bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions of Quinidine and Potassium on Atrioventricular Transmission
Authors: WATANABE YOSHIO , DREIFUS LEONARD S.
Published: June 2012

The effects of quinidine and its interactions with potassium (K) on atrio-ventricular (A-V) conduction were studied in isolated, perfused rabbit hearts, utilizing microelectrode techniques. Quinidine gluconate (10 mg/liter) was added to perfusion fluid containing either normal [K
+
] (4.5 mEq/liter), low [K
+
] (1.5 mEq/liter), or high [K
+
] (7.5 mEq/liter). The following observations were made: (A) The marked prolongation of A-V conduction time produced by quinidine was antagonized by low K
+
and enhanced by high K
+
concentration. (B) Quinidine or high K
+
concentration prolonged the A-V interval by slowing intra-atrial and His-Purkinje-ventricular conduction. (C) Low K
+
concentration depressed conduction in the N region of the A-V node. (D) Lowering K
+
concentration in the presence of quinidine shortened the A-V interval by enhancing His-Purkinje-ventricular conduction. (E) Quinidine and high K
+
concentration increased the action potential amplitude in the nodal and the node-His regions of the A-V node while low K
+
concentration showed opposite effects. Hence, different regions of the A-V conducting system were selectively influenced by these agents. A-V conduction in the presence of low K
+
and quinidine depends upon the net results of their antagonism within individual fiber types. The importance of these interrelationships in pharmacologic approach to A-V conduction disturbances is stressed.
A Study of the Mechanisms Involved in the Pulmonary Arterial Pressor Response to Hypoxia
Authors: BERGOFSKY EDWARD H. , HOLTZMAN SEYMOUR
Published: June 2012

The mechanisms underlying the pulmonary arterial pressor response to hypoxia have been investigated by studying specimens of pulmonary and systemic vascular smooth muscle and the isolated pulmonary and systemic circulations. Hypoxia caused a unique and reversible loss of potassium and gain in sodium by pulmonary arterial smooth muscle that did not occur in pulmonary veins or systemic arteries. These changes in electrolyte concentrations were calculated by the Nernst equation to be associated with depolarization of the smooth muscle cell of the pulmonary artery. Moreover, artificial hyperpolarization and depolarization in the isolated perfused pulmonary circulation were attended by blunting and accentuation, respectively, of the pulmonary arterial pressor response to hypoxia.

Such data suggest that one of the actions of hypoxia on the pulmonary circulation involves a depolarization of the muscle cell so that it is closer to its excitatory threshold and thereby more readily able to diminish the cross-sectional area of the pulmonary vascular bed.
Plasma Renin Activity and Renin-Substrate Concentration in Patients with Liver Disease
Authors: AYERS CARLOS R.
Published: June 2012

Peripheral venous renin activity was determined by the method of Boucher in 15 patients with cirrhosis of the liver and ascites who were on an unrestricted sodium intake. Positive sodium balance was present in all subjects. Marked elevation of mean plasma renin activity (43 ng angiotensin II/min per liter, SD±38) was present. The mean plasma renin activity in 16 normal ambulatory subjects on an unrestricted sodium intake was 10.7 ng (SD±4.9) of angiotensin II/min per liter. The difference was highly significant,
P
< 0.01. A zero-order enzyme reaction occurred in all but 1 patient; the first-order enzyme reaction in this 1 patient suggests a low renin-substrate concentration in liver disease. The renin-substrate concentration was determined in 18 patients with liver disease (13 with cirrhosis and 5 with hepatitis) and in 10 normal subjects. The renin substrate was expressed in equivalents of angiotensin II formed/100 ml plasma. The mean renin substrate in 13 patients with cirrhosis and ascites was 17,193 ng (SD±6556); the normal mean renin substrate was 34,385 ng (SD ± 5,679),
P
< 0.01. The lowest renin substrate concentration was seen in 2 patients with severe hepatitis.
Hepatic Inactivation of Renin
Authors: HEACOX ROBERT , HARVEY ALICE M. , VANDER ARTHUR J.
Published: June 2012

