bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Cardiovascular Adjustments to Rapid Changes in Skin Temperature during Exercise
Authors: ROWELL LORING B. , MURRAY JOHN A. , BRENGELMANN GEORGE L. , KRANING KENNETH K.
Published: June 2012

In 11 normal men, central circulatory responses were measured while skin temperature was changed in a square-wave pattern during uninterrupted exercise (26% to 64% maximal oxygen consumption). Skin temperature was changed at 30-minute intervals, beginning at 32°C. On raising it to 38.2°C at low oxygen consumption (V
·
o
2
), cardiac output increased 2.5 liters/min, and central blood volume, aortic mean pressure, and stroke volume fell (7%, 7%, and 11%, respectively). Right atrial mean pressure fell 2.2 and 2.3 mm Hg during control and heating periods, respectively. All variables returned to control levels when skin temperature was reduced toward 26.9°C. Raising it to 40°C reproduced these changes with a more clear-cut drop in right atrial mean pressure. Results indicated reduced peripheral venous tone and cutaneous pooling of blood during heating and rapid reversal on cooling. On raising skin temperature to 38.7°C at high V
·
o
2
, cardiac output increased 19% (3.1 liters/min), stroke volume decreased 14%, and central blood volume rose slightly. Aortic mean pressure fell during the control period and was maintained or rose during heating periods. On cooling, central blood volume and stroke volume rose, cardiac output remained elevated, and aortic mean pressure fell. Increases in cardiac output during heating were related to skin temperature and not to V
·
o
2
or body temperature. At high V
·
o
2
, circulatory adjustments favor metabolic rather than thermoregulatory demands.
Hemodynamic Characteristics of Chronic Experimental Neurogenic Hypertension in Unanesthetized Dogs
Authors: FERRARIO CARLOS M. , MCCUBBIN JAMES W. , PAGE IRVINE H.
Published: June 2012

The hemodynamic changes accompanying experimental neurogenic hypertension due to sinoaortic denervation were measured in unanesthetized dogs for 3 weeks with chronically implanted arterial catheters and aortic flow transducers. Hypertension was modest, the average increase in mean arterial pressure being 31 ± 5 (SE) mm Hg. In about half of the dogs it was due predominantly to increase in cardiac output and in the others to increase in peripheral resistance; one factor or the other tended to maintain the hypertension in each dog throughout the experiments. Arterial pressure became extremely labile during the first few days after denervation and remained so during the entire experiment. This lability was closely correlated with environmental stimuli; rather minor distractions caused a sharp fall in pressure due variably to decrease in both cardiac output and peripheral resistance; greater distractions or physical activity caused a rise in pressure due usually to increase in peripheral resistance. Mean arterial pressures were higher when measured by transcutaneous puncture of a femoral artery, presumably because of the necessity of restraint and the discomfort associated with passage of a needle. Before sinoaortic denervation, arterial pressures fell to basal levels during sleep. After denervation, unexpectedly and for an undetermined cause, pressures rose to very high levels during sleep; the rises were consistently due to increase in peripheral resistance. Awakening was accompanied by a sharp fall in pressure and peripheral resistance.
Heart and Circulation of the African Lungfish
Authors: SZIDON JAN P. , LAHIRI SUKHAMAY , LEV MAURICE , FISHMAN ALFRED P.
Published: June 2012

Cardiovascular structure and function were studied in the African lungfish,
Protopterus aethiopicus
, by a combination of anatomical and physiological techniques. Particular emphasis was placed on mechanisms which operate under natural conditions in which air-breathing alternates with water-breathing. For such studies, awake, unrestrained fish were used after implanting devices for measuring blood pressure and flow. The results indicated that, despite ample anatomical opportunity for intracardiac mixing of the oxygenated and deoxygenated streams, in life the two streams were remarkably well separated. Also, using simultaneous pressure records from the consecutive cardiac chambers, the role of the pericardium in promoting venous return to the heart was clarified. On the basis of these observations, a hypothesis was formulated concerning the mechanisms by which the circulation is adjusted to the life habits of the lungfish, not only under its natural conditions as a water- and air-breather, but also during forced submersion and estivation.
Hypertension Caused by Salt Loading in the Dog
Authors: COLEMAN THOMAS G. , GUYTON ARTHUR C.
Published: June 2012

Experimental hypertension was produced in dogs by salt loading after renal mass had been surgically reduced to an estimated one-third normal. Salt loading was accomplished in one group of five dogs by administering isotonic saline in lieu of drinking water and in another group of six dogs by continuously infusing isotonic saline. Arterial pressure, cardiac output, heart rate, stroke volume, and total peripheral resistance were determined at frequent intervals during a 1-week control period and a 2-week salt-loading period in both groups. In addition, right atrial pressure, blood urea nitrogen, serum sodium, and serum potassium were determined in the group that was continuously infused. Both groups demonstrated an increase in mean arterial pressure to hypertensive levels, transiently increased cardiac output and stroke volume, initially depressed then subsequently increased total peripheral resistance, and initially depressed and variable heart rate. It is concluded that salt loading in a partially nephrectomized dog causes elevated arterial pressure that is initially induced by increased cardiac output but that is eventually sustained by increased peripheral resistance. Possible mechanisms are discussed.
Heart Mitochondrial Function in Acute and in Chronic Hyperthyroidism in Rats
Authors: PIATNEK-LEUNISSEN DOROTHY A. , LEUNISSEN REINHARD L.
Published: June 2012

