bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Exercise on Coronary Tree Size in the Rat
Authors: STEVENSON JAMES A. F. , FELEKI VERA , RECHNITZER PETER , BEATON JOHN R.
Published: June 2012

Using the vinyl acetate corrosion cast technique devised by Tepperman and Pearlman, it has been demonstrated that, in the rat, forced physical exercise (treadmill or swimming) causes an increase in apparent coronary tree size provided the exercise is not too strenuous or frequent.
Observations on the Role of Diminished Oxygen Tension in the Functional Hyperemia of Skeletal Muscle
Authors: ROSS JOHN , KAISER GERARD A. , KLOCKE FRANCIS J.
Published: June 2012

The hypothesis that lowered tissue oxygen tension acting on vascular smooth muscle can explain functional hyperemia in skeletal muscle was examined in ten dogs. A comparison was made between the blood flow increment that accompanied rapid, rhythmic contraction of a gastrocnemius muscle and the flow change that occurred in the same muscle at rest during its perfusion with venous blood obtained from the resting or contracting gastrocnemius muscle of the opposite leg. Blood P

O
O2

, pH, and P

CO
CO2

were measured in samples of venous blood from the muscle. There was no evidence that the perfusion circuit traumatized the perfused blood. During functional hyperemia, the increases in blood flow averaged 173%, and the average venous P

O
O2

, was 25 mm Hg. During venous perfusion, the maximum increases in blood flow averaged 56%, and the average venous P

O
O2

, was 23 mm Hg. When the muscle was stimulated to contract during its perfusion with venous blood, increases in blood flow occurred which averaged 143%, despite additional falls in venous blood P

O
O2

that averaged only 3 mm Hg. These studies suggest that the effect of lowered P

O
O2

on vascular smooth muscle does not produce sufficient vasodilatation to explain functional hyperemia in skeletal muscle.
Spontaneous Arteriosclerosis of the Mesenteric, Renal, and Peripheral Arteries of Repeatedly Bred Rats
Authors: WEXLER BERNARD C. , Kwallek Jo tee , Conatser Dilman
Published: June 2012

Repeatedly bred male and female rats develop arteriosclerosis spontaneously. The arteriosclerosis appears to be accelerated by breeding because virgin rats of comparable age do not develop arterial disease. The arterial lesions begin in the abdominal aorta and consist of subendothelial swelling, mucopolysaccharide accumulation and eventual fibrosis. With continued, active breeding, the arterial lesions continue to increase in severity in the abdominal aorta, becoming grossly visible in the female breeder and of microscopic proportions in the male breeder.

Concomitant with the increasing severity of arteriosclerosis in the abdominal aorta, the mesenteric arteries and the visceral branches also show increasing numbers of arterial lesions. The lesions in the mesenteric and visceral branches are of varied morphology. The main renal artery, for example, shows fibromuscular dysplasia, its hilar portion displays intimal basophilia and elastosis and the intrarenal branches develop intimal cushions.

The male breeder develops severe, grossly visible lesions in the proximal portions of the iliac arteries, the lesions becoming less complex distally. The female breeder shows no grossly visible lesions in the iliac arteries but arteriosclerosis is severe throughout the length of the arteries to the extremities, the severity of these lesions being proportional to the arteriosclerosis in the abdominal aorta and its branches.
Reduction by Hyperbaric Oxygenation of the Mortality from Ventricular Fibrillation Following Coronary Artery Ligation
Authors: CHARDACK WILLIAM M. , GAGE ANDREW A. , FEDERICO ANTHONY J. , CUSICK JOHN K. , MATSUMOTO PAUL J. H. , LANPHIER EDWARD H.
Published: June 2012

The effect of the inhalation of hyperbaric oxygen on the incidence of ventricular fibrillation following ligation of the circumflex coronary artery was studied in 151 dogs weighing 17 kg or more.

Fifty-two per cent of the animals in the control group (room air, 1 atm abs) survived the challenge of this ligation. Survival increased to 60.4, 70, and 77.8% in the groups given 100% oxygen at an ambient pressure of 1, 2, and 4 atm abs, respectively. The orderly progression in the proportion of survivals is impressive but only approaches statistical significance.

The results of these experiments are less dramatic than those previously reported by others. They do point out the need for cautious clinical trial in rigidly controlled series.
Neurogenic Hypertension in the Rat
Authors: KRIEGER EDUARDO M.
Published: June 2012

Several techniques of radical denervation of the sino-aortic depressor areas were tried in order to produce a permanent neurogenic hypertension in the rat. The aortic depressor fibers were interrupted at the neck level by resecting the nerves which usually exhibit baroreceptor activity, namely, isolated aortic nerve, sympathetic, and laryngeal nerves. The carotid sinus was denervated by stripping the carotid bifurcation and painting with phenol. When the carotid bifurcation was resected bilaterally, in a one-stage operation, all rats showed symptoms of cerebral ischemia, dying shortly thereafter.

Isolated denervation of the aortic baroreceptors was followed by a transitory hypertension. No changes in preasure were observed when only the carotid sinuses were denervated. A few rats in which the usual baroreceptor pathways were interrupted, except the superior laryngeal nerve, developed chronic hypertension. Yet, to obtain consistently permanent hypertension it was necessary to include in the denervation every baroreceptor route.