Renin activities were measured in plasma from an artery and from the hepatic, portal, and renal veins of anesthetized dogs. A significant arterial-hepatic venous renin difference was observed during control periods and after elevation of arterial renin by stimulation of endogenous renin secretion (induced by acute salt depletion) or by infusion of exogenous renin. There was good quantitative agreement between the calculated rates of renin infusion and hepatic renin clearance. No significant arterial-portal venous renin difference was observed. Infusion of exogenous renin decreased the usual renal venous-arterial renin difference; slight net renal inactivation of renin was observed in only 2 of 12 periods. We conclude that the liver is the major site of renin inactivation.
Quantitative Aspects of Dog Cardiac Microsomal Calcium Binding and Calcium Uptake
Authors: KATZ ARNOLD M. , REPKE DORIS I.
Published: June 2012

Crude microsomes prepared from dog ventricular myocardium by differential centrifugation bound 0.029 µmole of Ca/mg of microsomal protein in the absence of oxalate, and accumulated 1.92 µmole Ca/mg in the presence of oxalate. Purified cardiac microsomes, obtained by sucrose density-gradient ultracentrifugation of the crude microsomes, bound 0.026 µmole Ca/mg and accumulated 2.32 µmole Ca/mg. The total Ca-binding capacity of the myocardium, based on the yields and Ca-binding activities of the crude microsomes, was 0.050 µmole/g wet weight of the ventricle. This value is very nearly equal to the amount of Ca believed to be removed from the actomyosin during relaxation, suggesting that myocardial relaxation may be effected by Ca binding to the sarcoplasmic reticulum. The binding constant for Ca binding to cardiac microsomes is approximately 10
5
M
-1
. Purified cardiac microsomes lowered free Ca from 10
-5
M to approximately 10
-7
M in the presence of oxalate, but Ca uptake proceeded much less rapidly than did Ca binding. Calcium uptake followed first order kinetics. A typical rate constant was 0.24 sec
-1
mg microsomal protein
-1
, giving a rate constant of 0.047 sec
-1
, for the initial uptake from a solution of 10
-5
M CaCl
2
by 1 g of heart based on the yields of purified microsomes. This rate is significantly lower than that of relaxation in the intact ventricle, and remains so even if the higher yields of crude microsomes are used in the calculation.
Myocardial Infarction Following Coronary Ligation in Dogs
Authors: HOOD WILLIAM B. , MCCARTHY BRIAN , LOWN BERNARD
Published: June 2012

In the subacute phase of myocardial infarction following coronary ligation in dogs, a relationship was noted between the extent of infarction and the degree of elevation of left ventricular end-diastolic pressure. Left ventricular filling pressure was consistently increased when 25% or more of the left ventricle was infarcted. Isoproterenol infusion resulted in enhanced left ventricular function in both control and infarcted dogs, but the response was clearly weakened in those animals in which more than 20% of the left ventricle was infarcted. Acetylstrophanthidin caused no improvement in left ventricular function in infarcted dogs as judged by the relationship between filling pressure and cardiac output. The peak rate of rise of left ventricular pressure did increase in animals with infarcts, but was less than that in controls. Animals with infarcts had a lowered threshold for production of ventricular tachycardia by acetylstrophanthidin. These results in dogs suggest the need for further assessment of the role of digitalis in the treatment of heart failure following acute myocardial infarction.
Fine Structure of Myocardial Mitochondria in Rats after Exercise for One-Half to Two Hours
Authors: LAGUENS RUBÉN P. , GÓMEZ-DUMM CÉSAR L.
Published: June 2012

Acute exercise (swimming in water at 24°C) provoked marked changes in the fine structure of the mitochondria of heart muscle in rats. At 60 min after the start of exercise, a large number of invaginations appeared in the mitochondrial wall, suggesting the existence of replication phenomena. In the interior of the invaginations, electron-dense granules considered to be ribosomes were seen. After 90 and 120 min of swimming, mitochondria of unusual size, measuring several sarcomeres in length, were seen. The enlarged mitochondria showed no structural alterations. The planimetric measurement of the micrographs of myocardium of the control animals and of those that exercised showed a statistically significant increase in the whole mitochondrial mass in the latter. One the basis of these observations it is suggested that acute exercise can produce an increase in the mitochondrial mass of the heart muscle cell in a short time.
Responses of the Sino-atrial Node to Change in Pressure in the Sinus Node Artery
Authors: HASHIMOTO KOROKU , TANAKA SHIGEO , HIRATA MINORU , CHIBA SHIGEOTOSHI
Published: June 2012