The effects of acute versus chronic hyperthyroidism on rat heart mitochondria were explored. Acute, severe hyperthyroidism with an 18% loss of body weight was induced by injecting subcutaneously 10 µg/100g/day of triiodothyronine for 6 to 14 days, and chronic, anabolic, moderate hyperthyroidism was induced by placing triiodothyronine in the drinking water at a dose of 25 or 50 µg/100 ml for 15 to 60 days. Mitochondrial function was assessed polarographically using α-ketoglutarate as the oxidizing substrate, and mitochondrial structure was assessed indirectly from changes in rates of swelling in decimolar alkaline salt solutions in vitro. The P-O ratios of heart mitochondria isolated with Nagarse incubation from both types of hyperthyroid rats decreased slightly (15%) but significantly (
P
= 0.05). Simple dilution of the hyperthyroid mitochondrial suspensions effected a 75% increase in the P-O ratio of the acutely treated rats but only a 19% increase in that of the chronically treated rats. Significantly increased susceptibility to swelling in vitro was exhibited only by the mitochondria of the chronically triiodothyronine-treated rats. On the other hand, only those of the acutely treated rats showed significant increases in the activity of Mg
2+
-stimulated mitochondrial ATPase. These data suggest that the mechanisms whereby excess thyroid hormone in vivo affects the function and structure of isolated rat heart mitochondria vary with the mode of induction and the duration of the hyperthyroid state.
Input-Output Analysis for Total Input Rate and Total Traced Mass of Body Cholesterol in Man
Authors: PERL WILLIAM , SAMUEL PAUL
Published: June 2012

The Stewart-Hamilton theorems for flow and volume are generalized to yield total input rate and total traced mass in multiple input, steady-state systems with partially labeled input. Application is made to existing decay curves of tracer cholesterol in human serum measured under a control steady state and again under a steady state of neomycin administration which lowered the serum cholesterol level. The effect of neomycin on the total traced mass of body cholesterol was to reduce it by 38, 40, 32, and 24 g, corresponding to 34, 40, 25, and 33%, in four patients studied. The present analysis utilizes only the area and the first time moment of the plasma decay curve. It is applicable to decay curves of more general shape than those that can be fitted by a small number of exponentials. The analysis does not require the assumption of compartments.
Intrarenal Volumes of Distribution and Relative Diffusion Coefficients of Monohydric Alcohols
Authors: Chinard Francis P. , Thaw Colette N. , Delea Anne C. , Perl William
Published: June 2012

Indicator dilution outflow patterns in renal venous blood from anesthetized dog kidney were measured for the monohydric alcohols from methanol to hexanol with tritiated water (THO) and T-1824 dye as reference indicators. Also measured were olive-oil-to-water and red-cell-to-plasma partition coefficients. The indicator dilution results were: (1) at normal hematocrit, the mean transit times of all the alcohols were approximately the same as for THO; (2) at low hematocrit, the mean transit time of hexanol was approximately 1.6 times that of THO; (3) at both normal and low hematocrits, the upslope portion of the alcohol curves was earlier and steeper dian that of the THO curve, the more so with increasing alcohol carbon number. Results 1 and 2 and the partition coefficients were consistent with an increased volume of distribution of hexanol relative to THO, due to the lipid content of kidney cortical tissue. The previously reported convection-diffusion model applied to result 3 provided diffusion coefficients of the alcohols relative to THO in kidney cortical tissue in vivo.
Bradykinin Production Associated with Oxygenation of the Fetal Lamb
Authors: HEYMANN MICHAEL A. , RUDOLPH ABRAHAM M. , NIES ALAN S. , MELMON KENNETH L.
Published: June 2012

Previous studies showed that synthetic bradykinin produced in-vitro constriction of the ductus arteriosus of the fetal lamb and guinea pig, constriction of isolated human and lamb umbilical vessels, and pulmonary vasodilatation in the fetal lamb.

The present study showed that bradykinin precursor, kininogen, is present in arterial blood of the fetal lamb by 61 days of gestation and that its concentration increases toward term. We studied the bradykinin-generating system in 6 exteriorized fetal lambs. Kininogen concentrations in left atrial blood decreased within 1 to 2 minutes after beginning ventilation with O
2
, and free bradykinin was detected in left atrial blood. Pulmonary arterial blood kininogen concentration was not significantly altered. Kininogen concentration in left atrial blood did not fall in 4 other lambs ventilated with N
2
but did fall after subsequent ventilation with O
2
. To study the effects of increased oxygenation in utero without lung expansion, 6 pregnant ewes were exposed to hyperbaric O
2
at 3.63 atmospheres absolute. Associated with a mean increase in brachial arterial blood Po
2
to 44 mm Hg, a value equivalent to that in the ventilated exteriorized fetus, kininogen concentration fell, and free bradykinin was detected in the brachial arterial blood of 3 of the 6 fetuses. In 4 other exteriorized lambs we measured kininogen concentration in brachial arterial and right ventricular blood at frequent intervals up to 30 minutes after ventilation with O
2
. The concentration in brachial arterial blood fell before that in right ventricular blood.

