Apparatus and method for recording monophasic action potentials from an in vivo heart

The apparatus comprises a probe having a tip portion, a first electrode mounted on a terminal free end of the tip portion and a second electrode spaced along the tip portion from the first electrode for supplying a reference potential. The probe is constructed so as to hold the first electrode in contact with tissue of an in vivo beating heart with a positive pressure without causing macroscopic damage to the heart tissue while orienting the probe such that the second electrode is spaced from the heart tissue. A stylet is retractably mounted within the probe, for allowing a physician to maneuver the probe through a vein or the like. Once the probe is in position, it may be replaced by a probe of a different shape. The probe may also be retracted while being inserted, for preventing internal injury to the patient. The stylet may have a noncircular cross-section for restricting directions in which it can bend. In an alternative embodiment, a combination catheter is disclosed, including pacing electrodes for pacing the heart while measuring the potentials thereof.

BACKGROUND OF THE INVENTION 
This invention relates to the recording of monophasic action potentials 
(MAPs) and more particularly to a method and apparatus for measuring MAPs 
by contacting heart tissue with a small electrode under positive pressure. 
Studies have been performed on tissues obtained from human hearts It has 
been learned that a resting cardiac cell has a transmembrane voltage 
difference of about 90 mV. The inside of the cell is negative relative to 
the extracellular fluid and, upon cell stimulation, an action potential 
ensues. The action potential consists of five phases. Phase 0 is rapid 
depolarization, phase 1 is an early repolarization, phase 2 is the plateau 
phase, phase 3 is a rapid repolarization to the diastolic transmembrane 
voltage, and phase 4 is the diastolic period. The time-voltage course of 
the action potential varies among different cardiac cell types. 
The electrical charge of the outer membrane of individual heart muscle 
cells is known as the membrane potential. During each heart beat, the 
membrane potential discharges (depolarizes) and then slowly recharges 
(repolarizes). The waveform of this periodic depolarization and 
repolarization is called the "transmembrane action potential." 
Mechanistically, the action potential is produced by a well-organized 
array of ionic currents across the cell membrane. 
The transmembrane action potential has typically been recorded by means of 
microelectrodes, which are extremely fine glass capillaries that can be 
impaled into a single heart muscle cell Because of the fragility of the 
glass capillary and the small dimensions of the heart cell, such 
recordings can be obtained only in small isolated tissue preparations, 
which are excised from animal hearts and are pinned down in a chamber with 
artificial solution It is impossible to use the microelectrode technique 
in the intact beating heart, such as in patients. 
Most of our knowledge about the electrophysiologic properties of the heart 
is based on the use of microelectrodes. However, because the 
microelectrode cannot be used in the human heart, there has been a lack of 
data relating to the elementary processes in the in vivo human heart, 
which may be different from the processes of the in vitro heart, 
particularly in disease. 
At the turn of the century, it had already been recognized that a potential 
similar in shape to the later-discovered transmembrane potential could be 
recorded if one electrode was brought into contact with an injured spot of 
the heart and the other electrode with an intact spot. Those signals 
became known as "injury potential" or "monophasic action potentials" 
(MAPs) because of the waveform shape. When it was found that the injury 
could be produced by suction, so-called suction electrodes were developed. 
Thus, to examine the time course of local electrical activity under 
experimental conditions in which microelectrode recordings are difficult 
or impossible to make, such as in the vigorous beating in-situ heart, 
investigators have often used suction electrodes. The signal obtained with 
suction electrodes is monophasic and, although of smaller amplitude, 
accurately reflects the onset of depolarization and the entire 
repolarization phase of transmembrane action potentials recorded from 
cells in the same vicinity. Suction electrodes have also been used in 
human subjects, but the potential for subendocardial damage and S-T 
segment elevation has limited its clinical use to short recording periods 
of two minutes or less. Because the shape and duration of the action 
potentials vary from site to site in the heart, longer recording time from 
a single endocardial site is needed to evaluate long-term MAP changes, 
such as heart rate effects over several basic cycle lengths or in response 
to pharmacologic interventions. These longer recording times have not been 
achievable, however, with suction electrodes, because of the resulting 
damage to the tissue. Primarily for this reason, the suction electrode 
technique has never gained wide clinical acceptance. Therefore, the gap 
between microelectrode studies in excised animal tissue and what is 
possible in the intact human heart has remained large. There still was no 
safe and reliable method to obtain such signals in the human heart itself, 
which could provide the most valuable information, without damage to the 
myocardium. 
Applicants herein have recognized that local heart muscle injury is not a 
prerequisite for the generation of MAPs, and that application of slight 
pressure with the tip against the inner wall of the heart would result in 
monophasic elevations of the signal if the filter settings were left wide 
open, i.e., from 0 to 5,000 Hz. Based on a theoretical evaluation of the 
signal modality and the factors that are responsible for its creation, 
applicants have found that these signals can be recorded reliably (i.e., 
without distortion) by using direct current (DC) coupled to amplification. 
In the past, no provision has been made for measuring the 
electrophysiological activity of a heart in the immediate vicinity in 
which the heart is activated by a pacing catheter Moreover, if it is 
desired to pace the heart at the same time as measuring MAPs in the heart, 
two entrance sites to the patient must be created and two catheters must 
be utilized, which is highly undesirable. 
Because of the complexity of electrical cardiac activity, when a pacing 
electrode is inserted into the heart, and it is desired to measure the 
resulting action potentials of the heart, it would be of extreme 
usefulness to be able to measure such potentials in the vicinity of the 
activation, rather than at a more remote location. 
Another problem to overcome is the slow DC drift caused by electrode 
polarization in conventional electrical material used in the recording of 
intracardiac electrical signals, such as silver or platinum. These 
materials are polarizable and cause offset and drift--which is not a 
problem in conventional intracardiac recordings, because those signals are 
AC coupled, which eliminates offset and drift. The MAPs, however, are to 
be recorded in DC fashion, and therefore are susceptible to electrode 
polarization. Applicants found that the use of a silver-silver chloride 
electrode material yields surprisingly good results in terms of both 
long-term stability of the signal and extremely low noise levels. 
Another important discovery herein has been that the tip electrode of the 
catheter should be held against the inner surface of the heart with slight 
and relatively constant pressure In order to accomplish this in a 
vigorously beating heart, a spring-steel stylet is inserted into a lumen 
of the catheter of the present invention to act as an elastic coil, 
keeping the tip electrode in stable contact pressure with the endocardium 
throughout the cardiac cycle. This leads to major improvements in signal 
stability. 
Thus, a main feature of the catheter of the present invention is to bring 
into close and steady contact with the inner surface of the myocardial 
wall a nonpolarizable electrode which both produces and records MAPs. To 
achieve this property, the electrodes are formed from nonpolarizable 
material such as silver-silver chloride, and the tip electrode should be 
maintained at a relatively constant pressure against the myocardial wall, 
preferably with some type of spring loading. The endocardial embodiment of 
the catheter of the present invention contains a spring-steel guide wire 
which provides this high degree of elasticity or resilience which allows 
the catheter tip to follow the myocardial wall throughout the heartbeat 
without losing its contacting force and without being dislodged. The inner 
surface of the heart is lined with crevices and ridges (called the 
trabeculae carneae) and are helpful in keeping the spring-loaded catheter 
tip in its desired location. The contact pressure exerted by the tip 
electrode against the endocardial wall is strong enough to produce the 
amount of local myocardial depolarization required to produce the MAP. The 
contact pressure is, on the other hand, soft and gentle enough to avoid 
damaging the endocardium or the myocardium or cause other complications. 
In particular, no cardiac arrhythmias are observed during the application 
of the catheter. Usually a single extra beat occurs during the initial 
contact the catheter tip against the wall, when it is observed. This is a 
result of the stable continuous contact of the tip electrode against the 
heart muscle, which is provided by the spring inside the catheter shaft. 
