main valve 52. Cuff coupler 56 is pneumatically and 
mechanically connected to blood pressure cuff 14. Main valve 52 has an 
exhaust port 53 and is electronically connected to valve control 70. 
In operation, motor 103a drives positive displacement pump output 101 to 
initially pump up and achieve the correct air pressure in the pneumatic 
system which includes pneumatic line 103 and blood pressure cuff 14 (first 
supersystolic, then quick release, then diastolic pressure). In order to 
achieve calibration of the system, positive displacement pump output 101 
is triggered to inject a predetermined volume V.sub.cc into the pneumatic 
system. The output of PDP pump 101, on line 103 is a predetermined volume 
of air. In a preferred embodiment, this injected volume is 1 ml. Sensor 58 
then detects the change in the system pressure P.sub.cal and this 
calibrated pressure pulse p.sub.cal is utilized to compute the actual 
blood volume pulse waveform V.sub.n numerous times over a time period 
which includes the reactive hyperemia episode. 
FIG. 5 diagrammatically illustrates some of the arterial system in limb 16 
of the patient. FIG. 5 will be discussed concurrently with FIGS. 6a, 6b 
and 6c which diagrammatically illustrate the ischemia and subsequent 
dilation of the brachial artery during reactive hyperemia. 
In FIG. 5, brachial artery 110 will be compressed and collapsed about 
region 112 by a compressive force placed about limb 16 (FIG. 1) of the 
patient with blood pressure cuff 14. Region 112 is upstream of the 
brachial arterial branch 114 (near the patient's elbow crease). In FIG. 
6a, brachial artery 110 is diagrammatically illustrated beneath epidermis 
skin layer 116. At rest and in a sedentary position, brachial artery 110 
of the patient has a diameter d.sub.1. 
In order to establish and record pressure pulse data and waveforms and 
calculate calibrated blood volume pulse data and waveforms, the patient 
should undergo certain pre-test preparations, be placed in a certain 
position and maintained in a certain condition during the test. In a 
preferred embodiment, the pre-test and test conditions will be specified 
in a defined and a standardized manner to establish a certain medical 
protocol. The following Pre-Study Patient Condition Table provides some 
examples, of a fundamental nature, of the condition of the patient prior 
to conducting the test to determine the state or condition of the 
endothelium with reactive hyperemia. 
Pre-Study Patient Condition Table 
patient sedentary and in a relaxed state 
no food for more than 2 hours (possibly 12 hours) before test 
no coffee or caffeine beverages for more than 1 hour before test 
no smoking for more than 1 hour before test 
It has been established by other researchers that if a patient eats a high 
fat meal, e.g., a MC DONALD'S BIG MAC, within one hour prior to an 
ultrasonic test to measure brachial arterial diameter during reactive 
hyperemia, the patient's arteries, and hence the data, is adversely 
affected by the high amount of salt, dietary fat and cholesterol. 
Other factors affect the condition of the endothelium and the generation NO 
by the endothelium and the dilation of the patient's cardiovascular 
system. The following table lists typical factors. 
Factors Affecting Endothelium and NO Generation 
age 
gender 
smoking 
plasma cholesterol level 
disease (especially coronary artery disease and peripheral vascular 
disorders) 
With the acquisition of calibrated blood volume pulsatile data, researchers 
may identify other factors which affect the response of blood vessels and 
the endothelium during reactive hyperemia. 
The following Physiological Process Table provides a general outline of the 
physiologic effects of reactive hyperemia on the endothelium and the 
cardiovascular system of a patient as currently understood by one of the 
inventors. 
Physiological Process Table 
1. cause anoxia or severe hypoxia in the limb's arterial system 
2. which causes an increase in NO production by the arterial endothelium 
3. which results in dilation of the local and distal arterial system 
4. which is believed to cause a reduction in peripheral resistance in the 
resistive vessel muscles 
5. which is generally believed to cause an increase in pulsatile blood flow 
(Q) 
6. which causes a further increase (potentially) in pulsatile blood flow 
(Q) (which increase may be small or not measurable) 
In summary, FIG. 6b shows the collapse of brachial artery 110 by blood 
pressure cuff 14. The illustrated force is shown by arrows 117. In a 
preferred embodiment, ischemia in the patient's limb is established for 5 
minutes. In FIG. 6c, blood pressure cuff 14 has been quickly released and 
brachial artery 110 has expanded to diameter d.sub.2. Even though 
significant suprasystolic pressure has been released from blood pressure 
cuff 14, pressure cuff 14 exerts a small pressure 119 (diastolic or near 
diastolic) on the limb 16 in order to capture physiological data regarding 
the pressure pulse waveforms at the predetermined diastolic pressure. 
Hence, force vector arrows 119 are smaller than vector arrows 117. 
FIGS. 6a-6c are related to FIG. 5 in the following manner. Upon collapse 
the brachial artery 110 due to a suprasystolic pressure placed on region 
112 about limb 16 of the patient, the downstream portions of the limb 
experience anoxia or severe hypoxia. When the suprasystolic pressure is 
released from the blood pressure cuff 14 (but maintained at or near 
diastolic pressure), there is a reduction in the peripheral resistance of 
the resistive blood vessel muscles 120 located in distal regions of the 
patient's limb, diagrammatically illustrated in FIG. 5. These resistive 
vessel muscles 120 are primarily located in and about the arterials 122. 