The hypothesis is presented diat bradykinin is produced from kininogen in the lungs of the fetal lamb when oxygenated, and that the maximal rate of production occurs during the first few minutes after expansion of the lungs or exposure of the ewe and fetus to hyperbaric O
2
.
Total and Regional Coronary Blood Flow Measured by Radioactive Microspheres in Conscious and Anesthetized Dogs
Authors: DOMENECH RAUL J. , HOFFMAN JULIEN I. , NOBLE MARK I. , SAUNDERS KENNETH B. , HENSON JAMES R. , SUBIJANTO SUJANTO
Published: June 2012

Total and regional coronary blood flow were measured in dogs by left atrial injection of carbonized microspheres labeled with different radioactive isotopes (mean diameter 14 to 61µ). Simultaneously blood was collected at 20 ml/min from a catheter tied into a peripheral artery. The ratios of flow to radioactivity in myocardium and arterial blood should be equal if microspheres are well mixed in the aortic root and are distributed regionally in proportion to flow. This was proved in seven right heart by-pass experiments where coronary venous drainage was measured directly. Also, less than 0.1% of total myocardial radioactivity appeared in coronary venous blood, even with hypoxemia and small microspheres.

Total coronary flow in seven conscious dogs averaged 95 to 150 ml/min/100 g heart; and flow to the left ventricle was 111 to 169 ml/100 g. Although not validated independently, there was evidence that values for flow to each ventricle, the atria and the septum were correct.

The radioactivity per gram of left ventricular subendocardial muscle was 2.5 times that of subepicardial muscle using microspheres 51 to 61µ in diameter, but the ratios were 1.4 and 1.3 using microspheres of mean diameters 20 to 23µ and 14µ, respectively. It is unlikely that any of these microspheres measure blood flow to small portions of the ventricle.
Comparison of Abdominal and Thoracic Aortic Medial Structure in Mammals
Authors: Wolinsky Harvey , Glagov Seymour
Published: June 2012

Previous studies of adult mammalian thoracic aortas revealed that tension per medial lamellar unit was independent of species and that distribution of medial vasa vasorum, number of medial lamellar units and medial thickness were consistently related. Except for man, a similar pattern prevailed in abdominal aortic segments of all of the ten species studied. The human abdominal aortic media had relatively fewer lamellar units for its diameter than abdominal or thoracic aortas of other species, resulting in a relatively elevated estimated mean tension per lamellar unit. Vasa were normally absent from the human abdominal aortic media, even though its thickness significantly exceeded the thickness of avascular medias of other species and of avascular zones of medias with vasa vasorum. Elevated calculated tension per lamellar unit and excessive avascular thickness may be factors in the increased susceptibility of human abdominal aortas to atherosclerosis.
Effect of Nicotinate Ester, Acetylcholine, and Other Vasodilating Agents on Cutaneous and Mesenteric Vascular Smooth Muscle
Authors: Winkelmann R. K. , Sams W. Mitchell , Bohr David F.
Published: June 2012

Vasodilating agents were tested on smooth-muscle strips of small arterial blood vessels of dog and rabbit skin and mesentery, and two patterns of reaction were demonstrated. The type 1 Vasodilating agents, for example nicotinate, caused relaxation of contracted strips or blocked their contraction. The type 2 Vasodilating compounds, histamine, choline esters, and bradykinin, either caused contraction or had no effect on the vascular smooth-muscle preparation. Responses that were species specific and region specific characterize the action of type 2 vasodilators and must be accounted for in any in-vitro testing procedure for vasodilator drugs.
Maximum Velocity as an Index of Contractility in Cardiac Muscle
Authors: POLLACK GERALD H.
Published: June 2012

The use of maximum velocity of shortening (V
max
) as an index of contractility has been based on the assumption that V
max
of muscle fibers is equivalent to V
max
of the contractile element. It is shown here that such equivalence applies to the two-element model of skeletal muscle but not to three-element models of cardiac muscle. Analysis of published data in terms of the Voigt and Maxwell three-element models shows that the V
max
of the contractile element, unlike that of the muscle fibers, is not independent of fiber length but increases at least 50% for a 25% increase of fiber length. Moreover, V
max
of the contractile element is seen to be even more highly dependent on fiber length when correction is made for the nonuniform contribution of levels of active state to the force-velocity curves giving rise to V
max
of the contractile element.

It appears that in cardiac muscle an inotropic shift of V
max
of the contractile element cannot be distinguished from a shift due to change in fiber length, thus invalidating it as an index of contractility.
Relationship of Plasma Peptides to the Myocardial Depressant Factor in Hemorrhagic Shock in Cats
Authors: LEFER ALLAN M. , MARTIN JULIAN
Published: June 2012

The pathophysiological relationships of a myocardial depressant factor (MDF) present in the plasma of cats in hemorrhagic shock were studied. Aprotinin (Trasylol), an inhibitor of a variety of proteases including kallikrein and trypsin, prolonged survival of cats in postoligemic shock as well as prevented the appearance of MDF in the plasma. Trasylol did not alter the arterial blood pressure, venous pressure, or heart rate of these cats in shock, nor did it protect by exerting a positive inotropic effect. Trasylol was ineffective in preventing or reversing the negative inotropic effects of MDF in isolated cat papillary muscles. Column chromatography of plasma from control cats, from untreated shocked cats and from cats treated with Trasylol before shock showed six peptide peaks, designated A, B, C, D, E, and F in decreasing order of molecular weights. Peptides corresponding to peaks A, B, E, and F exhibited insignificant myocardial depressant activity. The peptide corresponding to peak C was present in control plasma and accounted for some of the small negative inotropic effect of control plasma. The peptide corresponding to peak D had a marked myocardial depressant effect which could account for all the activity of shock plasma. The molecular weight of this peptide was estimated to be 800 to 1000. This peptide is not bradykinin, but appears to be produced by a protease present in shock.
Inhibition of Reflex Vasoconstriction after Experimental Coronary Embolization in the Dog
Authors: TOUBES DANIEL B. , BRODY MICHAEL J.
Published: June 2012