A simple one-stage operation for complete sino-aortic baroreceptor denervation is described. This procedure was used in 140 rats that were then studied for periods up to one year. All the operated animals presented some degree of hypertension. Blood pressure measurements made during the first week showed even then that the rats were hypertensive. This observation suggests that in the rat no latent period for the appearance of neurogenic hypertension is present. Hypertension was permanent in 75% of the rats observed up to one year; blood pressure returned to normal values in the remaining 25%, usually after the third month. Extirpation of the adrenal medulla had no effect on the evolution of the hypertension in the denervated rats.

Blood pressure was measured repeatedly in unanesthetized rats by tail plethysmography. Pressure values determined by this method, though 10 to 20 mm Hg lower, approximated the mean arterial pressure recorded directly from the femoral artery in normotensive and hypertensive rats. The hypertension in denervated rats included an increase of systolic as well as diastolic pressure. The heart rates of quiet hypertensive rats were within the normal range and, in general, no close correlation was observed between increases in blood pressure and elevations in heart rate. Normal rats have marked fluctuations in both pressure and heart rate when walking or when stimulated; these fluctuations were much greater in the neurogenic hypertensive animals. Moreover, the hypertensive rats showed large oscillations of blood pressure synchronous with respiratory movements particularly when the latter were slower and deeper than normal.

The rats seemed to tolerate both the denervation and the hypertension very well. Histological examination of tissues from hypertensive rats showed myocardial hypertrophy and a thickening of the basement membrane of the glomerular capsule. The severity of the latter abnormality was closely associated with the duration of the hypertension.
Hemodynamic Determinants of the Amplitude of the First Heart Sound
Authors: SAKAMOTO TSUGUYA , KUSUKAWA REIZO , MACCANON DONALD M. , LUISADA ALDO A. , Harvey Ivan
Published: June 2012

The relationships between the amplitude of the first heart sound and various hemodynamic parameters and their analog functions were systematically investigated in 51 dogs under morphine and pentobarbital anesthesia. Simultaneous hemodynamic and phonocardiographic tracings were obtained by cardiac catheterization, high speed recording, and analog computers. Changes in cardiodynamics were induced by:
l
-epinephrine, levarterenol, phenylephrine, isoproterenol, methoxamine, veratrine, vasopressin, histamine, atropine, saline infusion, mechanical obstruction of the aorta, pulmonary artery, or both venae cavae, embolization of the coronary arteries with plastic microspheres, mechanical rupture of aortic valve leaflets, or hemorrhage. In this way, the relationships were examined over a wide range of pressures, volumes, and cardiodynamics. The results showed that the amplitude of the first sound is not directly related to stroke output, P-R interval, heart rate, end diastolic, or systolic ventricular or aortic pressures. Only the peak rate of rise of left ventricular systolic pressure (first derivative maximum) had a consistent relationship to first sound amplitude. The right ventricle seems to contribute very little to the external first sound. These observations suggest that the amplitude of the first sound is related to left ventricular contractility.
Validity of the Xenon
133
Method for Measurement of Muscle Blood Flow Evaluated by Simultaneous Venous Occlusion Plethysmography
Authors: LASSEN NIELS A. , LINDBJERG IB F. , DAHN INGE
Published: June 2012

Calf blood flow has been measured simultaneosuly by the Xe
133
clearance method in m. tibialis anterior and m. gastrocnemius and by venous occlusion plethysmography in normal man and in patients with intermittent claudication.

At rest Xe
133
muscle blood flow (
MBF
xe
) averaged 1.6 ml/100 g/min while plethysmographic total calf blood flow (calf BF) was higher in each instance and averaged 3.0 ml/100 g/min. There was no difference between normal legs and legs with occlusive vascular disease in this respect.

Following one to five minutes of arterial occlusion, reactive hyperemia was seen with both methods, the rapid changes being most readily observed with the plethysmographic method.

After exhaustive muscular exercise during ischemia in normal man maximal
MBF
xe
averaged 40 ml/100 g/min (48 ml/100 g/min over m. tibialis anterior and 32 ml/100 g/min over m. gastrocnemius). The maximal calf BF averaged 42 ml/100 g/min. The rate of return of blood flow to the resting level was also quite similar with both methods. In the patients with claudication both methods showed a subnormal and delayed hyperemic reaction following ischemic work, but the
MBF
xe
was consistently lower.

The results obtained indicate that the Xe
133
modification of Kety's local clearance method for measurement of muscular blood flow in man is essentially valid.
Endocardial Fibroelastosis of Large Mammals
Authors: BLACK-SCHAFFER B. , GRINSTEAD CARL E. , BRAUNSTEIN JOHN N.
Published: June 2012

Normal hearts of a mouse, rat, man, sea lion, hippopotamus, elephant, and blue whale were shown to have different numbers of myocardial fibers, 10
7
to 10
13
, based on calculations involving their myocardial fiber diameters and nuclear density counts. These two parameters did not vary greatly in the different species. However, their heart weights ranged from 10
-1
to 10
5
g. The larger mammals have endocardial fibroelastosis of their hearts and very thick aortas. These anatomic findings were explained by employing principles of hydrostatics and proposing that elastic tissue is required to help withstand the high mural tension resulting from the long radii and the hydrostatic pressures in the heart chambers and aortic lumen.
Pulmonary Vascular Impedance in the Dog
Authors: BERGEL DEREK H. , MILNOR WILLIAM R.
Published: June 2012

Pulmonary vascular hydraulic input impedance was measured in 13 anesthetized openchest dogs with normal sinus rhythm, and 2 dogs with surgically induced atrioventricular block, by means of electromagnetic flowmeters and strain gauge manometers of known frequency response. The linearity of the pulmonary bed was evaluated by measuring impedance while the heart rate, and hence the pulsatile input to the bed, was varied.

