bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Vascular Endothelial Changes Associated with Increased Blood Velocity Gradients
Authors: FRY DONALD L.
Published: June 2012

The purpose of this study is to quantify the acute changes in endothelial histology that are associated with an induced increase in blood velocity. A nontraumatic intra-aortic device was designed to produce a rapid convergence of the aortic blood stream into a narrow channel along the ventral aspect of the thoracic aorta in dogs. The endothelial surface overlying this channel was exposed to a broad range of surface shearing stress by the accelerated blood flow. Techniques were developed to quantify the resulting distribution of shearing stress so that the stress to which the endothelial surface was exposed at every point along the channel could be determined. Special histologic techniques were developed using formalin fixation and gelatin embedding of the tissue so that endothelial cytology could be studied and criteria for normal cells established. Using these criteria, cell counts were done to establish the "normal" endothelial cell population density as a function of stress exposure. The stress corresponding to the mode of these cell density distribution curves was defined as the acute yield stress (τ

c

). The acute yield stress for endothelial cells was found to be 379±85 (
SD
) dynes/cm
2
. Exposure to stress in excess of this value for periods as short as one hour resulted in marked deterioration of the endothelial surface consisting of endothelial cytoplasmic swelling, cell deformation, cell disintegration, and finally dissolution and erosion of cell substance. The relationship of these events to cellular rheology and interfacial chemistry is discussed.
Autoregulatory Responses of Cat Mesenteric Arterioles Measured in Vivo
Authors: JOHNSON PAUL C.
Published: June 2012

The purpose of these studies was to measure changes in the diameter of arterioles as large-artery pressure was varied. Changes in diameter were measured with a flying spot microscope in blood vessels of the mesentery of anesthetized cats. Arterial pressure was reduced in a single step and held at a constant level until the change in the diameter was complete. In experiments on 34 arterioles, 10 vessels showed a simple decrease in diameter as pressure was reduced; 24 showed a biphasic response. In the latter group the vessel narrowed for the first 5 to 15 seconds, but after this time an autoregulatory response occurred and the vessel dilated. In 12 of these vessels the diameter became larger in hypotension than it had been at normal arterial pressure. When pressure was suddenly restored, the vessel dilated further but returned to the control size as the autoregulatory response occurred. Analysis of the findings suggests that conditions of stability are satisfied in various portions of the pressure range.
Sino-Atrial Reciprocation in the Isolated Rabbit Heart
Authors: HAN JAOK , MALOZZI ANNA Mae , MOE GORDON K.
Published: June 2012

Reciprocal beats between sinus node and atrium were studied in isolated rabbit heart tissue by microelectrode techniques. Early premature atrial responses which entered the sinus node frequently emerged to re-excite the atrium as "echoes." When the premature atrial beats discharged some but not all nodal areas, the atrial echoes, in turn, appeared to re-enter the sinus node. Repetitive reciprocation involving the sino-atrial circuit was occasionally observed. Anatomic and temporal patterns of excitation at multiple recording sites suggest that "entrance" block and slow conduction of premature impulses within the sinus node may explain the observed reciprocation. The results support the hypothesis that self-sustained reciprocation in a sino-atrial circuit might be responsible for some cases of paroxysmal atrial tachycardia.
Role of Histamine in Hypoxic Pulmonary Hypertension in the Rat
Authors: HAUGE ANTON , MELMON KENNETH L.
Published: June 2012

The present investigation was undertaken to see if any of the naturally occurring vasoactive substances was likely to act as a mediator for the pulmonary vasoconstrictor response to acute alveolar hypoxia. Rats were treated with agents that deplete local stores of vasoactive amines or inhibit their synthesis. Lungs from these animals were isolated, ventilated, and perfused with homologous blood at constant volume inflow. Their pressor responses to 2- to 3-minute periods of ventilation hypoxia (2% O
2
) were observed.

The histamine-releasing agent 48/80 or the histidine decarboxylase inhibitor NSD 1055, or both, depleted 73% of the histamine in the lung but had no consistent effect on the pressor responses to hypoxia. When 48/80 (0.2 to 1 mg) was given in vitro, histamine in the lung was reduced to 10% of normal, or less, and the pressor response to alveolar hypoxia was completely abolished.

Reserpine, guanethidine, or alpha-methyl-tyrosine reduced catecholamine stores in heart tissue (as an index of general tissue changes) by a maximum of 90% and reserpine decreased serotonin in the lung by 93% without inhibiting the hypoxic pressor responses. The findings strengthen the concept that histamine mediates the pressor response to acute alveolar hypoxia in the rat.
Contractile State of the Left Ventricle in Man
Authors: GAULT JAMES H. , ROSS JOHN , BRAUNWALD EUGENE
Published: June 2012