The relaxation of the resistive vessel muscles 120 causes an increase in 
pulsatile blood flow (identified herein as Q), and an increase in the 
generation and transmission of nitric oxide (NO) through the endothelium. 
This NO or chemical composition biomaker is generated throughout the 
endothelium and travels therethrough from arterials 122 upstream to a 
point about critical monitoring area 112 of brachial artery 110. The NO 
causes dilation of the arterial system primarily due to a relaxation of 
the resistive vessel muscles 120, an increase in pulsatile blood flow Q 
and a possible further increase in pulsatile blood flow. This last 
increase (step 6 in the Physiological Process Table) may not be 
measurable. However, it is apparent that a careful measurement of arterial 
blood vessels slightly upstream of the brachial arterial branch 114 (near 
the patient's elbow crease) provides a very good indication of the health 
or the condition of the endothelium, the generation and transmission of NO 
and the health of the cardiovascular system during reactive hyperemia. 
The present invention measures the production of NO and the condition of 
the blood vessel and endothelium about the entire limb 16 rather than 
simply measure the diameter of the brachial artery 110 as is currently 
done by ultrasound techniques. 
The prior art systems utilizing ultrasonic imaging only focus on the change 
in diameter of brachial artery 110 during reactive hyperemia. This change 
in diameter d.sub.1 to d.sub.2 (FIGS. 6a, 6c) is on the order of 0.30 to 
0.33 mm. Healthy patients without cardiovascular disease present an 
increase in brachial arterial diameter of approximately 6.2% during 
reactive hyperemia. Another group of patients having a history of coronary 
artery disease show an increase in brachial artery diameter of 1.3%. 
Accordingly, the sensitivity of the present invention, the ability of the 
present invention to automatically initiate a quick cuff release, and the 
standardization of the calibration pulse and the periodic calibration of 
the data acquisition system during the entire reactive hyperemia episode, 
all contribute to the benefits achieved by the present invention over the 
pre-existing technology. These benefits are apparent because of the small 
change (approximately 0.30 mm) of the brachial artery during reactive 
hyperemia. Other clinical studies using prior art technology have revealed 
that the response of the endothelium and the generation of NO can be 
directly correlated with the presence or absence of coronary artery 
disease. Since the present invention is a noninvasive method and system 
for detecting the onset and degree of coronary artery disease, the present 
invention is potentially better suited technically and practically than 
other invasive methods to detect coronary artery disease. Other invasive 
methods to detect these problems include cardiac catheterization and 
angiographic procedures. 
FIG. 7 diagrammatically illustrates a plot or a chart of either blood 
volume V or blood flow Q versus time t. At time T1, the patient's limb is 
compressed and the limb experiences ischemia or extreme hypoxia (a 5 
minute period). At time episodic period T.sub.2, the system first 
initially quickly releases the pressure in blood pressure cuff 14, the 
pneumatic and electronic pressure sensing system settles to a 
predetermined diastolic pressure, the patient's limb and arterial system 
generates NO and provides initial stage data of the reactive hyperemic 
episode. Time period T.sub.2 may last up to 1 minute. This is the first 
stage of the reaction. In time T.sub.3, the system continues to measure 
the reactive hyperemia episode and detects the condition of the 
endothelium and the generation of NO through the cardiovascular system. 
The initial or primarily significant data acquisition period is the first 
5 minutes after cuff pressure release (T.sub.2 plus T.sub.3). The 
subsequent 5 minute period T.sub.4 captures the secondary phase data of 
the reactive hyperemia test (RHT Test). 
______________________________________ 
Reactive Hyperemic Time Table 
______________________________________ 
T.sub.1 five (5) minutes to achieve ischemia or 
extreme hypoxia 
T.sub.2 about one (1) minute for physiological system to 
initiate first stage of reaction 
T.sub.2 plus T.sub.3 
about five (5) minutes to monitor typical, primary 
phase of reactive hyperemia episode 
T.sub.4 about five (5) minutes to monitor typical, secondary 
phase of reactive hyperemia episode 
T.sub.2 plus T.sub.3 plus T.sub.4 
about ten (10) minutes 
______________________________________ 
Utilizing ultrasound prior art techniques, the ultrasound operator, in the 
first minute after cuff release, visually identifies and locates the 
brachial artery and prepares himself or herself for the data acquisition 
imaging phase. In the subsequent 60 second period, the ultrasound operator 
captures the image of the greatest expansion of the diameter of the 
brachial artery. This image acquisition period generally corresponds to 
the peak of the blood flow waveform shown in FIG. 7. In the third 60 
second period subsequent to cuff release, the operator watches the 
diameter of the brachial artery decrease. Since the diameter of the artery 
reduces in size, there is a decrease in blood flow. Of course, in the 
ultrasound data acquisition system, the operator only sees the change in 
arterial diameter (on the order of 0.30 mm). The ultrasound operator does 
not measure the change in blood flow. He or she measures arterial diameter 
change. However, this blood flow change is apparent in the sonic image 
because of the visually confirmed change in arterial diameter. 
The present invention actually monitors and captures pressure pulse data 
and waveforms P.sub.t in real time and converts them to calibrated blood 
volume pulse data and waveforms V.sub.n with periodic calibration pulses. 