The pulmonary bed behaved as a quasilinear system, within the limits of accuracy of the methods employed and the range of frequencies tested. The use of input impedance, or oscillatory pressure/flow ratio, to describe some characteristics of the bed is therefore justifiable, and analogies with linear models like the simple transmission line are not unreasonable.

The characteristic input impedance averaged 3,094 dyne sec cm
-5
kg, or about one-third the magnitude of the pulmonary vascular resistance, and was therefore a significant part of the total opposition that must be overcome in moving blood through the lungs. This impedance to pulsatile flow is not included in calculations of resistance from mean pressure and flow measurements.

The pattern of the impedance spectrum suggested that reflections originating from arteries 1.0 mm and less in diameter play a large role in determining input impedance and its variations with frequency. Pulmonary vasoconstriction by 5-hydroxytryptamine (serotonin) altered the impedance pattern in a manner consistent with increased wave reflection and displacement of the dominant reflecting sites to positions nearer the main pulmonary artery. Capillary compression by increased intra-alveolar pressure also increased reflection, but did not alter the sites of reflection significantly, providing further evidence that the normal impedance pattern and its modification by serotonin are both determined by the characteristics of the arterial part of the bed.
Mechanism of Norepinephrine Depletion in Experimental Heart Failure Produced by Aortic Constriction in the Guinea Pig
Authors: SPANN JAMES F. , CHIDSEY CHARLES A. , POOL PETER E. , BRAUNWALD EUGENE
Published: June 2012

The present study was undertaken to evaluate the influence of heart failure on the cardiac stores of norepinephrine, and to elucidate the mechanisms responsible for the changes observed. Congestive heart failure was produced in the guinea pig by supravalvular aortic constriction. Significant reductions in both the concentration and content of norepinephrine in the ventricles were observed, the magnitude of changes being related to the severity of the constriction. The renal concentration of norepinephrine was not usually affected. Infusions of large quantities of norepinephrine produced elevations of ventricular norepinephrine concentrations which were significantly less in guinea pigs with heart failure than in normal animals. Injections of lesser quantities of radioactive norepinephrine also resulted in smaller amounts of this material in the hearts of animals with failure. Measurement of the decay of specific activity indicated that heart failure did not alter the net turnover of norepinephrine in the left ventricle. From these findings it has been concluded that a defect in the uptake and/or retention of norepinephrine exists in these hearts and that this defect may be responsible for the depletion of norepinephrine.
Effect of Atrial and Ventricular Tachycardia on Cardiac Oxygen Consumption
Authors: BADEER HENRY S. , FEISAL KHALIL A.
Published: June 2012

Atrial tachycardia and ventricular tachycardia were induced by electric stimuli applied to the heart in the modified dog heart-lung preparation. Cardiac oxygen consumption was measured by the direct Fick method. Left ventricular output was kept constant at about 900 ml/min and arterial pressure at 100 mm Hg during both atrial and ventricular pacing. An increase of heart rate from 130 to 157 beats per minute in atrial tachycardia, and from 130 to 158 beats per minute in ventricular tachycardia, increased cardiac oxygen uptake by 11.5% and 50% respectively (mean of seven experiments). The greater energy expenditure of the heart in ventricular tachycardia, when compared with atrial tachycardia at equivalent heart rates, was attributed to the asynchrony of fractionate contractions of the ventricular muscle when stimuli are applied to the ventricular surface. Total coronary flow increased in both types of tachycardia, but more in ventricular tachycardia.
Measurement of Renin Activity in Human Plasma
Authors: PICKENS PETER T. , BUMPUS F. MERLIN , LLOYD A. MURRAY , SMEBY ROBERT R. , PAGE LRVINE H.
Published: June 2012

A method is described for estimating plasma renin activity by using renin substrate present in plasma. This method differs from other indirect renin assay methods by (1) incubation in the absence of ions thus establishing conditions for zero order kinetics for the reaction between endogeneous renin and substrate and (2) the use of angiotensinase inhibitors di-sodium ethylenediamine tetraacetic acid (
EDTA
) and d-isopropylfluorophosphate (DFP). Recoveries of renin added to plasma in levels similar to those occurring in plasma are 85%
SD
±7%.

The incubation was done at pH 5.5 which was shown to be the optimum for human renin reacting with human substrate.

By incubating human plasma samples with known quantities of human renin, evidence was obtained suggesting that factors other than enzyme or total substrate concentrations affect the velocity of angiotensin formation. This variability of reaction rate may be explained by the existence of an inhibitor or activator in this system or by a variation in the type of substrate.
Cardioversion and Digitalis Drugs: Changed Threshold to Electric Shock in Digitalized Animals
Authors: LOWN BERNARD , KLEIGER ROBERT , WILLIAMS JAMES
Published: June 2012

The relationships between the action of digitalis drugs and the effects of cardioversion were studied in 44 dogs. Ventricular tachycardia provoked by either acetyl strophanthidin (AS) or ouabain could not be reverted to sinus rhythm by DC shock. When ventricular fibrillation was induced electrically during digitalis toxicity, defibrillation could be accomplished readily but the toxic arrhythmia due to digitalis remained unaltered. When ventricular fibrillation was induced by AS, it was also unaffected by repeated high energy discharges.