It is the tip electrode which is responsible for the generation and the 
recording of the MAP itself. A reference electrode, required to close the 
electrical circuit, is located approximately 3 to 5 mm from the tip 
electrode in the catheter shaft and is embedded in the wall so that it is 
flush with or slightly recessed in the catheter shaft, and makes contact 
only with the surrounding blood and not with the heart wall itself. 
This reference electrode is brought into close proximity with the tip 
electrode, since the heart as a whole is a forceful electrical potential 
generator and these potentials are present everywhere in the cardiac 
cavities. If the reference electrode were in a remote location, then the 
amplifier circuit would pick up the QRS complex. 
Another design feature important for the purpose of the MAP catheter is to 
ensure a relatively perpendicular position of the electrode tip with the 
endocardial wall. Again, the spring electrode is useful in this respect. 
Conventional catheters are usually brought into contact with the heart 
wall in a substantially tangential manner. Such conventional catheters are 
designed simply to record intercardiac electrograms, not MAPs. For the 
monophasic action potential catheter, direct contact of between the tip 
electrode and the endocardium is made. This also keeps the reference 
electrode, which is located along the catheter shaft, away from the heart 
muscle. 
To facilitate the maneuverability of the catheter during a procedure in the 
human heart, the distal end of the catheter should be relatively flexible 
during the time of insertion, and the spring-loading feature preferably 
comes into action only after a stable position of the catheter tip has 
been obtained. Thus, in a preferred embodiment the catheter is constructed 
in such a way that the spring wire situated in the lumen of the catheter 
is retractable. During catheter insertion, the spring wire or stylet is 
withdrawn from its distal position by approximately 5 cm, making the tip 
relatively soft. Once the catheter is positioned, the spring wire is again 
advanced all the way into the catheter in order to stiffen it and to give 
it the elastic properties that are important for the described properties. 
Important applications of the present invention are in the areas of 
directly studying the effects of drugs (for example, antiarrhythmia agents 
such as procainamide and quinidine) on the heart in real time; studying 
myocardial ischemia, and in particular, precisely locating areas of 
myocardial ischemia by studying localized MAPs; and diagnosing the nature 
and locality of arrhythmias originating from after-depolarizations. These 
after-depolarizations have hitherto been detected only in isolated animal 
tissue preparations where microelectrodes can be applied. The MAP catheter 
is a tool that can allow the clinical investigator to detect such abnormal 
potentials in the human heart and thereby significantly broaden our 
ability to diagnose this group of arrhythmias. 
SUMMARY OF THE INVENTION 
Therefore, it is an object of the present invention to provide an apparatus 
for measuring monophasic action potentials. 
A further object of the present invention is to provide a MAP measuring 
apparatus which can accurately record action potentials over sustained 
periods of time. 
Another object of the present invention is to provide a MAP measuring 
apparatus which can measure action potentials on a vigorously beating 
in-situ heart. 
Another object of the present invention is to provide a MAP measuring 
apparatus which, with slightly different modifications, may be employed to 
measure action potentials on both the endocardium and epicardium. 
Yet another object of the present invention is to provide a method of using 
the apparatus for recording MAPs. 
A further object of the present invention is to provide a method of 
detecting ischemia by sensing MAPs. 
In accordance with the above objects, the present invention includes an 
apparatus for measuring monophasic action potentials in an in vivo beating 
heart. The apparatus comprises a probe having a tip portion and a first 
electrode mounted on a terminal end of the tip portion such that a portion 
of the first electrode is exposed to ambient. A second electrode is spaced 
along the tip portion from the first electrode for supplying a reference 
potential signal. The probe is provided with structure for holding the 
first electrode in contact with tissue of the heart with a positive 
pressure without causing significant macroscopic damage to the heart 
tissue and for orienting the probe such that the second electrode is 
spaced from the heart tissue. 
In accordance with further aspects of the invention, a comparator is 
coupled to the first and second electrodes for subtracting signals 
received through the second electrode from the first electrode. The 
comparator is DC coupled to the electrodes and has a frequency response of 
approximately 100 kHz. 
The electrodes are non-polarizable, preferably formed of silver-silver 
chloride, to avoid direct current drift during the course of 
investigation. 
In accordance with further aspects of the invention, a flexible catheter 
may be used to hold the tip portion against heart tissue. The second 
electrode is exposed to ambient so as to contact fluid inside the heart 
The fluid acts as a volume conductor to establish continuity between the 
second electrode and tissue adjacent that contacted by the first 
electrode. A guide wire, which may be retractable, may be disposed in the 
catheter to aid in directing the tip portion. The guide wire in a 
preferred embodiment has a rectangular or other noncircular cross-section 
so that resistance to bending in at least one direction is higher than the 
resistance to bending in another direction, for assisting in the 
emplacement and positional stability of the catheter. 
In one embodiment, the first electrode is insulated from surrounding 
electrically conductive media such as blood by an insulating rim, relative 
to which the first electrode is recessed. 
The probe may also include means for establishing electrical continuity 
between the electrodes and between the second electrode and tissue 
adjacent the tissue contacted by the first electrode. The continuity 
establishing means may comprise saline solution absorbed in foam material. 
The saline soaked foam replaces blood as a volume conductor. 
The exposed surface of the first electrode may be approximately 1 mm across 
and the two electrodes are separated by a distance of approximately 3-5 
mm. 
The tip portion may also include an insulative material forming a raised 
ridge around the first electrode exposed portion, and the exposed portion 
of the first electrode may be generally planar. 
In one embodiment, the catheter of the invention is provided with a 
material at the distal end which is more flexible than the material of the 
main body of the catheter. In this embodiment, the stylet may be withdrawn 
at least partially from the distal end, so that the catheter may be 
inserted past obstructions (such as the tricuspid valve or branches in the 
femoral vein) without damage thereto, by allowing the distal end to flex 
back upon itself, avoiding vascular perforation or other injury. 
One embodiment of the invention includes an S-shaped distal end stiffener, 
which is advantageous in maintaining the desired force and substantially 
perpendicular position of the catheter against the endocardium. 
Another embodiment of the invention provides a combination pacing and MAP 
catheter for very localized study of the effects of pacing activity on the 
heart. 
In accordance with the invention, a method and apparatus are provided for 
determining the force with which the tip electrode of the catheter presses 
against the endocardium, wherein the catheter is fixed in position 
relative to a gram force gauge, and the distal end is placed into contact 
with a lever arm of the gauge, with the resulting force reading depending 
upon both the unstressed shape of the distal end and the stressed shape 
when the distal end contacts the lever arm. The force with which the 
electrode is actually applied to the in vivo heart strikes a balance 
between sufficient local depolarization of the myocardium for a good 
signal and avoiding damage to the heart tissue. 
The method according to the present invention comprises positioning the 
probe such that the first electrode is held against heart tissue with a 
positive force and such that the second electrode is spaced from the heart 
tissue. The method includes comparing signals from the first electrode to 
reference signals from the second electrode. 
According to one alternative to the method of the invention, the electrodes 
are short-circuited before contacting heart tissue by immersing the 
electrodes in a saline solution. 
When the probe includes a flexible catheter, the positioning step of the 
method includes percutaneous catheter insertion. 
The force applied to hold the first electrode in contact with heart tissue 
may be on the order of 20 to 50 g over the exposed area of the first 
electrode. A method and apparatus are provided herein whereby such force 
may be accurately determined, by placing the distal end of the catheter of 
the invention in a predetermined physical configuration against the lever 
arm of a force gauge.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
FIGS. 1 and 3 show a probe 10 according to the present invention. Probe 10 
comprises a tip portion 12 which is connected to an end of a relatively 
stiff, flexible wire 14. The end of wire 14 attached to tip 12 is 
L-shaped. Wire 14 is also bent into two loops to form a spring section 16 
and the opposite end of wire 14 attaches to a connector 18. A pair of 
electrical leads 20 and 22 are wrapped around wire 14. Leads 20 and 22 
extend from the tip portion 12 to connector 18 and attach to terminals in 
connector 18. Connector 18 is a conventional electrical connector for 
making contact with leads extending to amplification and display 
circuitry, to be discussed hereinafter. 