The possibility that failure of vascular resistance to increase contributes to hypotension after myocardial infarction was examined in the hindlimbs of dogs following embolization of the coronary arteries. Vascular resistance did not change significantly during sustained severe hypotension after embolization in either the intact hindlimb or in simultaneously autoperfused innervated and denervated hindlimbs using constant flow. In nonembolized animals, an immediate large increase in hindlimb vascular resistance occurred when equivalent hypotension was produced by stimulation of the distal end of the sectioned vagus nerve. Lack of such response during hypotension after embolization suggested that inhibition of reflex vasoconstriction had occcurred. Bilateral cervical vagotomy allowed normal reflex vasoconstriction to proceed during hypotension after infarction. These data indicate that (1) since vascular resistance is unchanged in both innervated and denervated hindlimbs, normal neurogenic vascular tone is sustained during hypotension after myocardial infarction and (2) the baroreceptor reflex, which normally promotes vasoconstriction during hypotension, is inhibited reflexly following myocardial infarction, probably by activation of cardiac vagal afferents.
Changes in Content of Purine Nucleoside in Canine Myocardium during Coronary Occlusion
Authors: OLSSON R. A.
Published: June 2012

The use of a sensitive double-beam spectrophotometer and modifications in enzymatic assay techniques permitted the measurement of adenine nucleosides in extracts of canine left ventricle. In hearts not subjected to left coronary occlusion, adenosine content averaged 0.32 ± 0.04 (
SE
) nmole/g, increasing to an average of 1.82 ± 0.21 (
SE
) nmole/g after 15 seconds of coronary occlusion. The myocardial content of inosine plus hypoxanthine was 1.07 ± 0.21 (
SE
) nmole/g without coronary occlusion, rising to 1.98 ± 0.24 (
SE
) nmole/g after 15 seconds of coronary occlusion. Unlike the myocardial content of adenosine and inosine, the myocardial content of hypoxanthine did not appear to change during coronary occlusion.
Response of the Rat Aortic Media to Hypertension
Authors: WOLINSKY HARVEY
Published: June 2012

Clinical and experimental studies indicate that hypertension accelerates the development of arteriosclerosis. Morphological and chemical studies of the distended rat thoracic aorta were undertaken to define the structural and compositional alterations of the media which accompany hypertension and to relate these changes to increases in calculated medial stress. An 8-week period of hypertension was associated with significantly greater diameter, medial thickness, and cross-sectional area of the media of the thoracic aorta than in normotensive animals. Calculated wall tension was significantly higher in hypertensive animals, but the number of medial lamellar units was not greater than that usual in normotensive animals; this resulted in a strikingly elevated value for calculated tension per medial lamellar unit for the aortas of hypertensive animals. A highly significant linear relation was found between total tension and cross-sectional area of the media of the same segment. In addition, the absolute amounts of both medial elastin and collagen were increased in hypertensive animals; however, the percent of these elements remained essentially constant, indicating little change in the composition of aortic tissue. Increments in both fibrous proteins were linearly related to increases in calculated mural stress, and medial accumulations of elastin and collagen proceeded at similar rates. These findings demonstrate a linear relation among vessel dimensions and amounts of medial elastin and collagen and calculated wall tension.
Influence of Extracellular K
+
Concentration on Cable Properties and Excitability of Sheep Cardiac Purkinje Fibers
Authors: DOMINGUEZ GRACIELA , FOZZARD HARRY A.
Published: June 2012

Conduction velocity was increased from 3.5 m/sec to 4.1 m/sec in sheep cardiac Purkinje fibers when the superfusing Tyrode solution was changed from 2.7 mM K
+
to 4.0 mM K
+
. Further increase to 7.0 mM K
+
resulted in a fall in conduction velocity to 3.3 m/sec. To understand the nature of the cellular change responsible for this effect, cable analyses were made. With increases in extracellular K
+
concentration membrane resistance decreased and membrane capacitance did not change. Resistance of the myoplasm tended to fall in 7.0 mM [K]
o
. Since these effects did not explain the change in conduction velocity, excitability was studied by strength-duration curves using intracellular micropipettes for current passage and recording. Increase in K
+
from 2.7 to 4.0 mM resulted in a shift of the entire curve to the left, with a fall in rheobasic current from 121 to 104 nanoamperes and a fall in the time constant from 2.79 to 2.4 msec. Normalized plotting of stimulating current over rheobasic current (I/I
Rh
) against duration of stimulating current over the time constant (t/τ) suggested that the curves were not basically different. The increase in K
+
from 2.7 to 4.0 mM was associated with a depolarization of the resting membrane, consistent with alteration in the potassium equilibrium potential, but no change in the absolute membrane potential for threshold. In this way, the changes in membrane voltage and charge necessary for excitation were reduced in 4.0 mM [K]
o
.
Regression of Coronary Atheromatosis in Rhesus Monkeys
Authors: ARMSTRONG MARK L. , WARNER EMORY D. , CONNOR WILLIAM E.
Published: June 2012