The contractile state of the left ventricle in man was analyzed by correlating left ventricular (LV) dimensional changes during contraction determined from cineangiograms, with simultaneous measurements of LV pressure. The mechanical characteristics of ventricular contraction were expressed quantitatively by deriving the extent and velocity of circumferential fiber shortening at the midwall and the time course of LV wall tension (stress); the instantaneous relations between tension, velocity, and length were then examined. In 6 patients without LV disease, wall tension became maximal soon after the onset of ejection, then declined rapidly; in 9 patients with LV disease, tension fell only slightly with continued ejection. The extent of shortening of the minor LV circumference was consistently less in patients with LV disease than in those without such disease. Velocity of circumferential fiber shortening throughout contraction ranged from 0.22 to 1.11 circumferences/sec in patients with LV disease and from 1.66 to 2.71 circumferences/sec in patients without LV disease, at comparable levels of wall tension (137 to 467 g/cm
2
, and 175 to 409 g/cm
2
, respectively). The initial rate of change of velocity of the circumferential fibers at the onset of ejection also was less than in the group without LV disease. The velocity of shortening of the contractile elements at maximum wall tension was 0.11 to 0.87 circumferences/sec in patients with LV disease and 1.46 to 2.04 circumferences/sec in patients without LV disease.
Effects of Hyperbaric Oxygen on Uteroplacental and Fetal Circulation
Authors: ASSALI N. S. , KIRSCHBAUM T. H. , DILTS P. V.
Published: June 2012

The effects of hyperbaric oxygen (at 3 atmospheres absolute) on uteroplacental and fetal circulations were studied in pregnant ewes near term. The ewe was given spinal anesthesia, the fetus was marsupialized to the abdominal walls to protect the umbilical circulation, and the fetal head was covered with a saline-filled glove to prevent breathing. During hyperbaric oxygenation, maternal arterial blood P
o
2
rose to 1,300 mm Hg while umbilical vein blood P
o
2
rose to 300 mm Hg; umbilical arterial Po
2
rose to only 50 mm Hg. Maternal and fetal arterial pressures did not change significantly, but uteroplacental and umbilical flows decreased slightly. Ductus arteriosus blood flows decreased strikingly when the oxygen tension of the pulmonary blood rose; net pulmonary blood flow increased markedly because of a decrease in pulmonary vascular resistance produced by oxygen. Ascending aortic flow increased, but effective fetal cardiac output (aortic plus ductus arteriosus flows) decreased. These studies indicate that the fetal pulmonary vascular bed is sensitive to oxygen in that it undergoes vasodilatation when the oxygen tension of the blood passing through it rises; the ductus arteriosus responds to the same stimulus by constricting. Hyperbaric oxygenation seems to establish a circulatory pattern in the fetus similar to that of the early neonatal period.
Electrophysiological Effects of Direct Current Countershock before and after Ouabain Sensitization and after Diphenylhydantoin Desensitization in the Dog
Authors: HELFANT RICHARD H. , SCHERLAG BENJAMIN J. , DAMATO ANTHONY M.
Published: June 2012

The effects of synchronized direct current countershock on ventricular automaticity, intraventricular conduction, and atrioventricular conduction were studied before and after ouabain administration and after diphenylhydantoin. At the level of electrical energy that induced ventricular arrhythmias, averaging 159 watt-seconds, countershock transiently increased ventricular automaticity and prolonged both intraventricular and atrioventricular conduction time. Immediately after ouabain-induced ventricular tachycardia returned to regular sinus rhythm, underlying ventricular automaticity and intraventricular and atrioventricular conduction times were increased. An average of 23 watt-seconds produced overt and persistent ventricular tachycardias due to enhanced automaticity or re-entry. Atrioventricular and intraventricular conduction times were also prolonged, and transient complete heart block occurred in two experiments. Diphenylhydantoin administration at this time depressed ventricular automaticity, caused a speeding of atrioventricular and intraventricular conduction times and increased the electrical energy necessary to produce ventricular tachycardia to 355 watt-seconds.
Mechanochemistry of Cardiac Muscle
Authors: CHANDLER BRIAN M. , SONNENBLICK EDMUND H. , POOL PETER E.
Published: June 2012

Norepinephrine increases myocardial contractility and myocardial oxygen consumption (MV
·
O
2
). It is not clear whether these phenomena are directly proportional or whether there is a disproportionate increase in MV
·
O
2
, signifying either uncoupling of oxidative phosphorylation or a direct increase in oxidative metabolism. Accordingly, the direct conversion of chemical energy to mechanical work was studied in control and norepinephrine-treated right ventricular papillary muscles from cats. Production of adenosine triphosphate (ATP) was inhibited by iodoacetic acid and N
2
. After resting or performing variable amounts of work, the muscles were instantly frozen, and the total amount of chemical energy (∼P = creatine phosphate + ATP) used was correlated with work performed and the number of contractions. There was no change in either the initial stores of energy or in the basal rate of energy utilization following treatment with norepinephrine. However, norepinephrine-treated muscles performing isometric work used 115% as much ∼P as control muscles in only 59% as many contractions and while performing only 87% as much work. Regression analysis of these data confirmed that norepinephrine-treated muscles used a greater amount of ∼P than do control muscles. Thus the increase in contractility induced by norepinephrine results in an increase in the amount of chemical energy released disproportionate to the amount of work performed, and the "oxygen wasting" effect of norepinephrine on heart muscle results from the increased utilization of energy associated with an increased contractile state.
Coronary Hemodynamic Effects of Increasing Ventricular Rate in the Unanesthetized Dog
Authors: PITT BERTRAM , GREGG DONALD E.
Published: June 2012