The portions of wire 14 above and below spring 16 are encased in plastic 
sheathing sections 24 and 26, respectively. Sheathing sections 24 and 26 
are shown in sectional view only in FIG. 1. 
Wire 14 can be conventional stainless spring steel wire which, combined 
with spring section 16, can produce a consistent force of approximately 20 
to 30 g at the tip portion 12 when the tip portion is held against a 
rapidly beating in vivo heart. Sheathing 26 can be Teflon tubing or the 
like, and connector 18 is a conventional electrical connector which 
receives leads 20 and 22. 
FIG. 2 shows tip portion 12 in greater detail. Wire 14 terminates part way 
into the tip portion. Sheathing 14 is filled with epoxy resin 30 beyond 
the termination of wire 14. The epoxy resin is firmly attached to wire 14 
and to the sheathing. A tip electrode 32 is embedded in the epoxy resin 30 
at the extreme terminus of the tip portion 12. Electrode 32 is a 
silver-silver chloride pellet which protrudes to form a smooth spherical 
surface approximately 1 mm in diameter. A proximal electrode 34 is also 
embedded in the epoxy resin 30 a distance of approximately 3-5 mm from the 
tip electrode 32 along tip portion 12. Proximal electrode 32 is also a 
silver-silver chloride pellet approximately 1 mm in diameter. Proximal 
electrode 32 is accessible through an opening 35 in sheathing 26. 
Electrodes 32 and 34 comprise a nonpolarizable matrix of silver-silver 
chloride. These electrodes are available in 1 mm pellets from In Vivo 
Metric Systems of California under the part no. E205. 
Electrical wires 20 and 22 are connected, respectively, to electrodes 32 
and 34 so as to provide electrical continuity between the electrodes and 
the terminals in connector 18. 
Sheathing 26 is covered with a layer of foam rubber 36 which extends from 
above electrode 34 to a level approximately equal to electrode 32. The 
foam rubber is substantially cylindrically shaped and soaked with a 0.9% 
saline solution. The primary purpose of the foam rubber is to suspend the 
saline solution so as to provide electrical conductivity between proximal 
electrode 34 and tissue adjacent that which is contacted by tip electrode 
32, as will be discussed hereinafter. 
Now, with reference to FIGS. 2 and 3, an example ;of the use of probe 10 
will be discussed. 
Mongrel dogs weighing 20 to 30 kg were anaesthetized by intravenous 
injection of sodium pentobarbital (25 mg/kg) or chloralose (60 mg/kg). 
Respiration was maintained with room air through a cuffed entotracheal 
tube by a Harvard respirator. The heart was exposed through left 
thoractomy and suspended in a pericardial cradle. 
Probe 10 was positioned against the epicardium 40 such that tip electrode 
32 contacted the epicardium with a force of approximately 20-30 g while 
the heart beat. The force was maintained by the spring steel wire 14 and 
spring 16 formed in wire 14. 
Epicardial MAP recordings were obtained by DC coupling the tip and proximal 
electrodes to a differential preamplifier 42, as shown in FIG. 9, with an 
input impedance of approximately 10.sup.11 ohms and a frequency range from 
direct current to 100 kHz. It should be noted that a preamplifier having a 
frequency range of direct current to approximately 5000 Hz should be 
sufficient for this application. The preamplified signal was displayed on 
a Tektronix storage oscilloscope 44 and written out on a multichannel 
photographic recorder 46. 
The probe 10, either mounted or hand held, provided continuous MAP 
recordings of stable amplitude, smooth contour, and isopotential diastolic 
baselines over prolonged time periods from a single epicardial site. FIG. 
10A shows an example of the epicardial MAP recordings. The arrow indicates 
the time at which contact pressure was applied. FIG. 10B shows the 
corresponding epicardial unipolar electrograms recorded by connecting the 
proximal electrode 34 of probe 10 to a second DC-coupled amplifier 42' 
(FIG. 9) and connecting a distant reference electrode 50 (FIG. 3) to the 
negative input of amplifier 42'. In FIGS. 10A and 10B, the first half of 
each graph was recorded at a speed of 10 mm/sec and the second half at a 
speed of 50 mm/sec. 
The distant reference electrode 50 was provided by another silver-silver 
chloride electrode sewn into the aortic root. The stability of the 
0-reference potential of the MAP recordings was checked at the beginning 
of each experiment and between interventions by comparing it with the 
diastolic potential recorded at the aortic root. 
The exact mechanism underlying the genesis of the contact electrode MAP is 
not clearly understood. It is theorized that the MAP recordings were 
obtained by exerting pressure with the tip electrode 32 against a small 
region of epicardium 40. This likely depolarizes a number of myocardial 
cells such that they are no longer capable of participating actively in 
regenerative depolarization and repolarization. The magnitude and 
direction of local current flow, which results from the potential 
difference between the depolarized cells under the tip electrode 32 and 
the adjacent normal cells would determine the amplitude and polarity of 
the extracellular MAP recording. The magnitude of current flow, however, 
may not only depend on the difference in membrane potential between cells 
subjacent and adjacent the electrode tip. Other factors, such as the 
number of cells depolarized and therefore involved in generating current 
flow, the degree of electrotonic coupling of cells at the boundary of 
interest, and the conductance in the extra- and intracellular media 
surrounding the recording sight are likely to influence extracellular 
current flow and the amplitude of the MAP. 
Referring again to FIG. 2, it should be understood that the purpose of the 
saline soaked foam rubber 36 is to provide a conductive path between 
proximal electrode 34 and the epicardium 40 surrounding tip electrode 32. 
In other words, the foam rubber acts as an extension of proximal electrode 
34 but does not pressurize the epicardium and thus does not cause 
depolarization of the myocardium. The actual potential being measured 
appears to be that between the depolarized myocardium directly beneath the 
tip electrode 32 and the surrounding tissue. 
FIG. 4 shows a catheter 60 used for bipolar measurements of MAps from 
endocardial sites. Catheter 60 has a tip portion 64 which is shown in 
greater detail in FIG. 5. Tip portion 64 contains a tip electrode 72 and a 
proximal electrode 74. Catheter 60 comprises flexible tubing 62 which may 
be Teflon or other durable material having a memory. Tubing 62 must be 
sufficiently flexible to be easily bent by the action of a beating heart, 
yet sufficiently resilient to maintain the tip portion 64 of the catheter 
in contact with the endocardium with a force estimated at approximately 
20-30 g. A stainless steel guide wire 66 is inserted in the tubing 62 to 
improve the resilience of the tubing and to aid in positioning the 
catheter tip portion 64. A pair of electrical leads 68 and 70 also extend 
through tubing 62 to make contact with tip electrode 72 and proximal 
electrode 74, respectively. The opposite ends of electrical leads 68 and 
70 are connected to electrical connectors 76 and 78, respectively. 
As shown in FIG. 5, tip 64 is similar to tip 12 of probe 10 except that no 
foam rubber is provided around the tip. Tip electrode 72, which is a 
sintered silver-silver chloride pellet of approximately 1 mm diameter, the 
same as tip electrode 32, protrudes from the terminal end of tip portion 
64. Electrode 72 is held in place by epoxy cement 80, or preferably by 
cyanoacrylate adhesive, which has been determined to be relatively inert 
and biocompatible. A silver wire 82 extends from tip electrode 72 and is 
soldered at point 84 to insulated lead 68. Similarly, proximal electrode 
74, which is spaced about 5 mm upwardly along the tip portion 64 from 
electrode 72, is fixed in position by epoxy 80 and is connected to a 
silver wire 86 which is soldered at point 88 to insulated lead 70. The 
proximal electrode 74 is accessible through an opening 90 in tube 62 and 
is recessed somewhat within the catheter so that contact is made only with 
the outer medium (blood) in the heart and not the endocardium. 
The tip and proximal electrodes of catheter 60 are connected to a 
preamplifier 42 (FIG. 9) through connectors 76 and 78 to provide 
oscilloscope and recorded readouts of the MAPs. A remote electrode can be 
placed in subcutaneous tissue remote from the heat, that is, at the site 
of catheter insertion, to provide intracavitary electrograms. 