Rhesus monkeys subjected to the atherogenic stimulus of a high-fat, high-cholesterol diet showed significant coronary atheromatosis at the end of 17 months. Smaller fibrotic lesions with scant stainable lipid were found in animals that were subsequently fed either of two cholesterol-free diets for 40 months. The average cross-sectional area of the lumen was more than 80% greater in regression animals than in monkeys with baseline atherosclerosis. The data support the hypothesis that uncomplicated coronary atheromas may regress in primates in appropriate dietary settings.
Intracellular Calcium and Myocardial Contractility
Authors: SUKO JOSEF , UEBA YASUYUKI , CHIDSEY CHARLES A.
Published: June 2012

Postextrasystolic potentiation was studied in the isolated perfused rabbit heart to determine its effect on intracellular calcium, sodium, and potassium concentration,
45
Ca uptake, and calcium distribution in mitochondria and microsomes. Paired stimulation at 80/min augmented myocardial contractility with a gradually developing increase in total intracellular calcium and sodium. A greater
45
Ca uptake was also observed and this was proportionate to the increase of intracellular calcium so that no change in exchangeable calcium occurred. A small but statistically insignificant increment was observed in mitochondrial and microsomal calcium. An increase of the rate of single stimuli to 160/min produced a minimal change in myocardial contractility compared to paired stimulation at 80/min, no change in total intracellular calcium, and a greater calcium uptake so that there was a significant increment in exchangeable calcium. Although these experiments do not identify the cellular processes responsible for the positive inotropic response to paired stimulation, they suggest that an alteration of myocardial calcium metabolism is involved. Furthermore, it is apparent that this alteration is distinct from that occurring during a comparable increase in the rate of delivery of single stimuli to the heart.
Pressure-Dependent Heterogeneity of Renal Cortical Blood Flow in Dogs
Authors: MCNAY JOHN L. , ABE YOUICHI
Published: June 2012

We determined the effect of perfusion pressure on the distribution of blood flow within the renal cortex of the anesthetized dog. Total blood flow to the denervated kidney was measured by an electromagnetic flowmeter and perfusion pressure was manipulated over the autoregulatory range (136 to 81 mm Hg) by an aortic clamp. Distribution of cortical blood flow was determined by the radioactive microsphere technique. Tissue perfusion rates of four cortical zones of equal thickness differed significantly from each other at normal arterial pressure. In sequence from superficial to deep, perfusion of the cortex zones averaged 4.18, 6.80, 3.07, and 1.68 ml . g
-1
. min
-1
. Aortic constriction significantly reduced perfusion of the outer cortical zone and augmented perfusion of the inner two cortex zones. Twelve percent of total renal blood flow was redistributed by pressure reduction. Atropine, 1 mg/kg, had no effect on cortical perfusion rates at either pressure. The influence of microsphere diameter and density on cortex perfusion rates was systematically studied and found to be minor. This observation implies that the microsphere method is valid for measuring distribution of blood flow within the renal cortex. We conclude that zones of the renal cortex are perfused at different rates and respond differently to changes in arterial pressure.
Increased Cardiac Output as a Contributory Factor in Experimental Renal Hypertension in Dogs
Authors: FERRARIO CARLOS M. , PAGE IRVINE H. , McCUBBIN JAMES W.
Published: June 2012

It has been suggested, but not established, that renal hypertension is initiated by increase incardiac output. Recent refinements in electromagnetic flowmeter technology allowed a critical reevaluation of this possibility. Flowmeters were implanted around dogs' ascending aortas and arterial catheters inserted; measurements were made daily before and after production of hypertension by the cellophane perinephritis method. Eight to 15 days after wrapping one kidney in cellophane, with the opposite kidney untouched, group averages for both stroke volume and cardiac output rose significantly (P < 0.005) though there was no change in arterial pressure. Both heart rate and peripheral resistance decreased slightly. Following these measurements, the contralateral normal kidney was removed and measurements were recommenced 24 hours later. After 4 to 7 days, mean arterial pressure rose progressively in all dogs, reaching a plateau 77 ± 8 (SE) mm Hg above control after 14 to 25 days. Hypertension was associated initially with further rise in both stroke volume and cardiac output, and peripheral resistance now became elevated. Four weeks after nephrectomy, peripheral resistance progressively became the predominant cause of elevated pressure while cardiac output returned toward control values. Absence of change in plasma volume and increase in mean circulatory pressure measured in a separate series of 7 dogs suggest that the initial increase in cardiac output preceding rise in pressure was due to enhanced venous return consequent to constriction of capacitance vessels. We conclude that increased cardiac output probably has a contributory role in the development of renal hypertension.
Direct Measurement of Intracardiac Blood Flow in Dogs with Experimental Ventricular Septal Defects
Authors: MESEL EMMANUEL
Published: June 2012