In five unanesthetized dogs with surgical heart block, increasing ventricular rate from 50--75 to 250--300 beats/min demonstrated an optimum ventricular rate of 130 to 185, above which aortic pressure and cardiac output fell. In contrast, coronary blood flow continued to rise to a ventricular rate of 250 to 300 beats/min. Stroke systolic coronary flow was well maintained over the entire range of ventricular rates studied, while stroke diastolic coronary flow fell with an increase of ventricular rate. A reactive hyperemic response following release of a 1- to 10-second coronary artery occlusion at a ventricular rate of 250 to 300 suggests that the fall in aortic pressure and cardiac output which occurred at these rates may not be due to an insufficiency of total coronary blood flow. Beta-receptor activity did not appear to play a significant role in the hemodynamic adjustment to increases in ventricular rate within the optimum range for cardiac output and aortic pressure from 52--77 to 115--156 beats/min.
Two-Dimensional in-Vitro Studies of Femoral Arterial Walls of the Dog
Authors: ATTINGER FRANÇoise M. L.
Published: June 2012

Analyses of the vascular system have characteristically been based on assumptions that the vessel wall is isotropic and that its properties and behavior can be linearized. To test the validity of these assumptions, excised arteries of dogs were submitted to stepwise strains tangentially and longitudinally during conditions of control, vasoconstriction, and inhibition of muscle metabolism. These strains were recorded simultaneously with the associated stresses, and the relations between stress and strain were studied during both dynamic-and steady-strain states. The vessels were anisotropic within most of the physiological ranges of tangential and longitudinal stress and strain. During control conditions the tangential modulus of elasticity was higher than the longitudinal; during vasoconstriction the situation was reversed for wall tensions corresponding to a blood pressure equal to or smaller than 190 mm Hg; however, above this value isotropic behavior prevailed. Vasoconstriction increased the non-linearity of the stress-strain relation, and decreased the modulus of elasticity of the arterial wall. The viscoelastic properties of the femoral artery were found to be different tangentially and longitudinally, as evidenced by a much larger amount of stress relaxation in the former direction than in the latter.
Flow in the Major Branches of the Left Coronary Artery during Experimental Coronary Insufficiency in the Unanesthetized Dog
Authors: KHOURI EDWARD M. , GREGG DONALD E. , LOWENSOHN HOWARD S.
Published: June 2012

The dynamic changes in the coronary circulation and the response to drugs were studied following experimentally induced coronary insufficiency. Flow measurements were made in the left circumflex and descending branches of the coronary artery, and in the ascending aorta; pressures were measured in the ascending aorta and the left ventricle. As the left circumflex coronary artery branch was gradually constricted, reactive hyperemia following a 10-second occlusion of that vessel decreased. When the Degrees of constriction became such that the control resting flow began to fall, there was no reactive hyperemia, and the contractility index of the heart decreased. Within less than 24 hours, flow in the descending branch of the left coronary artery rose, and the cardiac contractility index returned to control; peak flow rate in the descending branch during reactive hyperemia after a 10-second occlusion also increased. The response to isoproterenol, nitroglycerin, and dipyridamole was similar in direction before and after the partial reduction of flow in the left circumflex coronary artery branch. The response was less in the coronary vessel with partial occlusion; in the unimpeded descending coronary artery branch, the response increased progressively. These results are consistent with the development of collateral vessels.
Incidence of Arrhythmias in the Dog Following Transthoracic Ventricular Defibrillation with Unidirectional Rectangular Stimuli
Authors: STOECKLE HARRY , NELLIS STEPHEN H. , SCHUDER JOHN C.
Published: June 2012

The incidence of the various types of arrhythmia induced by defibrillation in anesthetized dogs that had had continous ventricular fibrillation for 30 seconds was studied as a function of the current strengh and the duration of the unidirectional rectangular pulse used to terminate the fibrillation. Shocks at 10, 20, 40, 80, and 100 amp with durations in the range of 80 µsec through 64 msec were used. At any given energy level the incidence of induced arrhythmias was much larger for the 40-, 80-, and 100-amp shocks than for the 10- and 20-amp shocks. At 10 and 20 amp, the incidence of induced arrhythmias increased with increasing energy content. Premature ventricular contractions were observed at nearly all levels of energy and current, in contrast to other types of arrhythmias that appear to be strongly related to energy content or current amplitude or both.
A Pressor Agent in Human Stable Plasma Protein Solutions
Authors: VANDONGEN ROBERT , GORDON RICHARD D.
Published: June 2012

A pressor material in human stable plasma protein solutions is described, and evidence that this material may be angiotensin II is presented. When six samples of stable plasma protein solution were assayed against standard angiotensin in the sensitive, ganglioplegic, nephrectomized rat anesthetized with urethane, the levels of pressor activity ranged from 320 to 830 ng/100 ml, with a mean of 552 ng/100 ml. The solution gives a pressor response similar to that of angiotensin II, is heat stable, dialyzable, and destroyed by trypsin and α-chymotrypsin, and reacts with the antibody in a radio-immunoassay for angiotensin II. It is present in sufficient concentration to have significant effects on blood pressure, renal handling of sodium, and aldosterone secretion when infused into patients at rates commonly employed.
Pulmonary Vasoconstriction Due to Nonocclusive Distention of Large Pulmonary Arteries in the Dog
Authors: HYMAN ALBERT L.
Published: June 2012