The sino-atrial node area was perfused selectively through the right atrial artery in 76 dogs. The relationship between changes in the blood pressure in this artery and sinus node rhythmicity was studied in 56 hearts in which the major blood supply to the sinus node artery came from the right atrial artery. A reciprocal relation was observed between changes of blood pressure in the sinus node artery and the sinus rate. Some characteristics were: (1) The negative chronotropic effect induced by raising the blood pressure was linearly related to the Degrees of pressure change and more prominent than the positive chronotropic effect induced by reducing the pressure. (2) This relationship was most prominent in a limited range between 20 and 100 mm Hg. (3) Dichloroisoproterenol, atropine, hexamethonium, reserpine and vagotomy did not modify these responses. It is concluded that this localized mechanosensitivity of the sinus node to changes in arterial pressure may be responsible for the regulation of the heart rate in the lower range of blood pressure and that complete regulation of the heart rate is achieved physiologically in combination with the reflexes through the carotid and aortic nerves.
Behavior of Vascular Beds In the Human Upper Limb at Low Perfusion Pressure
Authors: COLLINS GEOFFREY M. , LUDBROOK JOHN
Published: June 2012

A technique of venous occlusion pressure plethysmography was used to examine the behavior of blood flow in the hand and forearm during reduced perfusion pressure. The trend of flow following sudden reduction in perfusion pressure was recorded, and steady-state pressure-flow curves were constructed. Epinephrine iontophoresis allowed discrimination between forearm skin and muscle blood flow. Pressure-flow curves for the hand were parabolic, convex to the pressure axis, and passing close to the zero point. There was no progressive change in flow once perfusion pressure and flow were initially reduced. Autoregulation was evident in forearm muscle and was more marked in chronically sympathectomized limbs. When perfusion pressure was reduced, blood flow fell, then rose to a new, steady level. Pressure-flow curves were concave to the pressure axis and intersected it at close to zero.
Normal Oxidative Phosphorylation in Mitochondria from the Failing Heart
Authors: SOBEL BURTON E. , SPANN JAMES F. , POOL PETER E. , SONNENBLICK EDMUND H. , BRAUNWALD EUGENE
Published: June 2012

Oxidative phosphorylation was measured polarographically in mitochondria isolated from normal ventricles and from the ventricles of guinea pigs and cats with experimental heart failure produced by constriction of the aorta or pulmonary artery. The presence of heart failure was proved by the study of myocardial mechanics in vitro, by cardiac catheterization, and by postmortem examination. Mitochondria from failing ventricles had normal oxidative phosphorylation, and P-O ratios, respiratory control, oxygen consumption and ATPase activity did not differ from those of mitochondria from normal hearts. Results were the same whether incubations were performed at 25° or 37°C and whether glutamate or pyruvate and malate were used as the substrate. Mitochondria showed functional deterioration, probably due to fatty acid accumulation, when incubated for more than 10 min at 37°C or when isolated from hearts made hypoxic in vivo for as little as 3 min. The results of this study suggest that decreased myocardial contractility in experimental heart failure is not due to an intrinsic defect in mitochondrial function.
Pulmonary and Circulatory Effects of Fibrinopeptides
Authors: BAYLEY TREVOR , CLEMENTS JOHN A. , OSBAHR ALBERT J. , Szerdahelyi Frank P.
Published: June 2012

Bovine fibrinopeptide B and human fibrinopeptide A given in minute concentrations to rabbits, dogs, and lambs caused pulmonary hypertension, decreased effective pulmonary blood flow, decreased lung compliance, decreased ventilatory conductance, increased frequency and volume of ventilation, and increased differences in arterial and alveolar Pco
2
and Po
2
. These effects appeared immediately after injection of the peptides into the lesser circulation, increased for 15 to 30 min, and were detectable for as long as 70 min. Mean aortic pressure, heart rate, stroke volume, left and right atrial pressures, and cardiac output showed no systematic changes after injection of these peptides. On the contrary, bovine fibrinopeptide A given in equimolar doses elicited none of the pulmonary responses but induced increases in heart rate, stroke volume, and cardiac output without consistent changes in mean pulmonary or aortic pressure. These responses appeared within 3 min, increased for 5 to 10 min, and disappeared within an hour. Some possible relationships of fibrinopeptides to clinical syndromes characterized by respiratory distress, hypoxemia, pulmonary vasoconstriction, and diminished lung compliance are briefly discussed. It is speculated that the lung may be an active site of fibrinopeptide catabolism and that accelerated fibrinogen-fibrin conversion may cause pulmonary failure through fibrinopeptide-induced vasoconstriction and reduction in compliance.
Baroreceptor Reflexes and Autoregulation of Cerebral Blood Flow in the Dog
Authors: RAPELA CARLOS E. , GREEN HAROLD D. , DENISON ADAM B.
Published: June 2012