This direct measurement of blood volume V and blood flow (Q) is a 
significant difference between the ultrasound systems and the present 
invention. 
FIG. 8 diagrammatically illustrates a plot or a graph of the pulsatile 
component of blood flow Q.sub.p versus episode time t. Essentially, the 
present invention captures pressure waveform P.sub.t data, converts that 
pressure waveform data into blood volume pulse V.sub.n data (per a 
calibration routine) and then, in one embodiment, samples periodic blood 
volume data (preferably obtaining the maximum or peak value V.sub.m of 
selected, periodic waves V.sub.n). The peak value of blood volume V.sub.m 
in relation to episodic time is one type of measurement to show the 
condition of the blood vessel. Another measurement is the resulting 
calculation of pulsatile blood flow Q.sub.p. FIG. 9 is blood flow plotted 
data. In this embodiment in FIG. 8, the height or peak m of the blood 
volume pulsatile signal V is plotted versus episode time t. At time 
t.sub.1, the blood pressure cuff has been released, the system is settled 
(about 20 seconds) and data acquisition begins. A settling period may be 
necessary due to the pneumatic quick release of air pressure. A plurality 
of blood volume peak data points V.sub.m are obtained and plotted and 
mapped. Mapping may be to a data table (V.sub.m and episodic time) or 
graphically stored (V.sub.m versus t). At time t.sub.2, the maximum blood 
volume peak V.sub.m is computed by the system and preferably displayed to 
the operator, health professional or physician. At time t.sub.3, the 
patient's cardiovascular system has reached the end of the reactive 
hyperemia episode. 
In FIG. 8, the plot of V.sub.m with respect to time t may not be absolutely 
precise. The reactive episodic time t may be replaced by pulse wave number 
n. In other words if the patient has a heart rate of 60 beats per minute 
and the test lasts 3 minutes (a short version of the test), 180 blood 
pressure waves or data are available. The signal settle period may be one 
minute. Sixty (60) waves are discarded at initial settling stage period 
T.sub.1. As explained later, six (6) wave cycles are utilized for each 
calibration window or cycle. As an alternative embodiment, three (3) of 
the six waves in each calibration window are averaged to reduce motion 
artifacts. In one initial working embodiment, only one wave or data value 
from each calibration cycle is initially utilized. Accordingly from the 
120 wave segment (180 waves less 60 waves for signal settling), 20 
corrected wave signals or data V.sub.n are available. The peak values 
V.sub.m are computed. Since the patient's heart rate may not be precisely 
60 beats per minute (it may be 59, 62, 58), the system may plot V.sub.m 
versus pressure or volume wave number 61, 67, 74, 81, 88, 95. . . etc. In 
a working embodiment, V.sub.m versus episodic time is mapped to a data 
table and to a graphic, waveform display. Blood flow Q.sub.p is calculated 
by (a) integrating the V.sub.n pulsatile waveform with respect to time 
(after the signal settling period), adding the integrated signal data and 
dividing the sum by a standard time period (the result being flow Q.sub.p 
in ml per minute). 
However, FIG. 8 is accurate with respect to blood volume flow Q.sub.p 
versus episodic time t if time t is measured from the quick cuff release 
time. In this event, there is a "discontinuity" in the graph because the 
graph in FIG. 8 does not show ischemia time T.sub.1 (FIG. 7). Further, 
time t.sub.1 begins at time period T.sub.2 in FIG. 7. Time is also 
discontinuous in FIG. 7. Since the physician or health professional is 
primarily interested in the V.sub.m data and the shape, height, size and 
other waveform characteristics of V.sub.m from time t.sub.1 to time 
t.sub.3 and the time t.sub.4, the time-based discontinuity due to ischemia 
is not significant. If wave number is used rather than time, no 
discontinuity would be present. 
With respect to FIG. 8, a basal blood flow level Q.sub.p has been 
established based upon the calibrated and summed blood volume pulsatile 
data. This basal level is obtained prior to initiating a reactive 
hyperemia in the patient's limb. The basal blood volume level is also 
obtained electronically prior to the test. V.sub.m is the peak value of 
the corrected blood volume pulse wave V.sub.n at predetermined times. In 
an initial working embodiment, five V.sub.m data points are acquired, 
calibrated, processed and calculated from the pulsatile pressure wave data 
during the 60 second period after a 20 second signal settlement period 
(after t.sub.1). The signal settlement period may be adjusted as necessary 
to match equipment limitations. Shorter settle periods are preferred. An 
additional seven V.sub.m data points or values are obtained and processed 
during the remaining portion of the five minute reactive hyperemia test 
(short RHT test). For example, V.sub.m data is obtained at about 110 
seconds after release, at 140 seconds, 170 seconds, 200 seconds, 230 
seconds, 260 seconds, and 290 seconds after release of t.sub.1 (FIG. 8). 
Data tables for V.sub.m at those times are mapped electronically by 
waveform data acquisition and processing techniques. 
In FIG. 9, the pulsatile component of blood flow Q.sub.p versus episodic 
time t for several patients is plotted atop each other. Essentially, FIGS. 
8 and 9 show individual and collective recovery profiles for reactive 
hyperemia tests, respectively. These recovery profiles or recovery 
waveforms W provide good physiological data regarding the health or the 
condition of the endothelium, the generation of NO by the patient and the 
cardiovascular health of the patient. 