Catheters have been employed having lengths from approximately 100-150 cm 
and a total outside diameter of approximately 1.3 cm. The spring steel 
guide wire may have a diameter of approximately 0.012-0.013 inches. 
An example of the use of catheter 60 will now be set forth. 
Before catheterization, electrodes 72 and 74 were immersed in sterile 0.9% 
saline solution for one hour with leads short-circuited to balance 
half-cell potentials. This procedure ensured that no appreciable direct 
current drift occurred during the course of the investigation. Diastolic 
baseline of intracavitary electrograms usually remain stable within % 1 mV 
during the entire recording time (1-3 hours). It should be noted that 
stainless steel or platinum electrodes conventionally used in clinical 
electrophysiology may produce considerable baseline drift of up to 160 mV 
during the first 30 minutes. After percutaneous catheter insertion by 
Seldinger technique and fluoroscopic positioning of the catheter within 
the heart, electrode leads were connected with sterile cables to the 
differential preamplifier 42. Firm approximation of the tip electrode to 
the endocardial surface was indicated by the recording of monophasic 
action potentials, which stabilized in amplitude and duration over a few 
beats. 
FIG. 6 depicts the catheter 60 measuring MAPs at several different 
ventricular sites in a heart. The various sites are numbered 1 through 6 
in FIG. 6. In each instance, positioning of the tip portion of the 
catheter was under fluoroscopic control. 
FIG. 7 and 8 show an alternate embodiment of a tip electrode 90 which can 
be used to replace either tip electrode 32 in probe 10 or tip electrode 72 
in catheter 60. Tip electrode 90 is again sintered silver-silver chloride 
with an exposed surface diameter of approximately 1 mm. However, the 
exposed surface 92 is substantially planar and is surrounded by a small 
ridge 94 of insulating material. This tip design has proven to be most 
effective in producing long-term stable recordings of monophasic action 
potentials. The ridge 94 aids in sealing off contact of electrode 90 from 
the adjacent tissue and fluid. The design o the reference electrode is as 
before, i.e. it is mounted along the shaft 3-5 mm proximal from the tip. 
The depth ridge 94 should only be approximately 0.1 mm. The purpose of 
ridge 94 is to seal off electrode 90 from the surrounding tissue but not 
to prevent the electrode from pressurizing the myocardium. electrode 90 
must both produce the pressure and sense the voltage in the pressurized 
tissue. If the height of ridge 94 is too great, electrode 90 will be 
prevented from producing adequate pressure. 
Ridge 94 creates a high resistance between the pressed tissue and the 
surrounding tissue. The thickness of ridge 94 should also not be too great 
so that the electrode is close to the boundary created by the ridge. 
Referring again to FIG. 1 and 4, it will be appreciated that the primary 
difference between probe 10 and catheter 60 is that probe 10 includes a 
saline soaked foam rubber piece 36. In probe 10, the saline solution acts 
as a volume conductor which establishes electrical continuity between the 
proximal electrode and the tissue surrounding the tissue pressed by tip 
electrode 32. With the catheter 60, the fluid (blood) within the heart 
itself is the volume conductor which serves this purpose. Therefore, no 
additional conductive material is required. 
It should also be appreciated that with prior known suction electrode 
catheters, focal hemorrhage results at the site of suction within a few 
minutes. In contrast, no macroscopic damage to the issue was seen in 
studies with the continuous contact electrode of the present invention. 
Furthermore, the stability of the contact electrode MAP over long 
recording periods may be considered indirect evidence that cellular 
alterations that lead to electrical uncoupling were minimal. 
Thus, MAP recordings using the present invention appear to be safe and can 
easily be performed during routine cardiac catheterization along with 
other electrophysiologic measurements and pharmacologic interventions. 
MAPs recorded with the present invention can also provide a sensitive 
index of acute myocardial ischemia. 
Identification of Ischemia/Infarction Using Monophasic Action Potentials 
The ability to localize a region of myocardial ischemia by epicardial MAP 
recordings has been examined in 8 dogs and compared with standard 
epicardial S-T segment mapping. In order to produce transmural ischemia 
and infarction in a canine heart, the left anterior descending coronary 
artery (LAD) was permanently ligated proximal to the first diagonal branch 
and a biologically inert, non-resorbable polymer (dental rubber) injected 
into the arterial lumen. The ligation is shown on FIG. 3 at 100. This 
technique of vascular embolization, which extends into the arterioles, has 
previously been shown to create transmural infarcts with sharp 
histological borders in canine hearts. The white color of the injectate 
was also helpful in determining the vascular distribution of the LAD. 
Prior to ligation, 6 to 8 control measurements of the epicardial MAP and 
unipolar electrograms were made from defined locations inside and outside 
the anticipated ischemic region. Epicardial mapping was begun one hour 
after LAD occlusion and embolization and was completed within 15 minutes. 
The hand-held recording probe 10 was consecutively placed at multiple 
sites within, outside and near the border of the area of visible cyanosis. 
In each dog, measurements were made from 45 to 645 sites with an increased 
frequency of recordings close to the visible cyanotic border (shown in 
FIG. 3). The distance of the recording sites to the visible border of 
cyanosis was measured with a flexible ruler and recorded spatially on as 
map of the epicardial surface. For graphic presentation of mean data, the 
amplitude and dV/dt max of the MAP and the total S-T segment voltage (T-Q 
depression plus "true" S-T elevation) were averaged in 2 mm intervals 
inside and outside the visible cyanotic border. These data are shown in 
FIG. 12, to be discussed hereinafter. 
In order to assess the effect of duration of ischemia on the 
electrocardiographic measurements, epicardial mapping was repeated in 2 
dogs, 3 hours after coronary artery ligation and embolization, at 
locations similar to the mapping study performed at one hour. The data 
obtained are shown in FIG. 13, also to be discussed hereinafter. 
In FIG. 10 are shown examples of MAP recordings (A) and standard unipolar 
electrograms (B) obtained from the epicardial surface of the canine left 
ventricle prior to ischemia. In general, MAP signals demonstrated "full" 
amplitude within 5 to 10 beats after stable contact of the electrode with 
the myocardial surface had been established. The time of contact as shown 
by the arrow in FIG. 10. Thereafter, MAP recordings remained stable in 
amplitude, dV/dt.sub.max and configuration for continuous recording 
periods of 1 hour or more. Using non-polarizable silver-silver chloride 
electrodes and DC amplification, it was possible to demonstrate a negative 
diastolic potential and a positive systolic potential with respect to the 
zero reference obtained from the diastolic baseline of the epicardial 
surface recording measured prior to application of significant contact 
pressure. Total amplitude of control MAPs recorded from the left 
ventricular epicardial surface ranged from 35 to 55 mV (42% 4 mV, means % 
S.D.) which is considerably smaller than amplitudes previously reported 
for transmembrane action potentials (120 mV). In addition, the ratio of 
the positive voltage ("overshoot") to the total amplitude was greater in 
MAP than in intracellular recordings. The total MAP duration measured at 
90% repolarization (MAPD.sub.30) was 144% 12 msec measured at a constant 
spontaneous heart rate of 120% 5/min. Similar durations have been reported 
for transmembrane action potentials of canine ventricular myocardium. 
To further examine the precision of MAP recordings for localizing regional 
myocardial ischemia, epicardial MAP recordings were made with the 
hand-held probe 10 across the border of the regions which was made 
transmurally ischemic by coronary artery ligation and distal embolization 
with dental rubber, as discussed above. FIG. 11 shows original MAP 
recordings (B), their first time derivative (dV/dt) (C) and adjacent, 
simultaneously recorded unipolar epicardial electrograms (A) at various 
distances from the cyanotic border one hour after induction of transmural 
ischemia/infarction. MAPs recorded 20 nm or more outside the visible 
border of cyanosis had amplitudes, durations, configurations and 
dV/dt.sub.max values comparable to those recorded at distant sites and 
comparable to those recorded at the same site prior to occlusion. 