Cerebral venous outflow was measured in anesthetized dogs at the confluence of the sagittal and straight sinuses, with the lateral sinuses occluded. Denervation of the carotid bifurcation increased systemic arterial pressure (+25.8;
SE
±7.7 mm Hg) and decreased cerebral vascular conductance (-0.018;
SE
±0.005 ml/min · mm Hg); stimulation of the carotid sinus nerve decreased systemic arterial pressure and increased cerebral vascular conductance. Graded constrictions of the common carotid arteries induced transient responses of the cerebral blood flow that were characteristic of an autoregulatory process. Plots of the steady-state pressures and flows during the decreases of perfusion pressure were concave toward the pressure axis, were similar before and after denervation of the carotid bifurcation, and were indicative of autoregulation.

We conclude that pressoreceptors in the carotid bifurcation or other pressoreceptors in systemic vessels upstream from the carotid bifurcation are not necessary for the control of the "tone" of the cerebral vasculature or in the mechanism of the autoregulation of cerebral blood flow.
Effects of Frequency of Contraction and lonic Environment on the Responses of Heart Muscle to Acetylcholine
Authors: FRIEDMAN WILLIAM F. , BUCCINO ROBERT A. , SONNENBLICK EDMUND H. , BRAUNWALD EUGENE
Published: June 2012

The effects of frequency of contraction and of external calcium and sodium concentration on the inotropic actions of acetylcholine (ACh) on isolated mammalian myocardium were examined. In stimulated left atria of cats, ACh reduced tension development, i.e. exerted a negative inotropic effect, which became more striking as the frequency of contraction was increased and was inhibited by atropine. In cat papillary muscles studied at a low frequency (<42/min), high concentrations of ACh augmented tension development, i.e. produced a positive inotropic effect, which was enhanced by atropine. At high frequencies (>72/min) this positive effect of ACh was abolished. Moreover, at high frequencies, ACh consistently further reduced the normal increment in tension associated with increasing frequency. The magnitude of the positive inotropic action of ACh on papillary muscle was abolished by lowering the extracellular [Na
+
] and varied inversely with the extracellular [Ca
2+
]. These findings were interpreted in terms of a dual action of ACh on the myocardium: (1) an action on the muscarinic receptor that reduces contractility and may be blocked with atropine, and (2) a direct effect on cellular membrane permeability to Ca
2+
that stimulates contractility and may be reduced by prior elevation of intracytoplasmic [Ca
2+
].
On the Mechanism of Vascular Leakage Caused by Histamine-Type Mediators
Authors: MAJNO GUIDO , GILMORE VIRGINIA , LEVENTHAL MONIKA
Published: June 2012

A current hypothesis maintains that the vascular leakage induced by histamine, serotonin, and bradykinin is brought about by a hydrostatic mechanism: The larger veins are said to contract; the venules are therefore submitted to an increase in pressure, which causes their wall to give way. To test this hypothesis, vessels of an exposed striated muscle (rat and rabbit cremaster) were photographed while treated with the above-mentioned substances; the occurrence of vascular leakage was tested by the intravenous injection of carbon black (carbon labeling). All animals were under barbiturate anesthesia, given a neuromuscular blocking agent (gallamine triethiodid), and were maintained by artificial respiration, according to a technique previously described. In 72 rats and 4 rabbits, the first event observed was arteriolar dilatation. Constriction of a small vein was observed in only 1 in 76 experiments (in two other cases it was doubtful). It is concluded that venous spasm cannot account for the leakage induced by the mediators of the histamine type, though such leakage may be enhanced by venous spasm whenever it may occur. An alternative mechanism is proposed and discussed: Histamine-type mediators cause vascular leakage by a direct effect on the venular endothelium, which is induced to contract.
Redistribution of Renal Blood Flow Produced by Furosemide and Ethacrynic Acid
Authors: BIRTCH A. G. , ZAKHEIM R. M. , JONES L. G. , BARGER A. C.
Published: June 2012