In control animals the median energy to produce ventricular tachycardia by electrical discharge was 400 watt-seconds. Repeated electrical shocks did not change the level of energy required to produce ventricular tachycardia. However, following recovery from ouabain-induced ventricular tachycardia, the electrical threshold for ventricular tachycardia was 0.2 watt-second. A similar but less consistent response was noted after AS-induced ventricular tachycardia. The sensitization to electrical shock lasted for five to ten minutes after AS and for approximately one hour after recovery from ouabain toxicity. This same phenomenon of sensitization to electrical discharge was observed during digitalization. About 80% of the potentially toxic dose of ouabain had to be administered before the electrical threshold was lowered.

The sensitivity to DC shock in the digitalized animal was not related to any specific phase of the cardiac cycle. Digitalization did not change the duration, location or energy limits of the ventricular vulnerable period.

These experiments lead to the following conclusions of clinical importance: 1) Cardioversion will not be effective in arrhythmias induced by digitalis toxicity and 2) in the presence of overdigitalization cardioversion discharge may provoke serious disturbance of rhythm.
Contractile State of the Heart Characterized by Force-Velocity Relations in Variably Afterloaded and Isovolumic Beats
Authors: Ross John , Covell James W. , Sonnenblick Edmund H. , Braunwald Eugene
Published: June 2012

Relations between tension and the velocity of shortening in the intact left ventricle of the dog were examined in a manner analogous to that employed in isolated muscle, i.e., by serial, reproducible variations in the afterload alone, from a constant end diastolic volume. Sudden increases or decreases in the aortic pressure during diastole were produced, and ejection rate was measured with an electromagnetic flowmeter; LV wall tension and the shortening velocities of the myocardial fibers and the contractile elements were then calculated. By analyzing isovolume points early in ejection, effects resulting from two other determinants of shortening velocity, duration of active state and instantaneous muscle length, were minimized. Shifts in the basic force-velocity relation with alterations in V
max
, obtained by extrapolation, and maximum tension were clearly demonstrated. Norepinephrine and paired electrical stimulation caused a shift in this relation to the right, with increases in velocity at any tension, and acute heart failure produced a shift to the left, with decreases in velocity at any tension. Similar shifts were also apparent in curves relating tension to velocity, calculated during single isovolumic contractions. It was suggested that determination of these relations expands traditional definitions of ventricular performance, and that estimation of changes in maximum velocity as well as maximum strength relative to muscle length provides direct information concerning alterations in the contractile state of the intact heart.
Hormonal Control of Collateral Circulation
Authors: Meffert William , Liebow Averill A.
Published: June 2012

The possible regulatory effects of growth hormone and of cortisone on the development of pulmonary collateral vessels after ligation of one pulmonary artery were investigated in the rat. The weights of the animals were regulated so that they did not differ significantly in the control and experimental groups at the end of the experiment. The extent of the collateral circulation was judged by visual inspection and by weighing the casts. Animals injected with cortisone acetate intramuscularly in doses of 5 mg daily for two weeks and then maintained on an average dose of 15 mg weekly, had less development of collateral circulation at four and eight weeks than did controls. Animals injected with growth hormone in doses of 0.1 mg daily, had significantly larger collaterals than did controls at eight but not at four weeks, as determined by the visual ranking method. These results indicate 1) that there can be chemical control of collateral circulation, and 2) that cortisone and growth hormone can influence the development of collateral vessels in part by mechanisms other than an effect on body weight.
Effect of Velocity Gradient on the Clotting Time of Blood and on the Consistency of Clots Formed in Vitro
Authors: Dintenfass Leopold
Published: June 2012

Clotting times of human blood and rheology of blood clots have been determined by means of a cone-in-cone viscometer, a ring-in-ring adapter, and a variable-frequency thromboviscometer. The last represents a variable frequency version of the thrombelastograph.

The results of clotting time tests on blood samples from 118 donors indicate clearly that clotting time is a function of the velocity gradient at which clotting takes place. Clotting time decreases as the velocity gradient increases.

Consistency of blood coagula depends on the velocity gradient at which coagula are formed. Consistency, or viscosity, of coagula decreases when the velocity gradient increases. While the viscosity of clots formed at low rates of shear is of the order of 100 poises, coagula formed at intermediate rates of shear exhibit viscosity of a few decipoises. Viscosity of blood is not significantly altered if coagulation takes place at rates of shear near 400 sec
-1
.
Functional Distribution of Right and Left Stellate Innervation to the Ventricles
Authors: Yanowitz Frank , Preston James B. , Abildskov J. A.
Published: June 2012

Changes of the electrocardiogram and of ventricular refractory period were measured following either unilateral stellate ganglion stimulation or ablation in the open chest dog preparation.

Right stellate ganglionectomy or left stellate stimulation produces prolonged Q-T intervals and increased T-wave amplitude. Left stellate ganglionectomy or right stellate stimulation produces increased T-wave negativity without measurable change in the Q-T interval.