Ultrasound studies have established that if patients with cardiovascular 
disease utilize nitroglycerin, this increases NO in the patient's system 
and the expansion of the brachial arterial diameter during reactive 
hyperemia changes from 3.78 mm to 3.89 mm. Accordingly, the recovery 
profile waveforms in FIGS. 8 and 9 also provide an indication of the 
effectiveness of drugs, e.g. nitroglycerin, in the patient as well as the 
generation of NO and the transmission of NO through the arterial bed. 
It has been proposed, based upon the present invention, that the recovery 
waveform profiles w.sub.1, w.sub.2, w.sub.3 and w.sub.4 shown in FIG. 9 
mostly likely show a normal state (waveform w.sub.1), a rapid recovery 
(waveform w.sub.2), a diminished recovery (waveform w.sub.3), and a 
diminished prolonged recovery (waveform w.sub.4). Of course, deviations or 
changes from the normal recovery profile waveform w.sub.1 provide an 
indication of the health and condition of the cardiovascular system of the 
patient under study. 
______________________________________ 
Exemplary Waveform Classification Table 
______________________________________ 
W.sub.1 normal recovery profile 
W.sub.2 rapid recovery 
W.sub.3 diminished recovery 
W.sub.4 diminished and prolonged recovery 
______________________________________ 
Further, the recovery profile waveform may be analyzed with various 
mathematical algorithms. For example, the researcher could compare the 
sequential calibrated blood volume pulse waveform V.sub.n at 30 second 
intervals after signal settlement period (for a 3 minute reactive 
hyperemia episode, 6 blood volume pulse waveforms V.sub.n are studied 
inclusive of initial stage T.sub.1 but after signal settlement) and review 
the rise and fall of the peak values V.sub.m for the six waveforms. 
Running averages of blood volume pulse waveforms (e.g. computing a three 
(3) wave average V.sub.n -Ave during successive six wave calibration 
periods) could be taken and compared against each other. The researcher 
could average three waveforms V.sub.n -Ave prior to the calibration pulse 
(in a six wave calibration cycle) and analyze the running peak values 
V.sub.m -Ave over the 3-5 minute reactive hyperemia episode. Further, the 
waveforms could be utilized with weighted average (based on time t from 
initial stage T.sub.1) to compare the blood volume data V.sub.m with 
respect to episodic time. Blood flow Q.sub.p at different episodic times 
may be compared. The following Waveform Analysis Table may provide some 
guidance. 
______________________________________ 
Waveform Analysis Table 
______________________________________ 
periodic, selected peak values or data V.sub.m 
running average peak values, e.g., average 3 V.sub.m (V.sub.m - Ave) 
episode 
analysis, use V.sub.m - Ave as data points V.sub.t, V.sub.t2, V.sub.t3, 
V.sub.tn 
weighted average calculations of V.sub.tn based on time of acquisition 
leading slope of V.sub.tn (or trailing slope) at selected episodic times 
t.sub.1 t.sub.2 
leading slope V.sub.rm or Q.sub.p (or trailing slope) during episode 
gross value of slope (peak V.sub.rn or Q.sub.p versus time from base to 
peak (t.sub.1 -t.sub.2)) 
integrated value of corrected V.sub.a waveform (from t.sub.1F to 
t.sub.1B) (FIG. 10) 
integrated value of V.sub.m and/or Q.sub.p waveform (FIG. 8) 
first, second or third derivatives of V.sub.m waveform or Q.sub.p at 
selected 
episode times. 
______________________________________ 
FIG. 10 diagrammatically illustrates one method for calibrating the blood 
pressure pulse wave P.sub.t and generating and calculating blood volume 
pulse waveform V.sub.n. 
In lower region 210, the system displays (on a monitor) pressure pulse 
waveforms P.sub.t. At a time prior to t.sub.0, the system experiences 
discontinuities and transients due to pneumatic and electronic settlement 
based on the quick release of pressure from blood pressure cuff 14. A 20 
second signal settlement period is used in a working embodiment. 
Subsequent to time t.sub.0, the system begins monitoring the waveforms P 
at t.sub.1, t.sub.2, t.sub.3, and particularly the system detects the foot 
of the wave at t.sub.1f, the peak of the wave at t.sub.1p, and the base of 
the wave at t.sub.1b. 
This detection of wave features is done by standard mathematical algorithms 
analyzing the waves during real time acquisition of data, that is, the 
pressure pulse waveform P. First, second and third derivatives of the 
acquired data signal may be utilized to locate waveform features. In the 
embodiment shown in FIG. 10, the system determines when three substantial 
identical pressure pulse waveforms P.sub.t have been received (based on 
peak height or integrated valve or otherwise) and then, after 
predetermined time period from detecting the initial slope of the third 
waveform at t.sub.3, the system generates a calibration pneumatic pulse 
V.sub.cc at time t.sub.4. The calibration volume V.sub.cc may be triggered 
by detecting and counting other waveform features. 
As described earlier in connection with the preferred embodiment, this 
volume change is achieved by cylinder head moving and expanding chamber 68 
a predetermined amount V.sub.cc See FIG. 2. This predetermined volume 
V.sub.cc is added to the pneumatic system and generates a measurable 
change in the pressure signal which is the calibration pressure pulse 
P.sub.cal. The system then computes the actual blood volume pulse V.sub.n 
in accordance with the following equation. 