Outer medullary blood flow (
85
Kr method) is markedly reduced by furose-mide and ethacrynic acid injected into the renal artery of unanesthetized dogs; juxtamedullary cortical flow is also decreased. Anatomic localization of the redistribution was verified by autoradiography and by silastic injection studies. The injected specimens demonstrated a relative increase in the resistance of the peritubular capillaries of the juxtamedullary cortex and outer medulla, the blood supply of the juxtamedullary tubules, Henle's loops and collecting ducts; the vasa recta were dilated. Total renal blood flow (Doppler Flowmeter) decreased 10% 1 min after injection, and then gradually began to increase at 2 to 3 min, reaching levels 25 to 30% above control as cortical blood flow increased. The vasodilatation in the cortex is probably localized in the pars radiata. The onset of the diuresis coincided with the decrease in renal blood flow, and persisted after total renal blood flow returned to control value. Thus, the time course of the dicresis correlated more closely with the sustained decrease in juxtameduiary and outer medullary blood flow.
Effects of Chronic Excess Salt Ingestion
Authors: DAHL LEWIS K. , KNUDSEN KNUD D. , HEINE MARTHA A. , LEITL GEORGE J.
Published: June 2012

A strain of rats that will predictably develop experimental hypertension by means of different techniques was used to study NaCl-induced hypertension. Observations were continued for 1 year after weaning unless death intervened. Among groups of rats on 0.4, 1, 2, 4, and 8% NaCl chow, respectively, blood pressures generally rose as dietary NaCl increased. Average blood pressures ranged from 146.8 mm Hg in the group on the lowest, to 210.2 mm Hg in the group with the highest NaCl intakes. Morbidity and mortality also increased. Even transient high NaCl diets were capable of inducing permanent hypertension; 4 of 34 rats on 8% NaCl chow for only 2 weeks after weaning had pressures of 180 to 206 mm Hg, although most rats did not become significantly more hypertensive than those on the low (0.4%) NaCl diet. When this same diet was continued for a total of 6 weeks in a group of 29 animals, the blood pressure averaged 198.6 mm Hg. The age at which the high NaCl intake began also influenced the course of the hypertension. Weanling rats rapidly developed fulminating hypertension on the high NaCl diet. After 3 months on this regimen, the average pressure of 40 rats exceeded 200 mm Hg, and 35 animals were dead or terminally ill. In rats that were older when high NaCl diets were started, hypertension developed more slowly and was less fulminant. Among 38 rats in which NaCl was not begun until 3 or 6 months past weaning, blood pressures averaged 175 to 180 mm Hg after 3 months on NaCl; 31 appeared in good health but none survived 8 months.
Atriogenic Mitral Valve Reflux: Diastolic Mitral Incompetence Following Isolated Atrial Systoles
Authors: WILLIAMS JOHN C. P. , O'DONOVAN T. PAUL B. , VANDENBERG RUSSELL A. , STURM RALPH E. , WOOD EARL H.
Published: June 2012

Cardiac and aortic pressures were recorded after stellate ganglionectomy and vagotomy. Acute heart block was produced by injecting the atrioventricular node, and atrial and ventricular systoles were controlled electronically to occur independently or in any desired relationship. Angiocardiograms recorded on video tape after injections of 4 ml 69% Renovist into the left ventricle were analyzed with a videodensitometer able to detect small refluxes of contrast medium into the left atrium and correlate them with phases of the cardiac cycle. When ventricular driving was temporarily suspended but atrial driving continued, pressure records indicated mitral valve closure after each atrial systole, but reflux of contrast medium into the atrium occurred after each systole not followed by a normally sequenced ventricular systole. Driving with a 2: 1 atrioventricular stimulation resulted in reflux, with the alternate atrial contraction dissociated from ventricular systole. Thus, the mitral valve was not effectively closed by atrial systoles that were not followed by normally sequenced ventricular systoles.
Measurement of Nonlinearity in the Arterial System of the Dog by a New Method
Authors: DICK D. E. , KENDRICK J. E. , MATSON G. L. , RIDEOUT V. C.
Published: June 2012