The differing patterns of electrocardiographic wave form resulting from changes in sympathetic tone mediated by right and left stellate innervation could be correlated with changes in ventricular refractory period. Following right stellate ganglionectomy, refractory period prolongations were most marked over the anterior ventricular surface; left stellate ganglionectomy produced the greatest prolongation on the posterior surface.

Although the right and left stellate innervations of the ventricles overlap, the left stellate influence is predominant over the posterior wall of the ventricles, while right stellate influence dominates the anterior ventricular walls.

The electrocardiographic form changes observed following unilateral alteration of sympathetic tone paralleled those electrocardiographic abnormalities seen in patients with lesions of the central nervous system, suggesting a possible functional explanation for these clinical findings.
Hemodynamic and Metabolic Effects of Hemorrhage in Man, with Particular Reference to the Splanchnic Circulation
Authors: Price Henry L. , Deutsch Stanley , Marshall Bryan E. , Stephen George W. , Behar Marjam G. , Neufeld Gordon R.
Published: June 2012

1. Eleven normal subjects were studied before and after removal of 15 to 20% of their blood volume within 35 minutes.

2. This amount of blood loss did not produce conspicuous effects upon any of the usually measured circulatory or metabolic parameters.

3. The results suggest that the splanchnic circulation functions as an important blood reservoir in man, that it can be preferentially depleted of blood by a mechanism which does not automatically increase vascular resistance, and that the ability of our subjects to tolerate blood loss was attributable in large part to this response.
Specialized Conducting Fibers in the Interatrial Band
Authors: Wagner Michael L. , Lazzara Ralph , Weiss Robert M. , Hoffman Brian F.
Published: June 2012

The interatrial band (Bachmann's bundle) was studied both in situ, in the adult dog, and in vitro, using excised canine atria. Electrograms recorded from this structure in the intact animal had a double intrinsic deflection during sinus rhythm, and responded to rapid rates of atrial stimulation with alternation in both configuration and cycle length. Potassium infusions which produced atrial arrest with a sinoventricular rhythm did not abolish electrical activity in the interatrial band.

Single fibers of the interatrial band, studied in vitro with microelectrodes, had distinctive transmembrane potentials different from those of ordinary atrial muscle fibers. Action potentials were characterized particularly by a high rising velocity (maximum dv/dt), of the same magnitude as that recorded from Purkinje fibers, and a prominent plateau. These fibers were sensitive to acetylcholine and more resistant to potassium arrest than ordinary atrial fibers. Conduction velocity in the interatrial band was consistently higher than in ordinary atrial muscle. Plots of sequential activation time against linear distance showed different conduction velocities in parallel linear paths, with the highest velocity in the path on the crest of the interatrial band. Due to rapid conduction through the interatrial band, simultaneous activation of right and left atrial points was demonstrated.

It is concluded: 1) The interatrial band is not a homogeneous structure, but contains two fiber types. 2) In addition to ordinary atrial muscle, specialized conducting fibers are present in the interatrial band. 3) Impulse spread in the interatrial band is not radial or uniform. Rather, it occurs through several linear paths which probably have infrequent cross-connections.
Inhibition of Protein Synthesis in Cardiac Hypertrophy and its Relation to Myocardial Failure
Authors: Zühlke Volker , du Mesnil de Rochemont Wolfgang , Gudbjarnason Sigmundur , Bing Richard J.
Published: June 2012

The rate of myocardial protein synthesis was studied in hearts of rabbits with experimentally produced cardiac hypertrophy and treatment with actinomycin D and puromycin as well as in animals maintained on a protein-free diet. Actinomycin D and puromycin inhibited myocardial incorporation of glycine-2-C
14
only if protein synthesis was stimulated by means of aortic stenosis. Actinomycin D had no effect on the normal myocardium. Animals on protein-free diet also showed a decreased rate of glycine-2-C
14
uptake into heart muscle protein after production of aortic stenosis, but an increased incorporation into skeletal muscle protein. Inhibition of protein synthesis during the first stage of cardiac hypertrophy was associated with the development of heart failure, regardless of whether the inhibition occurred as a result of actinomycin D, of puromycin or of protein-free diet. As compared to animals maintained on a regular diet, myocardial protein turnover rate in unoperated animals was not altered significantly by protein-free diet.
Circulatory Effects of Acute Expansion of Blood Volume:
Authors: ROBINSON BRIAN F. , EPSTEIN STEPHEN E. , KAHLER RICHARD L. , BRAUNWALD EUGENE
Published: June 2012

The maximum cardiac output that can be achieved during exercise might be limited either by extracardiac factors influencing ventricular filling, or by the heart itself. In order to investigate this problem, the effect on the cardiac response to maximum exertion of an acute expansion of blood volume was studied in six men with essentially normal cardiovascular systems. Augmentation of blood volume produced by infusion of 1000 to 1200 ml of the subject's own blood resulted in a small increase in central venous pressure at rest (avg = + 1.9 mm Hg) and a substantial increase in cardiac output (avg = + 1.47 liters/min). During exercise, however, the expansion of blood volume caused a large increase in central venous pressure (avg = + 7.4 mm Hg), but no significant increase in cardiac output or maximum O
2
uptake. This finding suggests that the maximum cardiac output is not restricted by extracardiac factors and that the upper limit must therefore be determined by the heart itself.
Release of Adenosine from Anoxic Hearts
Authors: KATORI MAKOTO , BERNE ROBERT M.
Published: June 2012