Epicardial MAPs recorded from sites 10 mm or less outside the cyanotic 
border demonstrated noticeable decreases in plateau amplitude and duration 
and decreases in the slope of the final repolarization phase (phase 3), 
resulting in a more triangular shaped MAP with a greater total duration. 
Values of dV/dt.sub.max were also noted to be decreased at these sites. As 
the MAP recording probe was moved across the cyanotic border, MAP 
amplitude decreased sharply and dV/dt.sub.max values approached zero 2 mm 
inside the border. The decrease in MAP amplitude was due to a loss in both 
diastolic (negative) and systolic (positive) potential. In the center of 
the ischemic region, nearly isopotential recordings at negative potentials 
ranging from -15 to -5 mV were obtained. In contrast, epicardial S-T 
segment voltages were highest just inside the cyanotic border decreasing 
progressively toward the center of the ischemic region. As seen in FIG. 
11A, these increases in total S-T segment voltage were due to a 
combination of "true" S-T elevation and T-Q segment depression. The 
relative contribution of T-Q segment depression, however, was greater in 
recordings inside the ischemic region (where MAP recordings demonstrated 
markedly reduced diastolic potentials). In contrast, outside the cyanotic 
border, true S-T segment elevation contributed the largest portion of the 
total S-T segment change. 
In FIG. 12 are summarized MAP and total S-T segment recordings made in 8 
dogs across the lateral border of cyanosis 1 hour after induction of 
transmural ischemia. Unipolar epicardial electrograms demonstrating 
significant S-T segment elevations 27% 6 mV) were recorded 4 mm inside the 
cyanotic border. In epicardial electrograms recorded near the center of 
the ischemic region, both T-Q and S-T segment displacements were found to 
be lower in magnitude than those recorded just inside the border. Total 
S-T segment voltages in these more central ischemic regions (16-22 mV) 
were not significantly different in magnitude from those measured 4-6 mm 
outside the border (p. 13). Unipolar electrograms recorded in the center 
of the ischemic region did differ from those recorded. Just outside the 
border, however, by the presence of diminished R wave voltage and/or the 
presence of Q waves (FIG. 11). In particular, in FIG. 12, the uniform loss 
in MAP amplitude and dV/dt throughout the ischemic region should be noted. 
This is in contrast to the decline in S-T segment voltage towards the 
center of the ischemic region. 
The distribution of blood flow across the lateral border of the cyanotic 
region was determined in 6 dogs using the radioactive microsphere 
technique. Myocardial blood flow was 1.42% 0.35 ml/min/g in the 
subepicardial layers and 0.65 % 0.28 in the subendocardial layers 2-4 mm 
outside the visible edge of cyanosis and decreased to 0.01% 0.05 and 0.01% 
0.02 2-4 mm inside the cyanotic border. These flow data confirm that the 
technique used to produce transmural infarction in a canine heart resulted 
in a sharp lateral border of ischemia with a transition from normal to 
zero blood flow over a width of only 6 mm. 
The influence of the duration of ischemia on the transition of MAP and 
corresponding S-T segment recordings across the cyanotic border was 
studied in 3 additional dogs. These results are shown in FIG. 13. 
Measurements of MAP amplitude and dV/dt.sub.max repeated 2 hours after the 
initial mapping study demonstrated near zero values even closer to the 
edge of the cyanotic border than after 1 hour of ischemia as well as 
further reductions just outside the border. In contrast, epicardial S-T 
segment elevations demonstrated an overall decrease in magnitude over the 
same time period, making localization of the border even less well 
defined. 
The local epicardial S-T segment voltages recorded using probe 10 are 
consistent with previous reports of the ability of epicardial S-T segment 
mapping to delineate a region of ischemia. S-T segment elevations were 
found 20-mm or more outside the cyanotic border and reached maximum values 
just inside the border. As also demonstrated in previous studies, S-T 
segment voltages decreased towards the center of the ischemic area such 
that the magnitude of S-T segment elevations recorded in the central 
ischemic regions was not significantly different from those recorded at 
sites 5 to 10 mm outside the area of reduced flow. The wide zone of 
transition of epicardial S-T segment voltage across the border and the 
loss of S-T segment voltage in the center of the ischemic region are 
expected on theoretical grounds. S-T segment displacements are caused by 
current flow between normal and ischemic myocardium. Potential gradients 
and thus injury current flow are less between adjacent ischemic regions 
than between ischemic and normal regions resulting in greater S-T segment 
voltages closer to the ischemic border than in the center of the ischemic 
area. In contrast, loss of epicardial MAP amplitude and dV/dt.sub.max wire 
found to be uniform throughout the ischemic region, thus correlating 
better with the absence of flow. 
The transition from nearly absent to nearly normal MAP recordings across 
the cyanotic border occurred over a distance of less than 8 mm. This 
electrical transition was slightly greater in width than the flow 
transition which had a width of approximately 6 mm. The width of the 
border "zone" over which transition in flow, metabolism or 
electrophysiologic variables are detected depends on the resolving power 
of the techniques employed to measure these variables. The finding of 
intermediate values for flow, metabolites or electrophysiological changes 
could result from measurements obtained either from a mixture of normal 
and ischemic cells or from a uniform composition of cells with an 
intermediate degree of change. The slightly wider transition for MAP 
changes, as compared to the flow transition, may indicate a limit to the 
resolving power of MAP recordings or may reflect scatter related to 
microsphere flow measurements being made from 12 mm wide tissue samples. 
On the other hand, abnormal MAPs recorded just outside the cyanotic border 
do not necessarily indicate that the tissue recorded from is injured. 
Current flow between ischemic and nonischemic tissue may decrease the 
amplitude and rise velocity of transmembrane action potentials in 
nonischemic cells 
A decrease in the magnitude of S-T segment voltages with duration of 
ischemia (see FIG. 13) has been documented in both experimental and 
clinical studies. It has been reported that epicardial and intramural S-T 
segment potentials in the porcine heart reach maximal values 7 to 15 
minutes after coronary artery ligation and then decrease with time despite 
a progressive deterioration of the metabolic situation. Substantial 
reduction in S-T segment elevation in patients over the first 24 hours 
following acute myocardial infarction has been reported as part of the 
natural history of myocardial infarction. This discrepancy between S-T 
segment voltage and metabolic and histologic deterioration has been 
explained by progressive electrical uncoupling between damaged and normal 
myocardial cells so that, despite a persistent electrical gradient, flow 
of injury current decays and eventually ceases. In contrast 
ischemia-induced loss of MAP amplitude and dV/dt.sub.max persists or 
becomes even more pronounced three hours after coronary artery occlusion 
and distal embolization than after one hour. This indicates that the 
information on ischemic injury obtained from MAP recordings is not 
compromised by electrical uncouplinq as is the ECG, and suggest that MAP 
recordings can be used not only as a more precise but also more reliable 
electrophysiologic index for defining the spatial extent of 
ischemic/infarcted myocardium. 
In general, the apparatus and method of the present invention can be used 
to detect ionic imbalance due to a change in electrolyte balance in the 
heart as well as ischemia due to a reduction in blood flow. 
Monophasic action potentials MAPs) have hitherto mostly been recorded with 
suction electrodes. However, the "contact electrode" technique of the 
present invention provides more stable MAP recordings than suction 
electrodes and has been shown to also allow safe, long-term MAP recordings 
in human subjects without tissue injury. Endocardial and epicardial MAP 
recordings using the present invention have been found to resemble 
transmembrane action potentials and, following the induction of regional 
ischemia or changes in potassium ion concentration, undergo changes 
similar to those previously reported in intracellular recordings. 