The pulmonary vascular changes caused by distention of the pulmonary artery with the lumen fixed were compared to those produced by occlusive arterial distention. In 13 urethane-anesthetized dogs, nonocclusive distention was produced by distention of a corrugated rubber cuff around a hollow metal cylinder affixed to the end of a cardiac catheter. In 10 other dogs, occlusive distention was produced by inflation of a standard balloon catheter. Pressures were measured in large and small pulmonary veins and in the left and right atria with transseptal techniques, and in the pulmonary and femoral arteries. Simultaneously, pulmonary blood volume and flow were measured with dyedilution techniques. Pulmonary arteriovenous shunting was studied with the hydrogen-electrode technique. Nonocclusive distention of a pulmonary artery greatly increased pulmonary arterial and venous pressure and decreased pulmonary blood volume without changing left atrial pressure or cardiac output. Pulmonary vascular resistances increased, and pulmonary arteriovenous shunting was detected. Occlusive distention of one pulmonary artery caused smaller increases in pressure in the pulmonary artery and vein of the unobstructed lung. Vascular resistances in the unobstructed lung decreased, while blood volume and flow in that lung doubled. Pulmonary arterial distention leads to active constriction of the pulmonary arteries and veins, but these responses may be obscured by the passive responses to increasing blood flow and volume.
Effects of High-Energy Phosphate Depletion and Repletion on the Dynamics and Electrocardiogram of Isolated Rat Hearts
Authors: SCHEUER JAMES , STEZOSKI S. WILLIAM
Published: June 2012

To explore the sequence of metabolic, mechanical, and electrocardiographic (ECG) events during myocardial anoxia, isolated rat hearts were paced from the atrium. Anoxic and recovery periods were studied. Adenosine triphosphate (ATP) and creatine phosphate (CP) declined to 50% of control during the first minute and remained at that level for the 5-minute anoxic period. ATP and CP returned to control values after 10 and 20 seconds of recovery. Lactate and potassium efflux from the myocardium closely followed the highenergy phosphate changes. During anoxia, left ventricular systolic pressure increased initially, then fell below the control level after 2 minutes, and recovered within 20 seconds of reoxygenation. In catecholamine-depleted hearts, it fell immediately with anoxia, and recovery was incomplete. The conduction time for the pacing stimulus to reach the ventricle increased with anoxia and decreased with reoxygenation. S-T alterations in the ECG also lagged behind high-energy phosphate reduction and recovery.

The study demonstrates that in the isolated heart, ECG evidence of myocardial hypoxia may be absent when high-energy phosphate levels in the myocardium are very low. Mechanical changes are more closely related temporally to high-energy phosphate alterations than are ECG changes. The release of endogenous catecholamines is important to maintain mechanical function in the hypoxic heart.
The Contribution of Blood Momentum to Left Ventricular Ejection in the Dog
Authors: NOBLE MARK I. M.
Published: June 2012

In five conscious dogs and two anesthetized dogs, the pressure gradient between the left ventricle and the ascending aorta was measured with high fidelity micromanometers. Left ventricular pressure exceeded aortic pressure in the first 30 to 50% of the ejection period. Aortic pressure exceeded left ventricular pressure during the remainder of the ejection period. The magnitude of these differences varied from 5 to 20 mm Hg. This finding in late systole implies that at this time blood is flowing out of the ventricle under its own momentum and that the aorta is a pressure source for the ventricle. The ascending aorta was suddenly occluded in five dogs to verify this hypothesis. When occlusion occurred in the last third of the ejection period, there was an abrupt fall of left ventricular pressure, apparently confirming the momentum hypothesis.
Effects of Low and High Concentrations of Potassium on the Simultaneously Recorded Purkinje and Ventricular Action Potentials of the Perfused Pig Moderator Band
Authors: GETTES LEONARD , SURAWICZ BORYS
Published: June 2012

The use of the perfused pig moderator band has allowed us to study the rapid simultaneous changes in Purkinje and ventricular action potentials induced by perfusing solutions of high (10 to 12 m
M
) and low (0.6 to 0.8 m
M
) K concentrations. High K shortened the plateau more in Purkinje fibers than in ventricular fibers and decreased the difference between the action potential durations of the two fiber types. Low K prolonged the plateau in Purkinje fibers but shortened it in ventricular fibers and increased the difference between the action potential durations. Low K initially hyperpolarized both Purkinje and ventricular fibers. However, the resting potential of the Purkinje fiber subsequently decreased as phase-4 depolarization increased. The decreased maximum repolarization potential associated with low K-induced pacemaker activity was time rather than voltage dependent. When the perfusate was changed from low K to control (K = 4.8 m
M
), phase-4 depolarization was rapidly suppressed and the action potential of the Purkinje fiber was shortened to less than that produced by high K, and then changes in amplitude of the resting and action potentials occurred. Our observations help to explain some of the effects of low and high K on rhythm and conduction.
Abnormal Cardiac Norepinephrine Storage in Isoproterenol-Treated Rats
Authors: MUELLER ROBERT A. , AXELROD JULIUS
Published: June 2012

Repeated administration of large doses of isoproterenol to rats produced myocardial enlargement and a fall in blood pressure. A defect in storage of norepinephrine (NE) was manifested by a decrease in endogenous NE, unimpaired uptake of
3
H-NE, and an accelerated rate of loss of accumulated
3
H-NE. This accelerated loss of
3
H-NE was characterized by a more rapid disappearance of
3
H-NE from the granular or microsomal than from the supernatant NE fraction. The increased rate of loss of
3
H-NE could be reversed by treatment with a ganglionic blocking agent, chlorisondamine, by salt restriction and mercurial diuresis, and by withholding isoproterenol treatment for 7 days. The NE storage defect resembled that previously described in the hearts of rats made hypertensive by administration of desoxycorticosterone and NaCl. It is possible that the NE storage defect in the hearts of isoproterenol-treated rats is the result of a combination of changes in sympathetic nervous activity and altered neuronal electrolytes.
Effects of Adrenal Steroid Withdrawal on Chronic Renovascular Hypertension in Adrenalectomized Sheep
Authors: BLAIR-WEST J. R. , COGHLAN J. P. , DENTON D. A. , FUNDER J. W. , SCOGGINS B. A. , WRIGHT R. D.
Published: June 2012