Experimental ventricular septal defects (VSD's) were produced in dogs under general anesthesia by excising a 9-mm core of tissue from the septum with a cylindrical cutting tool. A specially designed electromagnetic flow transducer was wedged into the defect compressing the septal tissue around it, thus causing all of the shunted blood to pass through the lumen. The sensing electrodes were in direct contact with the blood stream, allowing the transducer to be calibrated externally, and to be used as a primary standard of measurement. When left-to-right shunts were measured by the Fick technique, the average error was 57percnt; (2% to 154%). When pulmonary arterial oxygen saturation exceeded 85%, measurements using the Fick method showed errors greater than 30% (61% to 154%) in 9 of 11 animals. The VSD's were of moderate size and resulted in right ventricular systolic pressures between 1/4; and 1/2; of systemic. The flow pattern and the interventricular pressure difference were remarkably similar in contour. Delay in right ventricular activation occurred in most animals as a result of surgical disturbance of the conduction system. Diastolic shunting, which varied between 15% and 25% of the total, was noted in animals with or without changes in conduction pattern. The sequence of ventricular activation was an important factor in controlling systolic shunting and may be an important factor in the distribution of myocardial work.
Mechanics of Distension of Dog Veins and Other Very Thin-Walled Tubular Structures
Authors: MORENO AUGUSTO H. , KATZ ADOLPH I. , GOLD LOUIS D. , REDDY R. V.
Published: June 2012

We present first phenomenological characterizations of the pressure-volume relationships (a) in veins excised from dogs under anesthesia and (b) in thinwalled latex tubes. We measured their cross-sectional areas and perimeters from cinefluorographic enlargements during distension. From flattened to circular cross sections, the perimeter of latex tubes remained constant while the area increased exclusively by bending of the walls. Compliance was large in this regime. After circular cross sections were reached, further increases in area were associated with increments in perimeter and there was stretching of the wall. Compliance declined sharply. Veins did not show a distinct two-regime behavior but a combination of bending and stretching which extended the region of large compliance to values of transmural pressure of physiological interest. Using classical theory of elasticity, we propose mathematical relationships describing the proportionality between the pressure and the curvature of the wall during the regime where bending is the primary controlling mechanism. We mechanized these relationships on an analog computer and correlated the solutions with the physical experiments. We conclude that no modulus of elasticity, alone, can relate the pressure and the volume when bending is predominant. In this regime the significant quantity is the modulus of flexural rigidity.
Diastolic Geometry and Sarcomere Lengths in the Chronically Dilated Canine Left Ventricle
Authors: ROSS JOHN , SONNENBLICK EDMUND H. , TAYLOR ROGER R. , SPOTNITZ HENRY M. , COVELL JAMES W.
Published: June 2012

In 10 dogs left ventricular geometry and ultrastructure were examined 3 to 12 weeks after chronic ventricular dilatation was induced by means of a large arteriovenous shunt. Following cardiac catheterization, the hearts were arrested and fixed in diastole at the left ventricular end-diastolic pressures (LVEDP) which existed in the beating heart. Transmural LVEDP were increased in all animals (avg. 27 mm Hg). The diastolic pressure-volume relationship was shifted to the right, the average end-diastolic volume of the chronically dilated ventricles (avg. 103 ml) being larger than that of previously studied acutely dilated ventricles (avg. 72 ml,
P
<.01), but calculated diastolic wall stress values were not different. Sarcomere lengths in the chronically dilated hearts averaged 2.19±.02 µ (
SE
) (range 2.11 to 2.27), a value near the apex of the sarcomere length-tension curve, but not significantly different from sarcomere lengths in acutely dilated ventricles. Slippage between myofibrils, reflected by a loss of normal alignment of the Z lines, appeared to be one mechanism underlying this adaptation. The findings indicate that sarcomeres in the canine left ventricular wall are remarkably resistant to chronic as well as to acute overstretch. They further imply that little or no Frank-Starling reserve mechanism was available in these ventricles and raise the possibility that a descending limb of the heart's performance as a pump need not reflect a descending limb at the sarcomere level.
Conduction of the Cardiac Impulse
Authors: CRANEFIELD PAUL F. , HOFFMAN BRIAN F.
Published: June 2012

A segment of a bundle of canine Purkinje fibers was encased in agar made up in Tyrode solution containing elevated K
+
(47 m
M
) to depress the excitability of the segment. At a degree of depression producing total block of conduction in each direction through the depressed segment, exciting both ends of the bundle yielded full excitatory responses in the center of the depressed area. These responses arose with a long latency after excitation of the normal ends outside the depressed segment. Summation occurred over a long interval of relative timing of excitation of the ends. When excitation of one end alone produced a response in the center of the depressed segment, that response sometimes could be inhibited by stimulating the other end. In another preparation a branch emerged from the center of the depressed segment. Summation of excitation in the center of the depressed area resulted in conduction of activity out the branch at an interval appropriate to re-excite the entire heart. When one end of the preparation could excite the branch, stimulation of the other end sometimes inhibited excitation of the branch. The results are important as part of the explanation of phenomena associated with re-entrant arrhythmias.
Effects of Hypertension and Its Reversal on the Thoracic Aorta of Male and Female Rats
Authors: WOLINSKY HARVEY
Published: June 2012