Localization of a region of myocardial ischemia by MAP mapping is more 
accurate and less dependent on the duration of the ischemic process than 
S-T segment mapping. Endocardial MAP mapping in the cardiac 
catheterization laboratory and both epicardial and endocardial MAP mapping 
in the cardiac operating room should permit the identification of sites of 
regional ischemia in man and to assess the acute effect of therapeutic 
interventions designed to reduce the severity of an ischemic insult 
In FIGS. 14, 15 and 16 there is shown another embodiment of the apparatus 
of the present invention for measuring monophasic action potentials in an 
in vivo beating heart which also can be described as an intracardiac 
contact electrode catheter 101 which also can be identified as a probe. 
The catheter 101 consists of a flexible elongate element 102 which is 
provided with proximal and distal extremities 103 and 104. The flexible 
elongate element 102 consists of an outer jacket or body 106 and an inner 
jacket or body 107. The outer jacket 106 and the inner jacket 107 can be 
formed of a suitable material as, for example, they can be formed of heat 
shrinkable plastic such as polyethylene. The inner jacket 107 extends over 
a structural reinforcing tube 108 which can be in the form of 23 gauge 
hypodermic needle stock formed of a suitable material such as stainless 
steel. The tube 108 extends from the proximal extremity 103 of the 
catheter 101 into a region near the distal extremity 104 of the catheter 
101 as, for example, within eight centimeters of the distal extremity 104. 
Thus, by way of example for a catheter 101 of approximately 100 
centimeters in length, the tube 108 can have a length of approximately 92 
centimeters and would extend to an intermediate portion 109 as shown in 
FIG. 14 and 16. 
An additional stiffener element 111 extends from the distal extremity 104 
of the catheter as shown particularly in FIG. 15 and into the distal 
extremity of the tube 108. The stiffener element 111 can also be formed of 
a suitable material such as tempered stainless steel wire having a 
diameter of approximately 0.016 inches. It can extend from the distal 
extremity 104 as shown in FIG. 15 into a bore 112 provided in the tube 108 
and can extend substantially the entire length of the catheter. The 
tapering of the element 111 provides a graduation in the flexibility 
thereof such that the distal end of the element 111 is much more flexible 
than the proximal end. The tapered portion of the element 111 may be 
contained entirely within the S-shaped portion 156, so that the element 
111 is of substantially constant diameter between its proximal end and the 
portion 156. It should be appreciated that the additional stiffener 
element 111 can be eliminated where the additional stiffness is not 
necessary. 
A cylindrical electrode housing 121 is provided on the distal extremity of 
the inner jacket 107 and has its proximal extremity mated with the distal 
extremity of the inner jacket 107 and is secured thereto by suitable means 
such as an adhesive. To facilitate the making of a good bond between the 
housing 121 and the outer jacket 106, an annular recess 122 is provided in 
the distal extremity of the outer jacket 106 and an annular recess 123 is 
provided in the housing 121 which receive a sleeve 127 formed of a 
suitable material such as a polycarbonate and bonded therein by a suitable 
adhesive. 
An ovoid recess 128 is formed in the housing 121 and is approximately 0.064 
inches in length, and 0.046 inches in width. The distal extremity of the 
housing 121 is provided with an annular recess 29 which receives the 
proximal extremity of a cylindrical tip retainer 131 formed of a suitable 
material such as a polycarbonate and retained therein by suitable means 
such as an adhesive. A forwardly facing opening 132 is provided in the 
retainer 131. A conical type wedge 133 having a head 134 is seated in the 
bore 112 and expands the distal extremity of the inner jacket 107 so that 
it tightly engages the tip retainer 131 to provide a press fit. 
The retainer 131 preferably includes a rim 131a which defines the opening 
132 and protrudes slightly beyond the edge of the tip electrode 139. With 
this design, when the tip electrode is in place against an endocardial 
site, the rim 131a contacts the endocardium surrounding the site, and so 
prevents the tip electrode 139 from making electrical contact with blood 
within the heart. As can be seen the side electrode 141 is thus 
dimensioned so that it is slightly recessed within the recess 128 so that 
the outer periphery of the side electrode 141 is surrounded by the 
insulating material of the rim 131a which can provide a seal between the 
side electrode 141 and the blood. This ensures that the tip electrode is 
electrically isolated from the side electrode 141, which produces accurate 
and reliable MAP readings. 
A pair of electrical conductors 136 and 137 which can be formed of a 
suitable material such as insulated copper are provided which serve as 
signal wires. The conductors 136 and 137 are provided with S-shaped 
terminal portions 136a and 137a respectively which are embedded in a 
suitable conducting material to form electrical contact therewith to 
provide a tip electrode 139 and a side electrode 141. It has been found to 
be preferable to form the tip and side electrodes 139 and 141 by utilizing 
a silver-based conductive epoxy or other binder and adding to that 
approximately 20% by weight silver-silver chloride which has been found to 
provide a stable offset potential for a period in excess of one or two 
hours. 
A particularly suitable structure for the electrodes 139 and 141 is 
provided by utilizing silver-silver chloride flakes (rather than powder) 
bound together by cyanoacrylate adhesive. This will produce a particularly 
conductive electrode, and the cyanoacrylate is a relatively inert and 
strong binder which is biocompatible. 
It has been found such an electrode matrix has been particularly 
satisfactory in that it makes it relatively easy to manufacture the tip 
electrodes. After the tip electrodes are in place, they are machined to 
the desired conformation, for example, the convex shape for the side 
electrode 141. It is believed that this machining is also advantageous 
because in addition to shaping the electrode it exposes the silver-silver 
chloride crystals so that they come in direct contact with the heart 
during use of the apparatus or device as hereinafter described. The 
material can be molded and pressed around the S-shaped tips 136a and 137a 
of the conductors 136 and 137 thereafter permitting the conductive binder 
to harden in place. It has been found that it is desirable to place the 
side electrode 141 proximal of the tip electrode 139 by a suitable 
distance as, for example, 3 to 5 millimeters. 
The conductors 136 and 137 are connected at their proximal extremities to 
conductive flexible insulated leads 148 and 149 that terminate in adaptors 
151 and 152 respectively. A sleeve 153 formed of a suitable material such 
as a heat shrinkable plastic is mounted on the proximal extremity 103 of 
the catheter 101 and encapsulates the connections made (not shown) between 
the leads 148 and 149 and the conductors 136 and 137. 
As can be seen particularly in FIG. 14, a gentle S-shaped bend or curvature 
156 is provided in the proximal extremity of the catheter 101 which serves 
to provide the springiness desired to maintain the tip electrode 139 in 
contact with the heart muscle during the time that the heart is beating. 
As explained in connection with the previous embodiments, it is desirable 
that the catheter electrode housing 121 be disposed in a direction which 
is substantially perpendicular to the point at which the catheter engages 
the heart muscle which permits the tip electrode 139 to engage the surface 
of the heart and to leave the side electrode 141 free in the blood medium 
This ensures that there will be no short circuit between the electrodes 
except through the blood which serves as the conducting medium. The 
S-shaped curvature 156 is important in that it facilitates proper 
alignment of the distal extremity of the catheter 101 with the heart so 
that the perpendicularity hereinbefore described is obtained In addition, 
the S-shaped bend 156 provides a certain amount of resilience that ensures 
that a substantially constant contact pressure is provided against the 
endocardium while the heart beats. 
Thus, it can be seen that with the present invention a catheter has been 
provided which can be pressed against the heart with a force and position 
which remain substantially constant even while the heart is beating. The 
S-shaped bend is like an elastic spring to accommodate the movement of the 
beating heart while at the same time maintaining a substantially constant 
pressure on the heart so that accurate and precise signals can be obtained 
by the electrodes to make it possible to record stable signals over 
relatively long periods of time as, for example, one to two hours. 
FIG. 17 shows an alternative embodiment of the invention, depicting a 
catheter 200 which is a combination pacing catheter and MAP catheter. 
Thus, the new combination catheter 200 has been arrived at, in which 
pacing electrodes 210 and 220 are mounted at the distal end 230 of the 
catheter 200. In addition, a tip electrode 240 and a side electrode 250 
are provided, as in the configuration of FIG. 5, and are electrically 
connected to connections such as plugs 260 and 270, respectively. 