Adrenalectomized sheep with a single kidney were maintained chronically hypertensive after renal arterial constriction on a maintenance dosage of desoxycorticosterone acetate and cortisone acetate. This level of steroid support is totally without pressor effects in adrenalectomized animals with normal kidneys. Blood pressure was monitored after steroid withdrawal with (1) no replacement of Na
+
loss, (2) intravenous replacement of Na
+
loss, (3) withdrawal of one steroid alone. When cortisone alone was withdrawn, the plasma [Na
+
] and [K
+
] remained within normal limits, no natriuresis occurred, and the blood pressure remained elevated. When both steroids, or DOCA alone, were withdrawn, a profound natriuresis and alteration in plasma ionic concentrations occurred; the blood pressure, however, remained persistently elevated above the values obtained before renal arterial constriction despite clinical and biochemical evidence of adrenoprival status. This pattern of blood pressure response compared with that following release of the constriction is interpreted as evidence against a causative role for the adrenal cortex in the mechanism of renovascular hypertension.
Interstitial Pressure of the Lung
Authors: MELLINS ROBERT B. , LEVINE O. ROBERT , SKALAK RICHARD , FISHMAN ALFRED P.
Published: June 2012

The effects of alveolar and pleural pressures on pulmonary interstitial pressure were studied in 36 anesthetized dogs by application of Starling's law of transcapillary exchange. Fluid accumulation in the lung was produced by increasing left atrial pressure to levels always higher than alveolar pressure and by hemodilution with saline. Using a lung divider, a difference in alveolar pressure of from 5 to 14 mm Hg was achieved between the two sides in 24 dogs. Increased alveolar pressure did not reduce the rate of fluid accumulation, indicating its lack of effect on interstitial pressure. A relationship between the rate of fluid accumulation and the forces in the Starling equation was demonstrated when pleural pressure was included as an index of interstitial pressure. The rate of fluid accumulation increased markedly when interstitial pressure exceeded atmospheric. Fluid accumulation was considerably less in lobes statically inflated with plasma than in contralateral lobes ventilated with air (6 dogs); this difference could not be attributed to static inflation as opposed to ventilation (6 dogs). These findings suggest that surface tension opposes the transmission of alveolar pressure to the interstitial space. The interstitial pressure, as measured by application of Starling's law, acts on the small vessels within the alveolar-capillary membrane.
Application of the Theory of Heat Exchangers to the Transfer of Inert Materials in Placentas
Authors: FABER J. JOB
Published: June 2012

Calculations were made on a variety of models to determine to what extent placental structure (vascular geometry and permeability) and placental function (rate and evenness of distribution of fetal and maternal blood flows, and presence of nonexchanging shunts) affect the rate of diffusional exchange across the placental barrier. The results of the calculations are given in the form of a graphical relationship between three dimensionless variables defined in the text. It is shown that experimentally measured transfers can also be represented in this form and thus compared to transfers that are theoretically predicted. The results indicate that biologically probable degrees of regional variation in permeability are harmless, but that this is not true of uneven distributions of maternal-fetal blood flow ratios. They further show that the relative magnitudes of blood flows through nonexchanging shunts can be found by extrapolation of experimental data obtained with substances whose transfers are entirely flow limited, but that the use of such substances cannot help to separate the effects on placental exchange due to vascular geometry from those due to uneven distribution of flow ratios. Methods are indicated with which the value of the placental permeability can be assessed experimentally under various conditions.
Left Ventricular Filling and Diastolic Pressure-Volume Relations in the Conscious Dog
Authors: NOBLE MARK I. M. , MILNE ERIC N. C. , GOERKE R. JON , CARLSSON ERIK , DOMENECH RAUL J. , SAUNDERS KENNETH B. , HOFFMAN JULIEN I. E.
Published: June 2012

In 7 conscious dogs, left ventricular diastolic volume (V) was estimated by taking biplane cineradiographs with the left ventricular cavity previously outlined by permanent radiopaque markers. Left ventricular pressure (P) was measured with an implanted miniature transducer. There were two rapid filling periods during early and late diastole; little filling occurred during the middle third of diastole (diastasis). The diastolic pressure-volume relationship was approximately exponential and was fitted by the equation P=-
a+be

c
v

, where,
a, b
, and
c
are positive constants; the relationship appeared to be determined principally by the elastic properties. The effects of infusions of saline, isoproterenol, calcium gluconate, and methoxamine suggested that viscous and inertial properties are also important determinants of diastolic left ventricular mechanics. No significant series viscosity was observed. Plastic properties were not detected. The elastic properties were not affected by agents having a positive inotropic effect. End-diastolic pressure often differed from that predicted by the exponential equation above, suggesting that it is not a reliable index of enddiastolic volume and left ventricular compliance.
Effect of Changes in Heart Rate on Left Ventricular Performance in Conscious Dogs
Authors: NOBLE MARK I. M. , WYLER JANE , MILNE ERIC N. C. , TRENCHARD DIANA , GUZ ABRAHAM
Published: June 2012