Effects of hypertension and its reversal on the wall of the thoracic aorta of male and female rats were studied. Hypertension for 10 weeks caused increased diameter, wall thickness, tangential tension, wall stress, and medial area in both sexes. In addition, absolute amounts of elastin, collagen, and noncollagenous, alkali-soluble protein were significantly increased in the walls of all hypertensive vessels. Associated with the decrease of calculated tension and wall stress to normotensive levels after reversal of hypertension, wall thickness and medial area in males remained significantly greater than in controls and similar to the values found in hypertensive vessels, whereas in females these parameters returned fully to control levels. Absolute amounts of noncollagenous, alkali-soluble proteins did return to control levels after hypertension reversal, but elastin and collagen remained elevated in amounts similar to those in vessels with sustained hypertension; in females, this resulted in an above-normal concentration of these fibrous elements in the vessel wall. Compositional changes of the female vessel wall after reversal of hypertension were thus similar to but more clearcut and complete than those found in the male aorta. Recognition of irreversible changes in vessels subjected to hypertension may have implications for the benefits to be gained from blood pressure reduction on the progression of cardiovascular disease.
DNA Synthesis and Mitoses in Coronary Collateral Vessels of the Dog
Authors: SCHAPER WOLFGANG , DE BRABANDER MARC , LEWI PAUL
Published: June 2012

DNA synthesis and mitotic activity in coronary collateral arterioles was assessed in dogs at different time intervals after gradual ameroid constriction of the left circumflex coronary artery. Labeling of nuclei and the mitotic index were highest at 3 weeks after implantation of the constrictor and gradually declined thereafter. Labeling persisted for at least 8 weeks but radioactive DNA was not found 12 months after coronary artery constriction nor in controls or animals with sham operations. Proliferative activity was, at any time interval, highest at the level of the smallest diameters of the collateral vessels. Labeled nuclei and mitoses were found in endothelial, medial, and adventitial cells. Myocardial mesenchymal cells also incorporated tritiated thymidine. The data provide evidence that after constriction of a major coronary artery, the coronary collateral vessels enlarge by an active growth process that follows the basic laws of cell kinetics.
Compliance of the Human Pulmonary Arterial System in Disease
Authors: Reuben Stuart R.
Published: June 2012

Pulmonary arterial and pulmonary arterial "wedge" pressures were measured in 35 patients during cardiac catheterization. Pulmonary arterial compliance (C) was calculated from the diastolic pulmonary arterial pressure profile, left atrial pressure, and pulmonary vascular resistance (R). In the pulmonary normotensive group, compliance averaged 2.87 ml/mm Hg; in patients with severe pulmonary hypertension, values as low as 0.7 ml/mm Hg were found. In 16 of these patients, pulmonary capillary blood flow was measured by N
2
O body plethysmography. In pulmonary normotensive patients the pulsatility of capillary flow, i.e., the ratio of peak-to-mean flow rates, was 2:1; advanced pulmonary hypertension was associated with values as low as 1.2:1, suggesting marked damping of the flow pulse. The pulsatility index correlated well with the RC time constant of the pulmonary arterial system, so that damping of the pulmonary capillary flow pulse was associated with a prolonged time constant. This suggested that in severe pulmonary hypertension the pulmonary arterial walls are stiff and indistensible. A method was developed for estimating mean pulmonary arterial and left atrial pressure from the pulmonary capillary flow pulse, and the relationships between compliance and pressure and pulsatility index and RC time constant. N
2
O-plethysmography can thus provide a reliable and repeatable, noninvasive method for investigation of the pulmonary vascular bed.
Effect of Low Frequency Vibration on the Arterial Wall
Authors: Boughner Derek R. , Roach Margot R.
Published: June 2012

Poststenotic dilation is accompanied by alteration of the elastic properties of the arterial wall in the region where a murmur occurs. The low frequency vibrations contained in a murmur may cause the changes observed. Isolated human external iliac arteries were distended with 100 mm Hg pressure and vibrated with specific frequencies from 30 to 400 Hz. When dilation occurred, the radius increased at a rate of 7.1±3.4
SD
% per day. However, for each artery, dilation tended to occur with one frequency in preference to others. The amplitude, as long as sufficient to produce vibration of the wall, was not important in determining this tendency. The older the artery the higher the frequency necessary to produce dilation. Young vessels, under 45 years, responded best to frequencies <100 Hz, and vessels 45-60 years old responded to frequencies 100-200 Hz and older vessels, >60 years, dilated with frequencies >200 Hz. The elastic diagram of the vessel after dilation showed the major change to be in the elastin component of the arterial wall rather than the collagen. These findings correspond to those seen in a vessel displaying poststenotic dilation.
Significance of Splanchnic Proteases in the Production of a Toxic Factor in Hemorrhagic Shock
Authors: Glenn Thomas M. , Lefer Allon M.
Published: June 2012

The pathogenesis of circulatory shock has been previously associated with the plasma accumulation of a myocardial depressant factor (MDF). The plasma accumulation of MDF in cats subjected to hemorrhagic shock was associated with marked increases (P <0.01) in activities of plasma cathepsins A-B. The pH optima for three of the five cathepsins were in the range of 4.8-5.2, a pH range close to that found intracellularly during shock. Moreover, pancreatic and hepatic tissue from these cats exhibited significant decreases in total specific activities for these enzymes, compared with minimal changes in heart, duodenum and spleen. Decreases in total pancreatic cathepsin activities were associated with marked ultrastructural changes in pancreatic acinar cells primarily characterized by vacuolization of the lysosomes. Incubation of homogenates of splanchnic viscera of unshocked dogs revealed that significant concentrations of MDF were produced only in incubated pancreatic homogenates. Infusion of MDF in amounts half that produced by a cat pancreas into intact anesthetized cats yielded a significant circulatory depression indicated by a progressive decline in cardiac output and mean arterial blood pressure and a 54% decrease in cardiac work performance within 60 minutes. These data indicate that substantial amounts of lysosomal proteases are released during shock and that they operate in a suitable pH range to account for the production of quantities of MDF that are sufficient to induce a marked degree of cardiac depression.
Muscle Cholinergic Dilators in the Sinus Baroreceptor Response in Cats
Authors: Takeuchi Toru , Manning John W.
Published: June 2012