EQU V.sub.n divided by P.sub.dia equals Vcc divided by P.sub.cal.Eq. 3 
The calibrated and measured blood volume pulse waveform V.sub.n is obtained 
by multiplying the measured or pre-set diastolic pressure P.sub.dia by the 
ratio of the V.sub.cc and p.sub.cal. The calibration volume V.sub.cc is 
currently 0.68 ml but may be set at 1 ml. Accordingly in display region 
212, the system displays the recorded pressure wave P.sub.n. 
Alternatively, the system may display the measured and corrected blood 
volume pulse waveform V.sub.n. In this situation, there is a time-based 
discontinuity in the display due to the signal processing of V.sub.n with 
P.sub.cal. Additionally, the system may illustrate the calibration pulse 
P.sub.cal. 
Subsequent to the calibration pulse at time t.sub.4, the pneumatic and 
electronic system may require a one or two wave period to settle in order 
to remove any transients caused by the calibration pulse V.sub.cc. The 
system ignores this second plurality of pressure waves at t.sub.5 and 
t.sub.6 in the calibration cycle. 
In FIG. 11, one embodiment of the present system is illustrated. In FIG. 
11, the calibration pulses are generated at times t.sub.4 and t.sub.11 
during a six cycle calibration period. In other words, the system acquires 
and records, in real time, pressure pulse waveforms P at times t.sub.1, 
t.sub.2 and t.sub.3, fires a calibration pulse V.sub.cc after waveform at 
t.sub.3 (calibration at time t.sub.4), enables the system to settle with 
waveforms P at times t.sub.5, t.sub.6 and time t.sub.7 (which 
post-calibration waveform data may be discarded), then acquires and 
records the next three pressure pulse waveforms P at times t.sub.8, 
t.sub.9 and t.sub.10 and subsequently fires a calibration volume V.sub.cc 
at time t.sub.11 into the system. Therefore, the calibration pulse is 
issued during a six pressure pulse waveform cycle, the system discards 
three subsequent post-calibration pressure pulse waveforms and saves and 
records the previous three pressure pulse waveforms immediately prior to 
the calibration pulse. Of course the system may record all pressure pulse 
waveform data but only utilize one, two or three pre-calibration waves to 
calculate data point V.sub.m in each calibration cycle per FIG. 8. The 
currently preferred embodiment records 12, five second strips of data 
during the long, ten minute RHT test. 
If the initial, critical data period for the reactive hyperemia episode 
lasts 5 minutes and if the patient's heart beats 60 beats per minute, 300 
pressure pulse waveforms are acquired, 20 are discarded during the quick 
release signal settlement period (20 seconds) about 140 pressure pulse 
waveforms are discarded in the post calibration cycles, and about 140 are 
available for processing as calibrated blood volume pulse waveforms data 
V.sub.n in the method and system. This data provides approximately 140 
potentially available data points V.sub.m and computation plot Q.sub.p 
versus episodic time shown in FIG. 8. 
FIGS. 12a-12b diagrammatically show the decreasing pulse height for the 
pressure pulse waveforms P.sub.t. The following Exemplary Timing Table 
describes FIGS. 12a-12b. 
______________________________________ 
Exemplary Timing Table 
______________________________________ 
t &lt; t.sub.o 
prior to t.sub.o, system is subject to transients due to the quick 
cuff 
release and is unstable and unsettled 
t.sub.o 
system is settled and wave counter started, record 
waveform function ON 
t.sub.1 to t.sub.3 
three (3) generally similar pressure waves P.sub.t identified 
t.sub.1F 
foot of waveform P.sub.1 at t.sub.1 
t.sub.1 
waveform marker and wave count N incremented 
t.sub.1P 
peak of waveform P.sub.1 
t.sub.1B 
base of waveform P.sub.1 
t.sub.2 
waveform P.sub.2 detected and wave count N incremented 
t.sub.3 
waveform P.sub.3 detected and counted 
t.sub.4 
system measureson volume change V.sub.cc 
pressure change P.sub.CAL due to calibration change 
- system computes blood volume waveform V.sub.n 
based on calibration -- displays V.sub.n or P.sub.n 
t.sub.5 -t.sub.6 
system settles and recovers from calibration event 
t.sub.8 -t.sub.10 
system confirms three (3) generally similar pressure waves 
P at t.sub.8, t.sub.9 and t.sub.10 
t.sub.11 
calibration event -- system computes the tenth blood volume 
data point V.sub.10 based on calibration event at t.sub.11 and 
- note this assumes system captured and 
calibrated V.sub.1, V.sub.2, V.sub.3, . . . V.sub.9 during 9 
P.sub.r waves where r is 
number of P waveforms per calibration cycle 
t.sub.15 -t.sub.17 
system confirms three good P waves 
t.sub.18 
calibration event - compute and display V.sub.12 based on 
calibration 
t.sub.18 and P at t.sub.17 
t.sub.22 -t.sub.24 
confirm similar waveforms 
t.sub.25 
calibrate and compute V.sub.32 with cal pulse t.sub.25 and P at 
- displayub.24 
______________________________________ 
The signal processing routines described herein may be changed. For 
example, to obtain an average blood volume pulse waveform V.sub.n -Ave, 
the embodiment locates a common waveform feature on each wave, e.g. the 
leading edge (first derivative and slope detection), and overlays 
multiple, predetermined waveforms atop each other. Another averaging 
technique includes computing the peak value V.sub.m, then averaging a 
predetermined number of peak values together to obtain V.sub.m -Ave. The 
averaging may be done on pressure waves P prior to calculating blood 
volume V. In the calibration routine, other calibration windows or cycles 
may be utilized. Herein, a six (6) waveform cycle is utilized. However, a 
four (4) or a ten (10) correction and calibration cycle may be 
appropriate. Further, rather than using a three (3) wave average, a six 
(6) wave average may be appropriate. 