In the presence of 8-azaguanine, an inhibitor of adenosine deaminase, adenosine appears in the perfusate of isolated cat and guinea pig hearts subjected to anoxia or severe hypoxia. With graded hypoxia the increase in coronary flow is roughly proportional to the sum of adenosine, inosine and hypoxanthine released from the hearts and inversely related to the oxygen tension of the perfusion fluid. Addition of epinephrine to oxygenated perfusion medium yields results similar to those obtained with hypoxia. These findings are compatible with the concept that vasodilation observed with hypoxia is due to adenosine formed from the breakdown of myocardial adenine nucleotides.
Effect of Propranolol on Systemic and Coronary Hemodynamics at Rest and during Simulated Exercise
Authors: MCKENNA DAVID H. , CORLISS ROBERT J. , SIALER SALVADOR , ZARNSTORFF WILLIAM C. , CRUMPTON CHARLES W. , ROWE GEORGE G.
Published: June 2012

The systemic and coronary hemodynamic effects of relatively large doses of propranolol have been studied following its infusion into intact anesthetized dogs at rest and during simulated exercise. At rest, the administration of propranolol was associated with decreased cardiac output and ventricular work and increased peripheral, pulmonary, and coronary vascular resistances. Coronary blood flow and coronary sinus oxygen content decreased while myocardial oxygen consumption and the index of cardiac efficiency were unchanged. The usual hemodynamic response to mild exercise was obtained, with increased cardiac output, cardiac work, body oxygen consumption, and a modest but insignificant increase in coronary blood flow. When propranolol was given and the same exercise continued, body oxygen consumption, cardiac output, and left ventricular work significantly decreased. Insignificant decreases occurred in coronary blood flow, left ventricular oxygen usage, and coronary sinus oxygen content. The present observations are consistent with the thesis that beta-adrenergic blockade induced by propranolol decreases cardiac work at rest and reduces the cardiovascular response to exercise.
Contraction of Vascular Smooth Muscle in Response to Plasma
Authors: BOHR DAVID F. , JOHANSSON BÖRJE
Published: June 2012

Addition of plasma to the physiologic salt solution in which helical strips of vascular smooth muscle were suspended caused the muscle to contract. The plasma was obtained from dog arterial blood which, extracorporeally, had been in contact only with siliconized polyethylene in the cold. The strips were from large and small vessels from several sites in rabbit and dog. The contractions were reproducible and dose dependent. Threshold concentrations for contraction ranged from 2% to 30% depending on the source of the smooth muscle. In concentrations too low to produce contraction, plasma potentiated tension developed in response to stimulation by epinephrine, angiotensin, and KC1. The response of the strips to plasma was compared with their response to the several known vasoactive agents of plasma: epinephrine, norepinephrine, serotonin, angiotensin, vasopressin, bradykinin and histamine. Important differences were found. It is possible that in normal plasma there is an as yet undefined vasoactive component which in situ may play a role in the maintenance of vascular tone.
Adenosinetriphosphatase Activity of Cardiac Myosin
Authors: KATZ ARNOLD M. , REPKE DORIS I. , RUBIN BONNIE B.
Published: June 2012

Examination of the ATPase activities of rabbit cardiac, rabbit red skeletal and rabbit white skeletal muscle myosins has demonstrated the existence of two types of myosin. One type, characterized by the higher ATPase activity, is present in white skeletal muscle; the other is found in red skeletal and cardiac muscle. The differences between myosin preparations could not be attributed to varying degrees of actin contamination nor to changes occurring in the myosins during the preparative procedure. Chromatography of dog cardiac myosin on DEAE-cellulose showed a single component. No differences were observed between the cardiac myosins of the dog and rabbit.

Activation of the ATPase activity of cardiac myosin by Ca
++
was less than that of white skeletal myosin while the extent of inhibition by Mg
++
was similar for both. The stoichiometry of the interaction with actin of both cardiac and white skeletal myosins was similar but actin caused less activation of the cardiac myosin ATPase. Cardiac and white skeletal actins showed no differences in their abilities to activate myosin ATPase activity, which is in accord with previously documented similarities in the structures of these actins.

Comparison of the present findings with previously reported mechanical measurements made with intact muscles does not indicate that the intrinsic level of myosin ATPase activity determines the maximal tension developed during the active state. On the other hand, there may be a direct relationship between shortening velocity and myosin ATPase activity.
Laminar-Turbulent Transition Process in Pulsatile Flow
Authors: YELLIN EDWARD L.
Published: June 2012