An increase in heart rate produced in 12 conscious dogs by right atrial pacing resulted in a fall of end-diastolic volume, stroke volume, stroke work and end-diastolic pressure. Stroke power and the maximum rate of increase of left ventricular pressure (LV dP/dt max) were affected only slightly. Sudden large changes of rate produced transient changes in LV dP/dt max typical of the positive and negative inotropic effects of activation, but steady-state LV dP/dt max was not affected; these effects persisted after autonomic blockade with propranolol and atropine. Postural changes produced no change in LV dP/dt max even after autonomic blockade. We conclude that in this preparation, the interval-strength relationship has a plateau at the physiologic range of heart rate, i.e., myocardial contractility is unaffected by change in heart rate over the range 90 to 190 beats/min.
Cutaneous Venoconstrictor Response to Local Cooling in the Dog
Authors: WEBB-PEPLOE MICHAEL M.
Published: June 2012

Studies were performed in dogs to determine if inhibition of neuronal reuptake of norepinephrine was the cause of the enhanced response to sympathetic nerve impulses seen in the cutaneous veins when the temperature of the blood perfusing them was decreased. Changes in driving pressure of the saphenous vein perfused with blood at constant flow were used to measure venomotor responses. The increases in venoconstrictor response to norepinephrine infusion caused by cooling the perfusate were similar in both hindlegs, one subjected to acute and the other to chronic sympathectomy. Blocking the reentry of norepinephrine into the sympathetic nerve endings by treating the vein with cocaine did not affect the augmentation by local cooling of the constrictor response to norepinephrine or electric stimulation of the lumbar sympathetic chain. The venoconstrictor responses to norepinephrine, epinephrine, 5-hydroxytryptamine, and molar potassium chloride were all augmented by local cooling. The results suggest that the sensitizing effect of cold on the smooth muscle of the veins cannot be explained by inhibition of norepinephrine re-uptake by the nerve terminals.
Binding Characteristics of Myosin and F-Actin from Dog Hearts
Authors: CONWOY GENE , HEAZLITT ROBERT , ROBERTS JOE L. , STEWART LEROY
Published: June 2012

We used light scattering and ultracentrifugation to study the binding ratio of myosin and actin from normal and failing dog hearts and to determine the effect of temperature and adenosine triphosphate (ATP) on the binding. For comparison, similar studies were done on myosin and actin from rabbit skeletal muscle.

We found a higher combining ratio, by weight, for cardiac myosin and actin (4.8 : 1) than for skeletal myosin and actin (4.4 : 1). The dissociation constants were similar at 24°C for cardiac and skeletal proteins. But at 10°C, the dissociation constant was greater for cardiac proteins, and the difference appeared more pronounced when phosphate was used to buffer the solutions.

The dissociation constant at 10°C was greater for myosin and actin from failing dog hearts.

ATP caused dissociation of cardiac and skeletal F-acto-heavy meromyosin and F-actomyosin. There was evidence that the binding of cardiac proteins may not be as tight as that of skeletal muscle proteins.
Dynamic Characteristics of the Cardiovascular Autonomic Effects during Severe Arterial Hypoxia in the Unanesthetized Rabbit
Authors: KORNER PAUL I. , UTHER JOHN B.
Published: June 2012

The reflex autonomic effects due to inhalation of low concentrations of oxygen (Pao
2
30 mm Hg) were assessed in unanesthetized rabbits from the differences in responses between groups of normal and autonomically "deefferented" rabbits and those with selective effector block. Changes due to autonomic effects were estimated for heart rate, total and regional (portal, renal, muscle, and cutaneous) peripheral resistance, and the rate of epinephrine secretion. The autonomic effects could be described by an early component having a time course similar to the initial vagal effects, where the maximum change occurred soon after the start of hypoxia and then declined to 37% of this value in 5 minutes, and a late component similar to the neural effects in muscle, starting 5 minutes after the start of hypoxia and rising slowly to 63% of the maximum in 15 minutes. Four autonomic effector patterns involving different combinations of early and late components were distinguished: (1) vasoconstriction in the portal and renal beds followed the time course of the sum of early and late components; (2) inhibition of cutaneous constrictor tone was the mirror image of the above response; (3) the biphasic sympathoadrenal effect on heart rate was the sum of a negative early and positive late component; (4) the neural constrictor effect in muscle and the rate of epinephrine secretion had only a late component. The early effects resulted in reduction in cardiac output and major redistribution of peripheral blood flow, probably due to chemoreceptor stimulation. During the late phase, cardiac output rose and blood flow was redistributed further, probably mainly through baroreceptor mechanisms.
Effect of Cardiotonic Lactones on Calcium Metabolism of Dog Cardiac Microsomes
Authors: ENTMAN MARK L. , COOK JOSEPH W. , BRESSLER RUBIN
Published: June 2012

The effects of several lactones were studied in a microsomal fraction of dog myocardium thought to be sarcoplasmic reticulum. The lactones increased the steady-state accumulation and turnover of calcium only in the presence of ATP, and augmented the calcium-stimulated ATPase activity. When the effective concentrations of the lactones were exceeded, there were no further alterations in calcium accumulation or turnover. A correlation between the capacity of these lactones to increase calcium accumulation and turnover and their relative cardiotonic activity, as reported in the literature, was noted. The potency of the lactones in relation to calcium metabolism in the microsomes is influenced by ring saturation, position of the double bond, and presence of a steroid ring system to the lactone moiety.
Effect of Hematocrit Value upon Electromagnetic Flowmeter Sensitivity
Authors: DENNIS JENNIFER , WYATT D. G.
Published: June 2012