One method of measurement of the nonlinearity of a vascular system is to apply a sinusoidal input perfusion flow and to examine the resultant pressures and flows at the input and elsewhere in the system for harmonic content. Unfortunately the pump may contain much higher harmonic content than will be generated by the nonlinearities in the arterial system of dogs. If two fixed flow pumps are available and can simultaneously be used in parallel to perfuse the system at two incommensurate frequencies
f
1
and
f
2
, then the appearance of intermodulation frequencies, such as
f
1
+
f
2
,
f
1
-
f
2
, will provide a sensitive measurement of nonlinearity. This scheme has been used, and the recorded measurements have been reduced to power spectral density form with the aid of a hybrid computer. The most important result of these studies is that the intermodulation scheme is shown to be a very sensitive method for detecting the presence of nonlinear characteristics in the arterial system of the dog, even though the system was found to be nearly linear. This scheme also proved useful in detecting changes in nonlinearity since, when injection of norepinephrine considerably increased the mean pressure, the nonlinearity was significantly less.
Patterns of Sympathetic Nerve Projections onto the Canine Heart
Authors: RANDALL WALTER C. , SZENTIVANYI MATHIAS , PACE JOHN B. , WECHSLER JAMES S. , KAYE MICHAEL P.
Published: June 2012

Major branches from right and left sympathetic ganglia were electrically stimulated while force of contraction was recorded from multiple areas of the right and left ventricles. Stimulation of the stellate ganglia generally elicited alterations in force of contraction from all test segments, but excitation of selected nerve trunks induced responses in highly localized regions of the heart. Ablation of narrow strips of epicardium resulted in obliteration of contractile responses in specific, highly localized regions of the heart; thus a major fraction of the sympathetic innervation of the ventricular chambers is by way of the epicardial plexus. The anterior surface of the right ventricle is supplied by projection pathways arising within the immediately subepicardial regions of the right A-V groove and, to a lesser extent, from the tissues immediately adjacent to the left anterior descending artery. The left ventricle receives minor projections from the right A-V groove with major projections from subepicardial tissues along the left anterior descending artery. In some animals there also exists a definite left ventricular supply from the region of the left A-V groove. Whereas the thoracic vagi send dense projections to the atria, and particularly to nodal tissue, they also supply both ventricles with inhibitory and augmentor fibers. Although isolated cardiac nerves may carry predominantly sympathetic or parasympathetic fibers, many show rich intermingling of these fibers in trunks distal to the caudal cervical ganglion.
Distribution of Ions and Water between Tissue Compartments in the Perfused Left Ventricle of the Rat Heart
Authors: PAGE ERNEST , PAGE EVA Gross
Published: June 2012

Left ventricles from rat hearts were perfused through the coronary blood vessels for periods up to 90 minutes with solution containing radioactively labeled sulfate, sucrose, urea, glycerol, or chloride. Urea and glycerol equilibrate with all of tissue water. By contrast,
35
SO
4
and sucrose-
14
C equilibrate very rapidly with 40% of total water and slowly with an additional 20%; they are excluded from 40% of the tissue water. The two "cellular" compartments (C
2
, which equilibrates slowly with SO
4
and sucrose, and C
3
, from which SO
4
and sucrose are excluded) both lose water when hearts are perfused with a solution made hypertonic with NaCl. Chemical analyses for K, Na, and Cl, and measurements of the rate of equilibration of
36
C1 show that C
2
has low contents of Cl and Na. Experiments in which extracellular NaCl was replaced osmole for osmole by KCl according to the method of Boyle and Conway suggest that the boundaries of C
2
and C
3
may have different ionic permeabilities. These observations indicate that the division of mammalian heart muscle into tissue compartments is more complex than conventionally assumed, a conclusion reached by Bozler for frog heart muscle. They are inconsistent with the usual assumption that cardiac cellular water is homogeneous.
Left Ventricular Myocardial Contractile Response to Aortic Constriction in the Hyperthyroid Guinea Pig
Authors: GOODKIND M. JAY
Published: June 2012

Maximum left ventricular systolic pressure response to aortic constriction served as a measure of myocardial contractility in anesthetized euthyroid and hyperthyroid guinea pigs. This response in hyperthyroid guinea pigs (155.4 ± 1.40 mm Hg) was significantly greater than in euthyroid animals (147.3 ± 1.33 mm Hg) (
P
<.001) and developed at a lower end-diastolic pressure in hyperthyroid (11.27±0.418 mm Hg) than in euthyroid guinea pigs (14.15±0.521 mm Hg) (
P
<.001). Beta-adrenergic receptor blockade with propranolol decreased the heart rate in both groups of animals but did not alter the contractile response. After propranolol, the heart rate of the hyperthyroid animals, though decreased, was still greater than that of euthyroid controls. Cardiac stimulation at a rate similar to that of the hyperthyroid animals (430 beats/min) did not change the left ventricular contractile response of normal guinea pigs. It is concluded that myocardial contractility in hyperthyroid guinea pigs is greater than normal. Increased activity of the sympathetic nervous system is probably present in hyperthyroidism, is reflected in the tachycardia, but does not appear to increase myocardial contractility. The increased myocardial contractility therefore is probably due in large part to a direct effect of thyroid hormone on cardiac muscle.
Computer Analysis of the RR Interval-Contractility Relationship during Random Stimulation of the Isolated Heart
Authors: MEIJLER FRITS L. , STRACKEE JAN , VAN CAPELLE FRANS J. L. , DU PERRON JEANNY C.
Published: June 2012