A controlled ex-vivo study of a simple, sinusoidally oscillating flow in a rigid, constant-area, smooth tube, has produced significant insight into the laminar-turbulent transition phenomenon. The development of turbulence was studied by analyzing the dynamic characteristics of the transition process; i.e., the velocity, growth rate, and intermittency which describe the generation and propagation of turbulent slugs. A new concept, the relaxation time, has been introduced to interpret the effect of a periodic flow component superposed on a mean flow. Classical stability concepts, such as the point of inflection criterion and the Reynolds number, which have been derived from steady-flow analysis, are shown to require modification when applied to an oscillatory flow. Neither the mean nor the instantaneous Reynolds number is a sufficient criterion for determining the transition of laminar to turbulent flow in a pulsatile system. Other necessary criteria are: (1) a source of disturbances, (2) the relaxation time, and (3) the distance from the fluid under observation to the source of disturbance. The concept of relaxation time indicates that slowly oscillating flows of large amplitude tend to suppress or destroy turbulence downstream from sources of disturbance. Qualitative observations are presented which indicate that systolic acceleration may be laminar regardless of the large value of the instantaneous Reynolds number, while diastolic deceleration probably produces disturbed, but not turbulent or highly dissipative, flow.
Neural Stimulation of Release of Renin
Authors: BUNAG RUBEN D. , PAGE IRVINE H. , MCCUBBIN JAMES W.
Published: June 2012

Increased vasomotor discharge induced by bleeding caused renal release of renin in anesthetized dogs whether or not there was measurable change in either arterial pressure or total renal blood flow. Release of renin was prevented by ganglion blockade or local anesthesia of the renal nerves. Hemorrhage-induced release of renin occurred more consistently in dogs fed a low-sodium diet than in those fed a standard kennel diet. Stimulation of sympathetic vasomotor discharge by occlusion of the common carotid arteries, while renal perfusion pressure was kept constant, also caused release of renin, as did infusions of norepinephrine, tyramine, or DMPP. Isoproterenol, angiotensin, vasopressin, serotonin, or acetylcholine infused into the renal artery did not cause release of renin. It is concluded that neural stimuli are capable of causing release of renin in the absence of gross change in renal perfusion pressure or flow.
Body Surface Distribution of Equipotential Lines during Atrial Depolarization and Ventricular Repolarization
Authors: TACCARDI BRUNO
Published: June 2012

In 15 normal male human subjects and 6 dogs, 200 chest electrocardiograms were sequentially recorded. The distribution of equipotential lines on the thoracic surface was determined at 20 to 30 instants of time during atrial activation and ventricular recovery. In humans, the potential pattern is constantly dipolar, with one maximum and one minimum, during the P wave. The motion of the potential maximum and minimum on the chest surface appears to be related to the progress of the excitation through the auricular walls. At the end of the QRS interval, the simultaneous presence of activation and recovery potentials is generally observed, giving rise to several simultaneous maxima and minima. During the ST and T interval, recovery potentials show a dipolar distribution in normal subjects, but tripolar patterns are observed when the recovery process is altered in a circumscribed myocardial region. In dogs, multipolar distributions are frequently observed during the P wave, the ST segment and the T wave. During atrial activation and ventricular recovery, chest maps yield more information on the electrical activity of the heart (both normal and abnormal) than is offered by ordinary limb and precordial leads.
The Zero of Potential of the Electric Field Produced by the Heart Beat: The Problem with Reference to Homogeneous Volume Conductors
Authors: BAYLEY ROBERT H. , REYNOLDS ERNEST W. , KINARD CONRAD L. , HEAD JOHN F.
Published: June 2012

The acceptable zeros of the potential of the electrical fields produced by certain dipole distributions in homogeneous volume conductors is discussed. A bridge circuit is described by which a solution of the three-arm and the four-arm central terminals of Wilson may be solved for a zero of potential of the field produced by an arbitrary distribution of dipoles in a homogeneous volume conductor. An acceptable zero of potential for evaluation of the potentials in a locus on the "body" surface distant from the heart is described.
Development of Atherosclerosis in Dogs with Hypercholesterolemia and Chronic Hypertension
Authors: MOSES CAMPBELL
Published: June 2012

Hypercholesterolemia was induced in pure-bred dogs by cholesterol feeding and propylthiouracil or radioiodine. Hypertension induced by the injection of silica into the renal artery increased the severity of aortic atherosclerosis. Marked hypercholesterolemia increased the severity of aortic atherosclerosis even in normotensive dogs.
Artificial Maintenance of the Systemic Circulation without Participation of the Right Ventricle
Authors: JAMISON WILLIAM L. , GEMEINHARDT WILLIAM , ALAI JAHANGIR , BAILEY CHARLES P.
Published: June 2012

A pump of 50 cc. reservoir capacity, only 10 cm. in diameter, was placed in the systemic circuit between the left auricular appendage and the left common carotid artery in each of 10 dogs so that the systemic circulation was maintained by the pump during complete cardiac arrest resulting from experimentally produced ventricular fibrillation. All dogs recovered completely.
The Limits of Right Ventricular Compensation Following Acute Increase in Pulmonary Circulatory Resistance
Authors: GUYTON ARTHUR C. , LINDSEY ARTHUR W. , GILLULY JOHN J.
Published: June 2012

The ability of the right ventricle to compensate as the pulmonary artery is constricted appears to be determined by four major factors: (1) there occurs the well-known increased force of contraction as the right heart becomes distended; (2) the adequacy of the coronary circulation determines to a great extent the Degrees of pulmonary arterial constriction which can occur before failure occurs; (3) the circulatory reflexes apparently aid the compensation to a moderate extent; and (4) the greater the blood volume, the greater is the limit of compensation before right ventricular failure occurs.
The Thermoelastic Behavior of Isolated Aortic Strips of the Dog
Authors: LAWTON RICHARD W.
Published: June 2012