An electromagnetic flowmeter system that has an accuracy of 0.1% and is insensitive to fluid conductivity was used to study the sensitivity to steady flow of a 6-mm cannular transducer. All measurements were carried out at 37°C. Sensitivity decreased with increasing hematocrit value whether flow was laminar or otherwise. With laminar flow and a given hematocrit value, the sensitivity also decreased with increasing flow rate. Sensitivity started to rise when increasing flow rate caused departure from the laminar regime. At the lowest flow used in the laminar regime (250 ml/min), the sensitivity fell 4% when the hematocrit value was changed from 0 to 66% at 39.5% the reduction in sensitivity was 2%. With laminar flow at hematocrit 39.5% the sensitivity fell 1% as flow increased from 250 to 1500 ml/min. At hematocrit 29.5% the sensitivity rose 1.2% when the flow regime changed from laminar to turbulent. The changes may be explained in terms of a radial distribution of cells, of which a cell-free boundary layer is a particular example. Theoretical calculations show that the thickness of an apparent cell-free boundary layer must be tens of microns to explain the observations with laminar flow and that the apparent thickness is greatly reduced with onset of turbulence. A possible mechanism is described by which the results could be explained in terms of cell orientation.
Biphasic Stimulation of Aldosterone Secretion during Hemorrhage in Dogs
Authors: FABRE LOUIS F. , FARMER ROBERT W. , DAVIS H. WINSTON , MCBEE GEORGE , FARRELL GORDON
Published: June 2012

The increase of aldosterone secretion in response to hemorrhage has been reevaluated with the aid of a newly developed micromethod using gas-liquid chromatography. Pentobarbital-anesthetized large male dogs were slowly exsanguinated through the lumboadrenal vein while sequential 15-minute samples of adrenal venous effluent were collected. Mean arterial blood pressure and blood loss were monitored. The response to hemorrhage was found to be biphasic; a significant increase in aldosterone secretion occurred before blood pressure changed significantly, the secretory rates then fell toward control, and rose again as the blood pressure fell to shock levels. Statistical evaluation of the data confirmed the quartic nature of the response and indicated a best-fit equation of y = 169.14x - 800.22x
2
+ 1258.46x
3
- 619.24x
4
.

These results demonstrate that control of aldosterone secretion is dependent on complex functions of blood volume and blood pressure. Volume receptor mechanisms as well as pressure receptor mechanisms would seem to be involved. Any investigation of the aldosterone response to hemorrhage, to be valid, must take these complex relationships into consideration.
Effect of Ouabain on the Energy Output of Rabbit Cardiac Muscle
Authors: GIBBS C. L. , GIBSON W. R.
Published: June 2012

The effect of ouabain, 0.3 µg/ml, on the energy output of rabbit papillary muscles has been examined by a myothermic technique. The experiments were conducted at two temperature ranges, 19.2° to 22.8°C and 29.0° to 32.2°C, and both isometric and afterloaded isotonic contractions were studied. Temperature differences alone caused pronounced physiological changes, the higher temperature being associated with lower tension-independent heat and markedly higher active efficiency, external work /(external work + active heat production). The heat versus tension curve was rectilinear at higher temperatures but showed upward curvature at lower temperatures. At 19.2° to 22.8°C, ouabain increased the tension-independent heat by 23%, maximum tension development by 23%, and mean work output by 39%. Ouabain did not significantly alter the slope of the heat versus tension curve and increased mean efficiency only slightly. At 29° to 32.2°C, ouabain did not cause any significant change in the slope of the heat versus tension curve or in mean muscle efficiency. Ouabain produced significant increases in maximum tension development, mean work output, and the tension-independent heat. The effects of ouabain at the higher temperature were examined at two different calcium levels, 2.5 and 1.25 mM. In the isometric studies the effects of ouabain were independent of the calcium level, and the calcium level itself had no significant effect on the heat-tension relationship. In the isotonic studies, ouabain increased work output but more so at the 2.5 mM calcium level. Ouabain did not affect mechanical efficiency at either calcium level but muscle efficiency was higher at the 2.5 mM calcium level. It is concluded that any effects of the cardiac glycosides on energy expenditure are consequences of their inotropic actions and do not represent changes in the energy cost of contraction.
Modification by Acetylcholine of the Response of Rat Mesenteric Arteries to Sympathetic Stimulation
Authors: MALIK KAFAIT U. , LING GEORGE M.
Published: June 2012

The aim of this study was to determine the effect of varying concentrations of acetylcholine on the vasoconstriction of the perfused mesenteric arteries of the rat caused by stimulation of their sympathetic postganglionic nerves. Perfusion was carried out with a peristaltic pump, and the constriction caused by stimulation was measured by the rise of pressure in the cannula tied in the artery. Two effects were found. At rates of stimulation between 2 and 8/sec, acetylcholine added to the perfusion fluid in very low concentrations (50 pg/ml) caused an increase in the vasoconstriction. An increase was also caused by adding a concentration of 2 ng/ml for 15 seconds. If, however, this or a greater concentration was added for a longer time, it had the opposite effect and the vasoconstriction was greatly reduced or blocked. This reduction or block was not due in the main to a reduction or block of the vasoconstrictor action of norepinephrine. Block of response to stimulation was also produced by guanethidine. The block produced by acetylcholine resembled the block produced by guanethidine in two respects. The block was removed by raising the calcium concentration, and it was also removed by adding
d
-amphetamine to the perfusion fluid. The block produced by a given concentration of acetylcholine was abolished by a much higher concentration of atropine or hyoscine.
Effects of Hypoxia and Metabolic Inhibitors on the Intrinsic Heart Rate and Myocardial Contractility in Dogs
Authors: JOSE ANTHONY D. , STITT FRANK
Published: June 2012