Hemodynamic variability in patients with atrial fibrillation may originate from a direct influence of the variations in RR intervals on myocardial contractility. With the aid of a computer the serial autocorrelation function and the histogram of the RR intervals of patients with atrial fibrillation receiving no medication were produced. The RR intervals were randomly distributed and the histograms rather skew. Next, random rhythms with histograms matching those of the patients were produced with a radioactive source and a Geiger-Müller counter. These rhythms were used to stimulate isolated perfused rat hearts to study the relationship between the RR interval and a number of contractile parameters. The ECG and the isotonic contractions were digitized and processed by the computer. Serial crosscorrelation coefficients were computed between the RR interval on the one hand, and contraction height, contraction area, and maximum of the first derivative of the contraction on the other hand. The zero order crosscorrelation coefficient between the RR interval and contraction height was 0.6, between the RR interval and contraction area 0.8, and between the RR interval and maximum of first derivative 0.5. Although small, the first and second to approximately the tenth order coefficients were definitely negative. It is concluded that during a random rhythm the contractile parameters of an isolated heart are strongly related to the preceding RR interval. It is conceivable that this relation contributes to the variability of hemodynamic parameters during atrial fibrillation in man.
Cardiac Actions of Glucagon
Authors: LUCCHESI BENEDICT R. , Brown Jeanne , Laidlaw Barbara , Rockiki Deonna
Published: June 2012

Glucagon increased heart rate and contractile force in the anesthetized dog and increased isometric tension in the isolated dog papillary muscle. The positive inotropic and chronotropic responses were not abolished or reduced by previous administration of the beta-receptor blocking agent propranolol, in doses of 0.5 mg/kg. Glucagon increased the force and rate of cardiac contraction even when cardiac-depressant doses of propranolol, 2 mg/kg, had been given. Previous treatment with reserpine (1.0 mg/kg on each of 3 consecutive days) failed to diminish the positive inotropic and chronotropic effects of glucagon. However, previous administration of tyramine, 0.05 mg/kg, which resulted in a positive inotropic response in the dog, significantly reduced the glucagon-induced positive inotropic response. Theophylline, 10 mg/kg, likewise prevented the inotropic action of glucagon without preventing the positive inotropic effect of calcium chloride. The increase in isometric tension produced by glucagon in the isolated dog papillary muscle was prevented during simultaneous exposure of the muscles to acetylcholine. The results of these studies are discussed in reference to the known metabolic actions of glucagon and the catecholamines and the possibility that they both share a common mechanism of action mediated through an increase in the intracellular concentration of cyclic 3',5' AMP.
Effects of Sympathetic Nerve Stimulation on the Pulmonary Arterial Tree of the Isolated Lobe Perfused in Situ
Authors: INGRAM ROLAND H. , SZIDON J. PETER , SKALAK RICHARD , FISHMAN ALFRED P.
Published: June 2012

The hemodynamic response to sympathetic nerve stimulation (SNS) was studied in canine lung lobes isolated in situ and perfused with a pulsatile pump. For the same input pulse, both the rate of rise and the rate of fall of pulmonary arterial pressure increased during SNS; the peak systolic pressure was also higher during SNS, whereas diastolic pressure levels were either at, or below, control levels. The increase in pulse pressure produced little or no change in mean pulmonary artery pressure and resistance. During SNS, compliance per unit length in large arteries fell, pulse wave velocity increased, and elastic modulus increased. Phenoxybenzamine produced opposite changes. Norepinephrine injections increased resistance and produced smaller compliance changes than SNS.

Flow loads imposed by short bursts of rapid pump rate at constant stroke volume caused increments of vascular volume which returned to control levels after return to the slower rate. Volume increments were smaller and restoration rates faster during SNS than during control. After phenoxybenzamine, volume increments were larger and restoration rates slower than control.