The pacing electrodes 210 and 220 are similarly connected to plugs 280 and 
290, respectively. Plugs 280 and 290 are standard plugs. The method of use 
of pacing electrodes such as electrodes 210 and 220 for activating is well 
known in the art in standard configurations pacing electrode catheters; 
that is, the same types of electrical signals which are provided to pacing 
electrodes in standard pacing catheters may also be provided to the 
electrodes 210 and 220 in the present invention. It will be understood 
that contained within FIG. 17 are the necessary electrical leads to the 
electrodes 210, 220, 240 and 250, and in addition stylets and other 
features as described herein with respect to other embodiments may be 
included. 
A coupling 300 for the plugs 260-290 is provided, insuring a reliable 
connection between the plugs to the electrical leads contained within the 
catheter 200. This coupling 300 is preferably of a hard material such as 
polycarbonate, and has an enlarged diameter relative to the catheter 200. 
This provides greater torque control for the user of the catheter when 
manipulating the catheter into the heart and positioning the tip electrode 
240 against the endocardium. 
In addition to the coupling 300, a knurled knob 310 may be attached at the 
proximal end 320 of the catheter 200. The knob 310 is preferably connected 
to the catheter 200 in a nonrotatable fashion, such that axial rotation of 
the knob 310 causes similar axial rotation of the catheter 200. As shown 
in FIG. 17, the knob 310 may be generally cylindrical in configuration, or 
may be of some other convenient shape for twisting by hand. 
An alternative embodiment for the distal end 230 of the catheter 200 is 
shown as distal end 235 in FIG. 17A. In this embodiment, two pacing 
electrodes (which are typically made from platinum) 215 and 225 are 
provided, with the pacing electrode 215 being disposed at the tip 245 of 
the distal end 235. In this embodiment, the tip electrode 255 is reduced 
in size (relative to the tip electrode 240), but the side electrode 255 is 
the same as in the configuration shown in FIG. 17. As with the FIG. 17 
embodiment, each of the electrodes 215, 225, 255, and 265 shown in FIG. 
17A includes its own electrical connection to a plug at the proximal end 
of the catheter. 
A distinct advantage of the configuration of FIG. 17A is that the pacing 
electrode 215 is positioned directly adjacent the tip electrode 255. As 
mentioned above, devices presently available are unable to provide pacing 
in the immediate vicinity of action potential measuring, and both the 
configurations of FIG. 17 and FIG. 17A for the first time provide such 
capability. In FIG. 17, the pacing electrodes 210 and 220 are preferably 
disposed as close to the tip electrode 240 as possible, with the 
configuration of FIG. 17A allowing the electrodes 215 and 255 to be 
extremely close, separated only by a layer of insulation 285, such as 
would separate two lumens in a catheter. Thus, pacing may be provided in 
the same area of myocardium as action potential measurement, providing a 
new and heretofore unavailable method of measuring the heart's reaction to 
pacemaking. 
One particularly useful advantage to the combination pacing/MAP catheter is 
in determining the effective refractory period of the heart, i.e. the 
longest interval between two separate stimuli to the heart where the 
second stimulus fails to energize the heart. In other words, the effective 
refractory period is the time required by the heart to recover from the 
effects of depolarization. There is a correlation between the effective 
refractory period (which may be on the order of 250 ms) and the action 
potential, and both of these may vary significantly from site to site 
within the heart. Thus, an important application of the combination 
catheter 200 is to detect the correlation between the effective refractory 
period and the MAPs generated for specific locations in the heart. Such an 
application is described in detail in the article by M. Franz (one of 
applicants herein) and A. Costard entitled "Frequency-dependent effects of 
quinidine on the relationship between action potential duration and 
refractoriness in the canine heart in situ," Circulation 77, No. 5, 
1177-1184, 1988, a copy of which is attached hereto as Appendix A, and 
which is incorporated herein by reference. It will be noted that the 
article of Appendix A describes such a method utilizing two electrodes; 
however, the embodiment of the current invention involving four electrodes 
(as in FIGS. 17 and 17A) also enables the use of such a method, and it is 
advantageous to use separate, slightly spaced, electrodes for the pacing 
electrodes and the MAP electrodes, respectively. 
Another alternative embodiment to the invention is shown in FIGS. 18-20. In 
this embodiment, a catheter 330 is provided of a configuration similar to 
that described with respect to the other embodiments herein, including a 
tip electrode 340 with its electrical connection 350, and a side electrode 
360 with its electrical connection 370. The catheter 330 is formed from 
two different materials, with a main section 380 formed from a relatively 
stiff material such as polyurethane, and a tip section 390 formed from a 
softer material, such as the PELLETHANE 2363-80A (trademark) polyurethane 
product produced by Dow Chemical. 
The tip portion 390 is preferably of a substantially solid cross-section, 
as shown in FIG. 19, with three lumens 400, 410 and 420 there through. As 
shown in FIG. 19, lumens 400 and 420 are generally circular in 
cross-section to accommodate the electrical connections or leads 350 and 
370. Other cross-sectional shapes for the lumen 400 and 420 are 
acceptable, so long as they accommodate the cross-sectional shapes of the 
connections 350 and 370. 
The lumen 410 is noncircular in cross-sections, and in the preferred 
embodiment is substantially rectangular. An elastic stiffener 430 is 
provided, and extends through the lumen 410 from the distal end of the tip 
section 390 to the main section 380. The elastic 430 may comprise a metal 
ribbon or other material which may be permanently bent into a desired 
configuration and have the characteristics of elasticity of springiness, 
so that when the distal end 440 of the catheter 320 is pressed upon 
slightly, the ribbon 430 will bend, but will spring back to its original 
shape upon release. However, more substantial pressure on the distal end 
440 i.e., bending the ribbon 430 such that the arc described between its 
first end 450 and its second end 460 changes substantially, will cause the 
ribbon 430 to deform into a different shape as desired by a physician or 
other user of the catheter 330. 
The main section 380 of the catheter 330 preferably includes a metal braid 
470 integrally formed or otherwise carried within the polyurethane 
material, as shown in FIGS. 18 and 20. The section 380 may be formed in a 
standard manner from two concentric tubes (not separately shown) of 
polyurethane, with the braid 470 placed into position in the outer tube, 
and the inner tube then extruded in position within the braid 470. 
The main section 380 is attached to the tip section 390 at a junction 480 
by means of an adhesive 490, shown in FIG. 20. The first end 450 of the 
elastic stiffener 430 preferably extends a short distance into the main 
section 380, and enough adhesive 490 is provided both to bind and seal the 
ends of the sections 380 and 390 where they abut one another at the 
junction 480 and to extend from the junction 480 to the first end 450 of 
the stiffener 430, providing a secure adhesion between the stiffener and 
the electrical connections 350 and 370, on the one hand, and the main 
section 380, on the other hand. The adhesive 490, which may be epoxy, 
cyanoacrylate-related adhesive, or some other appropriate adhesive, when 
hardened, also serves to stabilize the first end 450 of the stiffener 430, 
in effect anchoring it relative to the main section 380. 
In order to use the catheter 330, a physician first bends the tip end 390 
into the configuration he desires. It has been found that a generally 
C-shaped tip end is useful for maneuverability. The curvature of the arc 
between the first and second end 450 and 460 of the stiffener 430 may be 
greater or less, depending upon the size of the patient. The tip 390 
should be bent such that the stiffener 430 describes the resultant arc 
along its longer surfaces 500 and 510, rather than along its shorter 
surfaces 520 and 530. That is, from the point of view of FIG. 18, the 
surface 520 is parallel to the plane of the paper, whereas surfaces 500 
and 510 are perpendicular to the plane of the paper. The surfaces 520 and 
530 thus lie in parallel planes, whereas the broader surfaces 500 and 510 
described the arc between first and second 450 and 460 of the stiffener 
430. This is highly advantageous for torque control of the catheter 330 
when manipulating it into position. This is because the resistance to 
bending is much less if the bend is made along the surfaces 500 and 510 
(such as in FIG. 18) vis-a-vis the bend being made along the narrower 
surfaces 520 and 530. As with the other embodiment herein, the catheter 
330 is radiopaque, and a fluoroscope is used to position the distal end 
440 within the heart. With the configuration of FIGS. 18-20, it is very 
easy to predict how the tip section 390 will bend as it meets obstructions 
or vascular junctions while it is being positioned. This greatly increases 
the ease with which the physician may position the catheter 330, and in 
addition assists the physician in positioning the distal end 440 against 
the endocardium for MAP measurements. 