With respect to the wave number and episodic time charts in FIGS. 8 and 9, 
if a six (6) wave calibration cycle is selected and a three (3) wave 
average is utilized (using waveform overlays as the averaging algorithm), 
the system counts the wave numbers N to track the calibration cycles and 
to compute V.sub.n -Ave as processed signal overlays. A correlation 
between episodic time and wave count is maintained by the processor and 
memory. Additionally, the computerized system starts a timer at the 
initial state T.sub.2 (FIG. 7) and keeps a running list or map of the wave 
number N and the episodic time (t.sub.1 t.sub.2 t.sub.3 t.sub.4 in FIG. 
8). After calibrating with six (6) wave cycles for five (5) minutes, 
correcting the pressure pulse waves P.sub.n and obtaining blood volume 
pulse waves V.sub.n, averaging to obtain V.sub.n -Ave, and calculating 
averaged peak values V.sub.m -Ave, the resulting 50 data points V.sub.m 
-Ave are then mapped to the corresponding reactive hyperemia episodic time 
with the stored time versus waveform number N. The system plots V.sub.m 
-Ave versus episodic time t as waveforms shown in FIGS. 8 and 9. The 
system also maps a data table with the averaged peak and episodic time. 
The episodic time may be at selected t.sub.1 f or t b or at calibration 
time t.sub.4 for each calibration cycle. See FIG. 10, waveform base, foot, 
peak or trailing base. Other episodic time markers may be selected. 
The display routines may also be modified from those described and 
illustrated above. For example, rather than display blood pressure pulse 
P.sub.n in display window 212 of FIG. 10, FIGS. 12a and 12b show the 
corrected and computed blood volume pulsatile waveform V.sub.n. If blood 
volume wave V.sub.n is illustrated, the displayed wave will have a time 
discontinuity between the inverted V-shaped wave V.sub.n and the measured 
calibration pressure pulse (a negative waveform) P.sub.cal. Basically 
V.sub.n is a computed value from P.sub.n as corrected by the ratio 
V.sub.cc versus P.sub.cal. 
Further, the system may sequentially show acquired and processed signals 
after the signal settle time frame (20 sec.) as follows: P.sub.n with 
P.sub.cal for 30 sec.; initial V.sub.n waves at episodic times 32 seconds, 
44 seconds, 56 seconds, 68 seconds, 80 seconds, 92 seconds (the first 
"clear data acquisition" time frame 60 sec. episodic period); secondary 
V.sub.n at about episodic times 122 seconds, 152 seconds (a V.sub.n data 
waveform in the second 60 sec. episodic clear time frame period); tertiary 
V.sub.n at about episodic times 182 seconds, 212 seconds, 302 seconds and 
332 seconds (V.sub.n data wave in the third 60 sec. episodic clear time 
period); the fourth and fifth V.sub.n representing fourth and fifth 
episodic periods; and blood flow Q.sub.p versus episodic time t (FIG. 8) 
for 60 sec. during or after reactive hyperemia test. Of course, blood flow 
Q.sub.p versus episodic time t is both a data table and a waveform plot of 
50 data points computed from V waves during real time acquisition period 
T.sub.2 and T.sub.3 and t.sub.4 (FIG. 7). 
Also, the computer system generates electronic and print versions of the 
reactive hyperemic test results as necessary. 
Blood volume and blood flow both characterize the condition of the 
patient's arterial system, the condition of the endothelium, the 
generation and transmission of NO and the action of drugs on those 
biological systems. Blood flow is a volumetric quantity of blood with 
respect to time. Typically, blood volume is measured in ml per minute. 
Blood flow is mathematically obtained from the V.sub.n waveform correlated 
to time. "Pulsatile" refers to the "pulse" caused by the heart pumping 
blood through the system. "Pulsatile" refers to the signal, flow or volume 
in excess of the basal value or rate. Waveform data is relatively easily 
converted into a data table once a constant time period has been selected. 
Similarly, data from a time based and mapped table can be reformatted as a 
wave or other time-based presentational display or print-out. "Mapping" 
involves the step or function of correlating data valves to a certain time 
frame and time period data. "Mapping" occurs both in a data table and a 
waveform illustration. 
In an initial working embodiment, the system operates as follows: 
Exemplary Process Table 
1. Gather and store patient data and risk profile data 
2. Obtain brachial BP when the patient is supine (e.g. 120/80) 
3. Inflate cuff to slightly less than diastolic pressure (80-5=75 mmHg) 
4. System calibrates, measures and stores base line P, V, V.sub.m and 
Q.sub.p 
5. Inflate cuff to suprastolic (120+20=140 mmHg) 
6. Occlude arterial system for five (5) minutes 
7. Quickly deflate to slightly less than diastolic pressure (80-5=75 mmHg) 
8. Let electronic and pneumatic system settle (about 20 seconds) 
9. Periodically calibrate, measure P.sub.n and V.sub.n and calculate 
V.sub.m and Q.sub.p data points (about 5 data point acquisitions and 
computations) for primary episodic data acquisition time (first 60 
seconds). Store data. Display as necessary. Correlate to episodic time. 