Previous studies have shown that after autonomic blockade by propranolol and atropine, the intrinsic rate and contractile function of the heart were related in patients with myocardial failure. In this study the intrinsic rate and ventricular contractile force were measured in dogs during acute heart failure produced by agents which impair myocardial energy syntinesis, to see whether these conditions reproduced the relationship found in naturally occurring myocardial disease in man. Anesthetized dogs, after propranolol and atropine, were either ventilated with 6% oxygen or given sodium cyanide, parachloromercuribenzoate, or dinitrophenol by intravenous infusion. Hypoxia and cyanide initially increased and then depressed both rate and contraction. Parachloromercuribenzoate depressed both. Dinitrophenol depressed only contraction. During hypoxia, cyanide, and parachloromercuribenzoate the percent changes in contractile force and intrinsic rate were linearly related (r=0.87) with slopes of 3.2, 2.7, and 3.3, respectively. These results together with previous data during pentobarbital and aminophylline were consistent with a single linear relationship between rate and contractility (r=0.89, slope 3.2). This resembled closely the relationship found previously in man. It is suggested that in both situations, this relationship may be determined by a dependence of rate and contractility on similar limited sources of energy.
Function of the In-Situ Papillary Muscle in the Canine Left Ventricle
Authors: CRONIN ROBERT , ARMOUR J. A. , RANDALL WALTER C.
Published: June 2012

From strain gauge arches applied directly to the longitudinal surface of the papillary muscle of the canine left ventricle, its force of contraction was recorded simultaneously with that on an epicardial segment of the ventricle immediately overlying it. Left ventricular and atrial pressures, as well as ECG and local electrograms were also recorded in a closed-heart, open-chest preparation. Active participation of the papillary muscle in the contractile processes of the whole heart is indicated, and under positive inotropic drive (stellate stimulation, administration of isoproterenol, norepinephrine) the force of contraction of this muscle is greatly augmented. During volume loading resulting from afterloading procedures (central vagus stimulation, methoxamine, aortic clamping) the papillary muscle participates in augmenting the contractile force, but in lesser proportion than when elicited by a direct positive inotropic procedure. The increase in contractile force during afterload was related to passive changes in length-tension relationships. Direct vagal innervation of the papillary muscle is indicated by distinct inhibition in contractile force during electrical excitation of the peripheral end of the cut vagosympathetic trunk, both in the paced and unpaced preparation.
Effects of Saline Loading on the Renin, Erythropoietin, and Blood Pressure Responses to Canine Renal Allotransplantation
Authors: ABBRECHT PETER H. , VANDER ARTHUR J. , TURCOTTE JEREMIAH G.
Published: June 2012

Serial determinations of plasma erythropoietin and renin activities and mean arterial blood pressure were done in five dogs before and after renal allotransplantation. Throughout the experiment, the animals were given 154 mEq of NaCl per day, starting 1 week before transplantation. No immunosuppressive therapy was given. Onset of immunological rejection was determined by daily measurement of endogenous creatinine clearance. Arterial pressure and plasma erythropoietin concentration increased markedly at the time of rejection, with the curves for the two variables closely paralleling each odier in all animals. Serial determinations of plasma volume done in two of the dogs did not show any significant change at the time when hypertension appeared. Plasma renin activities remained very low throughout the experiments, indicating that even with the vascular lesions of rejection renin release is still subject to normal control mechanisms. It is concluded that elevated plasma renin activity is not an essential causal factor of the hypertension which occurs with renal allograft rejection. Since it is possible to suppress renin release without substantially inhibiting erythropoietin release, different stimuli appear to cause release of these substances.
Biochemical Correlates of Cardiac Hypertrophy: III. CHANGES IN DNA CONTENT; THE RELATIVE CONTRIBUTIONS OF POLYPLOIDY AND MITOTIC ACTIVITY
Authors: Grove David , Nair K. G. , Zak Radovan
Published: June 2012

DNA concentration in the left ventricle of 3-month-old rats 3 to 12 days after aortic constriction was similar to the values obtained in sham-operated litter mates (1.38 ± 0.03 µg/mg wet weight). The total DNA content of the heart was thus increased proportionally to its enlargement. In chronic hypertrophy (2 to 4 months after aortic constriction), the DNA content was increased to a significantly less extent than in short-term hypertrophy. The percentage of polyploid nuclei in 12- to 13-week-old rats increased 1 to 3 weeks after aortic constriction from a normal value of 1.8% to 4.2%. In 17- to 18-week-old rats, polyploidy was present in 3.9% of the nuclei 10 days after banding as compared with 1.6% in normal rats. Mitotic figures were localized almost exclusively outside muscle cells. Mitotic indices in hypertrophied hearts were ten times higher than in controls during the first 3 weeks after aortic constriction.