FIGS. 21-23 show another embodiment of the invention, comprising a catheter 
540, with, as in the other embodiments described herein, a tip electrode 
550 and a side electrode 560 electrically connected to plugs (not 
separately shown) at a proximal end of catheter 540. As with the 
embodiment shown in FIG. 5, the catheter 540 has a tip portion 570 and a 
guide wire or stylet 580, which is retractable. The catheter 540 also 
includes a main portion 590, which is made from a flexible material such 
as polyurethane. The tip portion 570 is also from a flexible material, but 
the materials for tip portions 570 and 590 are chosen such that the main 
portion 590 is considerably stiffer than the tip portion 570. The main 
portion 590 is connected to the tip portion 570 by means of a 
biocompatible adhesive 595. 
The catheter 540 is utilized as follows: the stylet 580, which is 
controlled from the proximal end of the catheter 540, is placed in its 
most distal position, as shown in FIG. 21. A curvature is chosen by the 
physician and provided to the distal end of the guide wire 580, much as 
with the stiffener 430 shown in FIG. 18. The catheter 540 is then 
maneuvered into the body, such as through the femoral vein. Observing the 
catheter through a fluoroscope, the physician may maneuver it up into the 
inferior vena cava, as shown in FIG. 22. When a vascular junction is 
reached, such as the junction between the hepatic vein and the inferior 
vena cava 600, as depicted in FIG. 22, the physician has the option of 
retracting the stylet 580, as shown in FIG. 22. The material of the tip 
portion 570 is flexible enough so that it will readily bend over into a 
bight without damaging or perforating the vascular tissue. Once past such 
an obstruction, the physician then has the option of replacing the stylet 
580 at its most distal position. 
FIG. 23 shows a very important use for this embodiment of the invention. 
Once the catheter 540 has reached the tricuspid valve 620 to the right 
ventrical 630, the stylet 580 is retracted out of the tip portion 570. 
Thus, the tip portion 570 is inserted into the right atrium 640, and may 
be pressed against the tricuspid valve 620 without damage thereto, since 
the tip portion 570 is soft and flexible. As the tricuspid valve opens, 
the tip portion 570 then springs back into position, such that its distal 
end enters the right ventricle 630. At that point, the catheter 540 may be 
pushed further into the right ventricle 630, and the tip electrode may 
then be positioned against the endocardium 650 for making MAP measurements 
from the endocardium 650 and the myocardium 660. At this point, the 
physician may withdraw the guide wire or stylet 580 entirely, and may 
insert a different guide wire, such as the stiffener element 111 depicted 
in FIG. 15, with its S-shaped distal end 156 (shown in FIG. 14 from 
outside the catheter). As discussed above, the S-shaped curvature is very 
useful in maintaining the tip of the catheter (such as at electrode 550, 
shown in FIG. 23) against the endocardium, and for providing the proper 
resilience or springiness to maintain contact with the endocardium as the 
heart beats. 
The force with which the tip of the catheter of the present invention 
presses against the endocardium is optimally within the range of 20-50 g 
of force. This force is arrived at by balancing two competing 
considerations. The first of these is that the tip electrode (such as tip 
electrode 340 of the catheter 330 shown in FIG. 18) should contact the 
endocardium sufficiently strongly that the myocardial cells in the 
vicinity of the tip electrode 340 are depolarized in a reliable fashion. 
Balanced against this is the consideration that the tip electrode 340 must 
not penetrate or damage the myocardium. 
A highly useful application for each of the embodiments discussed herein, 
such as the embodiments of FIGS. 14-23, is in the area of disease 
diagnosis, in particular in the measuring of drug effect (such as 
antiarrhythmia drugs) on the heart and in other diagnostic uses, such as 
measuring the reaction of the myocardium to varying types of signals 
provided to the pacing electrodes. Such applications are discussed in the 
article by E. Platia, M. Weisfeldt and M. Franz (applicant herein) 
entitled "Immediate Quantitation of Antiarrhythmic Drug Effect by 
Monophasic Action Potential Recording in Coronary Artery Disease," Am. J. 
Cardiology 1988; 61; 1284-1287, a copy of which is submitted herewith as 
Appendix B, and which is incorporated herein by reference. 
FIG. 24 shows an apparatus for standardizing the amount of force generated 
by the tip 340 pressing against the myocardium when the catheter 330 is in 
place. This apparatus and the method for using it are equally applicable 
to the other embodiments of the catheter of the present invention. 
A catheter force gauge 70 is shown, and includes a catheter receiving block 
680 mounted thereon, with the block 680 including a groove 690 for 
receiving the catheter 330. A clamp 700 is rotatably mounted on the block 
680 at axis 710, and may be tightened by means of a threaded knob 720 or 
other conventional means of clamping. 
A gram-force gauge 730 comprises the measuring portion of the 
catheter-force gauge 670, and is mounted in a fixed position relative to 
the block 680. The gauge 730 includes a measuring arm 740 and a dial 
indicator 750 of conventional design, wherein force against the arm 740 
causes a pointer 760 to indicate the amount of force on the dial indicator 
750. 
In order to utilize the catheter force gauge 670, the know 720 is loosened, 
and the clamp 700 is rotated out of the way of the groove 690. The 
catheter 330 is then laid in the groove such that the junction 480 between 
the main section 380 and the tip section 390 lies just at the upper left 
end 770 of the groove 690. Then the clamp 700 is rotated so that it 
overlies the catheter 330, and the knob 720 is tightened to hold the 
catheter 330 tightly within the groove 690. The tip electrode 340 is then 
placed in a cup-shaped receptacle 780 of the arm 740. It will be 
understood that the length of the arc a described between the tip 
electrode 340 and the junction 480 must be somewhat greater than the 
distance d between the arm 740 and the upper left end 770 of the groove 
690. In the preferred embodiment, arc a (i.e., the distance along the 
length of the catheter 330 between the tip electrode 340 and the junction 
480) is 4 inches, and the length d is 3 inches. 
Once the tip electrode is placed within the receptacle 780, the force 
reading will appear on the dial indicator 750. This force will depend upon 
the type of material utilized for the stiffener 430, as well as upon the 
configuration thereof, and the shape of the arc a into which the distal 
end of the catheter 330 is bent (i.e., the shape which it retains when not 
under tension). For instance, if the arc a is a fairly flat curve, such as 
a 30.degree. curve, then when the tip electrode 340 has been fitted into 
the receptacle 780, a reading of, for example, 22 g, may appear on the 
dial indicator 750, as shown in FIG. 4. However, if the distal end of the 
catheter 330 is bent into a tighter curve--such as a 40.degree. arc--then 
when the catheter 330 is placed in the gauge 670, a lower reading on the 
dial indicator 750 will result, since there is less tension required to be 
placed on the elastic stiffener 430 in order to place the tip electrode 
340 into the receptacle 780. In this manner, forces may be measured for a 
variety of stiffeners and radii of curvatures of the distal end of the 
catheter. Once a physician is acquainted with the approximate amount of 
curvature for a given configuration of catheter 330 which is necessary to 
generate the desired force, such as 22 g of force, he or she will be able 
to estimate the amount of force being exerted against the endocardium by 
the tip electrode 340 when the catheter 330 is inserted into an in vivo 
heart, by observing the distal end of the catheter 330 on the fluoroscope. 
The foregoing description is set forth for the purpose of illustrating the 
present invention. However, it should be apparent that numerous changes 
can be made in the invention without departing from the scope thereof, as 
set forth in the appended claims.