10. Repeat step 9 for remaining four (4) minutes of the short reactive 
hyperemic test (short RHT). Gather and calculate seven or eight additional 
data points V.sub.m and Q.sub.p (based on P.sub.n and V.sub.n) over the 
test period. 
11. Generate data table V.sub.m versus episodic time and Q.sub.p versus t. 
Print-out. Plot graph. Display. Print-out. 
12. Generate comparison data table with healthy RHT waves and data. Repeat 
with waveform. 
In a further enhancement, a carefully manufactured bellows with a 
predetermined volumetric size may be used rather that cylinder piston 
system 60. 
In a subsequent working embodiment (the currently preferred embodiment, 
subject to revision following a plurality of patent studies), the system 
operates as follows: 
Exemplary Process Table (Revised) 
1. Gather and store patient data and risk profile data. Display upon entry 
into system. 
2. Obtain brachial BP when the patient is supine (e.g. 120/80) by 
traditional methods. 
3. Start test. Inflate cuff to slightly less than diastolic pressure 
(80-5=75 mmHg). 
4. System calibrates, measures and stores base line P, V, V.sub.m and 
Q.sub.p Display. 
5. Inflate cuff to suprastolic (120+20=140 mmHg) via machine. 
6. Occlude arterial system for five (5) minutes. Display and possibly 
audibly announce a five minute countdown to cuff/pressure release. Provide 
early warning to patient immediately prior to cuff pressure release, "Do 
not move during RHT test." 
7. Quickly deflate cuff to slightly less than diastolic pressure (80-5=75 
mmHg). 
8. Let electronic and pneumatic system settle (about 20 seconds). 
9. Capture data. Periodically calibrate, measure P.sub.n and V.sub.n and 
calculate V.sub.m and Q.sub.p data points (average j number of signals to 
obtain e number of averaged signals during predefined time segment 
(quintiles) during 5 min. short test or 10 min. long RHT test. See Phase 
Process Table below for values of j and e) for primary episodic "clear 
data acquisition" time (subsequent to the 20 sec. signal settle time). 
Store data. Display as necessary. Correlate to episodic time. Display. 
10. Repeat step 9 for remaining test period (10 min. test) Gather and 
calculate data points V.sub.m and Q.sub.p (based on P.sub.n and V.sub.n) 
over the test period. Calculate Qp (ratio); Qp (phase); V.sub.m (ratio); 
V.sub.m (phase); and V (exp))explained below). 
11. Generate data table V.sub.m versus episodic time and Q.sub.p versus t. 
Print-out. Plot graph. Display. Print-out. 
12. Generate comparison data table with healthy RHT waveform or data. 
Repeat with waveform. 
One configuration of the user interface for present invention is 
diagrammatically illustrated in FIG. 13. This display shows the name of 
the patient, the name of the clinic or doctor conducting the test, and the 
current pressure reading from the pneumatic system in the upper horizontal 
region of the interface. Beneath this information bar is a data table (on 
the left-hand side) and a bar chart (on the right) showing the results of 
the test. During the test, portions of this data and bar chart are 
displayed such that the technician conducting the test obtains real-time 
feedback regarding the quality and quantity of data captured by the 
system. Beneath the RHT Test Data Table is a computational table, a 
display showing blood pressure data and the real time waveform display of 
pressure pulsatile signals (with a calibration pulse therein). 
______________________________________ 
RHT DATA TABLE (SHORT RHT TEST) (abbreviated) 
Time 
(min) Pcuff Pm Pcal Vm Qp 
______________________________________ 
Baseline 68 1.05 1.29 0.53 4.69 
0.3 79 1.75 1.39 0.82 9.06 
0.5 77 1.85 1.37 0.88 8.95 
0.7 78 1.90 1.38 0.90 8.71 
0.9 75 1.83 1.35 0.88 8.22 
1.1 76 1.91 1.36 0.91 8.59 
1.4 76 1.93 1.36 0.92 8.58 
1.7 76 1.84 1.36 0.88 8.56 
2.1 79 1.79 1.39 0.84 6.68 
2.6 74 1.66 1.34 0.80 7.97 
3.1 78 1.76 1.38 0.83 8.00 
3.6 73 1.24 1.33 0.60 6.32 
______________________________________ 
In addition to the tabular display of the RHT Data Table, the system, in a 
current embodiment, displays the following computations shown below in the 
Computational Display Table. 
Computational Display Table 
Qp Max Ratio=1.90 T (0-2 min) (1.sup.st quintile) 
Vm Max Ratio=1.70 T (4-6 min) (3.sup.rd quintile) 
V(Exp)=33.88 ml 
The computational display includes the variables set forth below. 
Variable Table 
Qp Max Ratio [a label]=x T (y min) (z quintile) 
where x=blood flow maximum value in ml per minute; 
where y=the time frame corresponding to max. blood flow Qp; and, 
where z=the quintile corresponding to max. blood flow Qp. 