A detailed thermodynamic study of isolated strips of dog aorta is basic to the interpretation of the nonlinear and apparently rubber-like elastic behavior of such specimens. Experimental data indicate that the retractile force in isolated aortic strips of the dog is entropic. Volume changes with elongation in such strips are negligible. However, a large negative internal energy contribution to the total force is present at small elongations. Studies of aortic strips extracted with alkali suggest that the latter force arises from the elastic tissue itself.
Kinetic Constants of the Human Renin and Human Angiotensinogen Reaction
Authors: HAAS ERWIN , GOLDBLATT HARRY , Edwin C. Gipson , Lavera LeWis
Published: June 2012

The rate of formation of angiotensin was investigated for the reaction of angiotensinase-free human renin, at various states of purity, with angiotensinogen, in pooled, angiotensinase-free human serum. The velocity constant of this reaction and the Michaelis constant of the renin-substrate complex were determined. The concentration of angiotensinogen and of endogenous renin in human serum was also determined and, on the basis of these results, a procedure was designed for the indirect assay of human renin. This was carried out under a wide range of experimental conditions, for periods of incubation ranging from 10 min to 18 hours, for various concentrations of substrate, and for renin concentrations varying from 0.000025 to 0.20 unit/ml. The absence of angiotensinase made possible the prolonged incubation (18 hours) of a minute quantity of renin with a large amount of the renin substrate. The resultant formation of large amounts of angiotensin permitted its accurate assay in the dog.
Step Hypocapnia to Separate Arterial from Tissue Pco
2
in the Regulation of Cerebral Blood Flow
Authors: SEVERINGHAUS JOHN W. , LASSEN NIELS
Published: June 2012

The change in cerebral blood flow was determined after a step decrease in the Pco
2
of arterial blood from 40 to 25 mm Hg in awake man. Subjects monitored their own end-tidal Pco
2
(infrared analyzer) and adjusted their voluntary ventilation to produce the step change, which they maintained for at least 1 hour. Cerebral blood flow relative to control was determined from the arterial-jugular venous oxygen saturation differences. After the step change, arterial Pco
2
fell in less than 30 sec to a plateau, cerebral blood flow fell with a time constant (to 1/e) of 0.3 min to a plateau of 68% of control, while jugular venous Pco
2
fell with a time constant for the fast component of 3.5 min. Base excess rose 1.2 mEq/liter within 1 min and remained at that level. It is concluded that CO
2
affects cerebral blood flow by direct diffusion into arteriolar walls, rather than by its effect on brain tissue Pco
2
or pH. It is postulated that the pH of the extracellular fluid of arteriolar smooth muscle is the common controlled variable through which CO
2
, and possibly hypoxia and blood pressure, determine vascular tone.
Dependence of Wall Stress in the Human Thoracic Aorta on Age and Pressure
Authors: BADER HERMANN
Published: June 2012

The tangential wall stress and the tangential elasticity modulus at pressures from 0 to 200 mm Hg were calculated from pressure-volume diagrams of 27 human thoracic aortas aged 22 to 85 years. The relative volume increase of the aortas between 0 and 100 mm Hg decreased linearly from about 190% at age 20 to about 40% at age 85, whereas the elasticity modulus at 100 mm Hg increased linearly from 10 kg/cm
2
at age 20 to 42.5 kg/cm
2
at age 85. The decrease of the distensibility of the aortic wall with age was partly compensated by an increase of the internal volume of the aorta but at higher ages the distensibility was less than the theoretical values necessary for a proper buffering chamber activity. The tangential wall stress decreased linearly with age from about 2.5 kg/cm
2
at age 20 to about 1.2 kg/cm
2
at age 85. Since the pressoreceptors in the wall of the elastic vessels respond to the wall stress, this result means either that smooth muscles must increase the stress of the elastic fibers continuously, or the pressoreceptors must adapt their sensitivity throughout life to lower wall stress so that it will be kept constant. Weakness of the smooth muscles or a failure of the pressoreceptors to adapt themselves to lower stresses at higher ages may be the cause of essential hypertension.
Nature of Species Differences in the Medial Distribution of Aortic Vasa Vasorum in Mammals
Authors: WOLINSKY HARVEY , GLAGOV SEYMOUR
Published: June 2012

Thoracic aortic segments of 12 mammalian species were fixed while distended at normal physiological pressures after the vasa vasorum were filled by a perfusion mixture containing gelatin and carbon. Mammals whose aortas had 29 or fewer medial lamellar units had no demonstrable intramural vascular channels; those whose aortas had more than 29 medial lamellar units, had medial vasa. Aortas with medial vasa vasorum always had a subintimal medial zone devoid of vasa vasorum. In growing animals the width of this avascular zone increased with age; in adults, the width increased slightly with increasing species body weight. However, the number of lamellar units in the avascular zone was independent of both age and species and equal to 29.0 ± 2.5. All of the species with intramural aortic vasa vasorum as adults had 29 or more aortic medial lamellar units at birth; none of the species which had 29 or fewer lamellar units at birth had more than 29 lamellar units at maturity. In aortas with medial vasa vasorum, widening of the avascular zone during growth appeared to be due only to the uniform thickening of each of the approximately 29 lamellar units already present at birth; the vascularized outer zone widened both by enlargement of its lamellar units and the addition of new lamellar units. Species differences in medial distribution of vasa vasorum are due primarily to differences in thickness of the vascularized outer zone.