Experiments were done to evaluate the effect of the cholinergic vasodilator system on the flow-pressure relation in the isolated, perfused gastrocnemius and soleus muscles of the cat. Reflex changes in the muscle vascular resistance were produced by maintaining the isolated, perfused carotid sinus at different pressure levels. Flow-pressure curves were obtained from the isolated muscles at high, medium, and low carotid sinus pressures before and after administration of adrenergic or cholinergic blocking drugs or denervation, or both. Following cholinergic receptor blockade, flow-pressure relations at high sinus pressure showed a loss of a dilator component, hut curves at low and medium sinus pressures were the same as controls. Following adrenergic receptor blockade, flow-pressure curves at low and medium sinus pressures were superimposed; however high sinus pressure still produced a decrease in vascular resistance. The remaining vasodilation could be abated by either denervation or anticholinergic agents. The difference between the untreated and the cholinergically blocked flow-pressure responses represented 15-30% of the range of change in vascular resistance evoked by the sinus baroreceptor reflex. Thus, effective withdrawal of sympathetic vasoconstrictor tone did not account for total vasodilation. The data indicate that the sympathetic cholinergic vasodilator system participated in the vascular responses of skeletal muscle during baroreceptor stimulation.
Intrarenal Conversion of Angiotensin I to Angiotensin II in the Dog
Authors: Salvo Joseph Di , Peterson Aron , Montefusco Cheryl , Menta Margaret
Published: June 2012

Effects of close intra-arterial injections of angiotensins I and II on changes in renal blood flow and renal vascular resistance were studied in dogs anesthetized with pentobarbital sodium. In the first series of experiments, angiotensin I (0.375 µg) or angiotensin II (0.13 µg) decreased renal blood flow and pressures in a small renal cortical vein and the renal vein. Although renal vascular resistance was markedly increased by angiotensins I or II, these increases did not appear to involve renal venous segments. Responses to angiotensin I occurred when the injected agonist was not allowed to reach the systemic circulation, and were virtually abolished during infusion of SQ 20475, a synthetic pentapeptide (Pyr-Lys-Try-Ala-Pro) that inhibits enzymatic conversion of angiotensin I to angiotensin II. In the second series of experiments, renal vascular responses to intra-arterial injections of angiotensin I (0.375-3.75 µg) and angiotensin II (0.13-1.00 µg) were studied. Responses to angiotensin I, but not those to angiotensin II, were significantly attenuated by SQ 20475. The results suggest that similar renal vascular segments respond to angiotensins I and II. Responses to angiotensin I are probably due to its intrarenal conversion to angiotensin II. Such conversion appears to occur to the extent of about 4%.
Effect of Age and High Blood Pressure on Barorefiex Sensitivity in Man
Authors: Gribbin Brian , Pickering Thomas G. , Sleight Peter , Peto Richard
Published: June 2012

The purpose of this study was to relate baroreflex sensitivity to age and arterial pressure in 61 male and 20 female untreated subjects, aged 19-66 years, whose mean arterial pressures ranged from 70 to 150 mm Hg. In this selected group of subjects there was no correlation between age and arterial pressure. The index of sensitivity used was the increase in pulse interval which occurs reflexly in response to a rise in systolic pressure induced by the intravenous injection of phenylephrine and is measured as the increase in pulse interval in milliseconds per mm Hg rise in systolic blood pressure. It ranged from 1.9 to 48.9 msec/mm Hg. Increasing age and arterial pressure act independently to reduce baroreflex sensitivity. Eight subjects who had normal blood pressure at the time of testing but whose pressure had been elevated in the past, had reflex sensitivities significantly less than expected in persons of the same age and mean arterial pressure. The heart rate in these subjects was not significantly different from that in the controls; the heart rate of the 12 hypertensive subjects aged under 40 years was significantly faster than that of age-matched normotensive subjects but not that of older hypertensive subjects.
Repair in Arterial Tissue
Authors: Helin P. , Lorenzen I. , Garbarich C. , Matthienen M. E.
Published: June 2012

Male albino rabbits were subjected to a single mechanical dilatation of the descending thoracic aorta with a balloon catheter. The animals were killed 3, 6, 14, 30, and 60 days later. Between the sixth and the fourteenth days after injury, all the aortas which had been dilated developed severe, gross arteriosclerosis. Microscopic examination showed destruction and degeneration in the form of necrosis and calcification as well as regeneration and repair including new formation of cells, intercellular substance, and fibers. Biochemical and histochemical analyses revealed an early increase in hyaluronic acid and water followed by an increase in chondroitin-4, 6-sulfate and a later increase in heparan sulfate, dermatan sulfate, and collagen. These alterations were related to the focal lesions in the aortic wall. The permeability of the aorta to
125
I-albumin increased to a maximum 3 days after the dilatation, whereupon it decreased rapidly. The alterations were interpreted as nonspecific processes of repair in the vascular connective tissue. The pronounced dependence of the alterations on the time elapsed after injury must be considered in the study of vascular diseases where injury and repair may be involved.