Vm Max Ratio [a label]=r T (n min) (u quintile) 
where r=blood volume maximum value in cc; 
where n=the time frame corresponding to max. blood volume Vm; and, 
where u=the quintile corresponding to max. blood volume Vm. 
V(Exp) [a label]=k ml. 
where k=computational value of total blood volume measured during the 
entire RHT test (whether 5 min. (short test) or 10 min. (long test)). 
The RHT test may measure and monitor reactive hyperemia for the initial 
five (5) minutes of the hyperemic episode (typically capturing primary 
phase RHT data) or may measure and monitor reactive hyperemia for the full 
ten (10) minutes of the hyperemic episode. Researches do not have 
sufficient information at this time to determine the exact length of the 
RHT test. In any event, the operational aspects of the RHT test are 
substantially similar. Multiple and frequent calibrations are taken to 
gather and correct the raw blood pressure pulse data and compute blood 
volume pulsatile data and flow. The theories described herein are 
applicable to RHT tests ranging from at least three (3) minutes subsequent 
to the quick release of the suprasystolic cuff pressure to about ten (10) 
minutes post cuff pressure release. The claims appended hereto are meant 
to cover these test time frames. 
The following Phase Process Table refers to a long, ten (10) minute RHT 
test wherein the 10 minute data acquisition period is subdivided into 
fifths or quintiles. Other data acquisition segments may be established 
following clinical evaluations of a reasonable number of patients. The 
term "phase" refers to the time or episodic time of data acquisition. 
______________________________________ 
PHASE PROCESS TABLE (LONG RHT TEST) 
RHT Testing Phase 
Measurement 
Plotted Value (Qp and Vm) 
BL Time Baseline 
Baseline 
______________________________________ 
T (0-2 min) (1.sup.st quintile) 
0.5 min, 1 min 
Average (3 measurements) 
2 min 
T (2-4 min) (2.sup.nd quintile) 
3 min, 4 min 
Average (2 measurements) 
T (4-6 min) (3.sup.rd quintile) 
5 min, 6 min 
Average (2 measurements) 
T (6-8 min) (4.sup.th quintile) 
7 min, 8 min 
Average (2 measurements) 
T (8-10 min) (5.sup.th quintile) 
9 min, 10 min 
Average (2 measurements) 
______________________________________ 
The blood volume signals or the raw pressure pulse signals are averaged in 
this currently preferred embodiment of the invention. Averaging (a) 
reduces involuntary motion artifact corruption of the data (large movement 
by the patient requires electronic signal processing to detect and 
block-out or ignore the resulting signals which are aberrations of the 
true pressure pulse signals); and (b) smooths the signals. Data values may 
be averaged or waveform data may be averaged. In the currently preferred 
embodiment of the invention, wave peak data values are averaged. 
Mathematically, it does not matter whether pressure pulse data values or 
blood volume peak data values are averaged. Other averaging factors 
(rather than the 3 point and 2 point average) may be utilized. However, 
the time based accuracy of the pulsatile data deteriorates if higher 
averaging values are utilized by the data acquisition system. 
The Computational Display Table shown and described above is obtained from 
the following computations: 
##EQU1## 
The last formula for V (exp) refers to blood volume expansion or the 
capacitive value of the arterial system. During reactive hyperemia, the 
arterial system expands, captures a greater amount of blood volume than 
normally and temporarily stores that blood volume. This is similar to a 
capacitor which stores electrical energy for a time. In the arterial 
system, this stored, excess blood volume is dissipated over time from the 
peak or maximum value Vmax. The total blood volume generated, captured, 
stored and dissipated during the entire reactive hyperemic episode is 
indicative of the health and physiologic characteristic of the arterial 
system and the endothelium. At the present time, researchers do not know 
whether the phase of the signal (a time based analysis) or a total flow or 
volume or a combination of this data is most significant. 
The present working embodiment utilizes a ten minute test period after the 
five minute occlusion period. The episodic test period is divided into six 
(6) testing phases. To generate the aforementioned data, the electronic 
system electronically stores signals representing 12, five second strips 
of pressure waveforms. If necessary, the electronic system could store 
waveform signals for the entire 10 minute episodic test period. Simple 
data processing techniques are utilized herein due to the novelty of the 
test in the medical community. 
An important advantage of the present invention is the simplicity of 
operation. The technician asks the patient a series of simple questions 
(Do you smoke cigarettes? etc.), inputs the data into the system, takes 
the blood pressure of the patient by conventional methods, records this BP 
data into the system, wraps the cuff around the patient's arm, and presses 
a START key. The system thereafter operates in an automatic fashion. 
FIG. 13 also illustrates the baseline (BL) maximum blood volume Vm (ml), 
and the basal blood flow Qp (ml/min). In the current, revised working 
embodiment, the RHT test is divided into quintiles. Maximum blood volume 
Vm (averaged) and blood flow is shown in each quintile with a bar graph. 
An important data comparison feature is the difference between the 
baseline values and the values in each quintile. The display may be 
altered to show differences rather than actual values. Also, the bar graph 
may be replaced with a waveform display. The waveform may be generated by 
datapoints at the top of each bar in the bar graph plot. A waveform 
smoothing routine may be used to better illustrate the compiled data. 
The claims appended hereto are meant to cover modification and changes 
within the scope and spirit of the present invention.