The results indicate that the distensibility of the large pulmonary arteries and the precapillary bed is decreased during sympathetic stimulation, while calculated resistance is not changed.
Indicator-Dilution Measurement of Cardiac Output with Dissolved Hydrogen
Authors: KLOCKE FRANCIS J. , GREENE DAVID G. , KOBERSTEIN ROBERT C.
Published: June 2012

Dissolved H
2
has been used as an indicator for measuring cardiac output by the techniques of constant-rate injection and sudden, single injection indicator dilution. Because of its low solubility, H
2
is eliminated essentially quantitatively in the lungs and recirculates negligibly. The constant-rate injection technique involves the gas chromatographic measurement of pulmonary (or systemic) arterial H
2
concentration during an infusion of dissolved H
2
into a vena cava (or the left atrium). Measurements in anesthetized dogs agreed well with simultaneous measurements by dye dilution, direct Fick, and direct volumetric techniques. Measurements could be repeated several times a minute, and using a linearly responding platinum electrode, intravascular H
2
concentrations could be recorded continuously. In the sudden, single injection technique, dissolved H
2
was injected into a vena cava (or the left atrium) while monitoring pulmonary (or systemic) arterial H
2
concentration with a chromatographically calibrated platinum electrode. Measurements again agreed with simultaneous measurements by dye dilution, constant-rate injection of H
2
, and the direct volumetric technique. Hydrogen curves could be repeated rapidly and integrated instantaneously. Hydrogen appears to be a useful indicator for rapidly repeated determinations of cardiac output and for measurements of output in situations in which recirculation of conventional indicators limits their usefulness.
Effects of Acute Valvular Regurgitation on the Oxygen Consumption of the Canine Heart
Authors: URSCHEL CHARLES W. , COVELL JAMES W. , GRAHAM THOMAS P. , CLANCY RICHARD L. , ROSS JOHN , SONNENBLICK EDMUND H. , BRAUNWALD EUGENE
Published: June 2012

The effects on myocardial oxygen consumption and mechanics of acute, simulated aortic and mitral regurgitation were studied in open-chest, anesthetized dogs to determine how changes in the mechanical performance of the ventricle alter oxygen consumption. When regurgitation was induced acutely with effective stroke volume (total stroke volume less regurgitant volume) and heart rate held constant, left ventricular end-diastolic volume, total stroke volume, the ejection fraction, left ventricular wall tension, and the extent of shortening of the contractile element and the circumferential fibers all increased. With volumes of regurgitation approaching effective systemic blood flow, oxygen consumption increased only moderately, despite the increases in tension and shortening. When valvular regurgitation was induced while peak ventricular wall tension was held relatively constant, stroke volume doubled and the extent of both contractile element and circumferential fiber shortening increased. Contractile element work in generating tension was unchanged; that which led to fiber shortening increased substantially. Myocardial oxygen consumption did not increase significantly. Thus, marked increases in the efficiency of the contractile elements and myocardial fibers occurred. The low energy cost per unit of work expended in shortening as opposed to that used for tension development therefore allows the excess stroke volume of valvular regurgitation to be maintained at only a small added oxygen cost to the ventricle.
Compressibility of the Arterial Wall
Authors: CAREW THOMAS E. , VAISHNAV RAMESH N. , PATEL DALI J.
Published: June 2012

The assumption of incompressibility has often been applied to the analysis of arterial-wall elasticity; however, the supporting evidence has been incomplete. The present study was designed to explore this problem in greater depth by accurately measuring the changes in tissue volume associated with large, induced strains on 11 thoracic aorta segments excised from dogs. The radial, circumferential, and longitudinal stresses were measured as the artery was subjected to an internal pressure and longitudinal stretch greater than those in vivo. From these data it was possible to calculate the hydrostatic stress. The associated changes in volume of the aortic wall tissue were measured with a specially designed apparatus. The greatest volumetric strain (ΔV/V) was 0.00165. The bulk moduli obtained by dividing the hydrostatic stresses by the corresponding volume strains averaged 4.44 x 10
6
g/cm
2
. Similar studies were also carried out on the abdominal aorta and the carotid, iliac, and pulmonary arteries. The volumetric strains observed were of the same magnitude. It is concluded that for most practical purposes arteries may be considered incompressible.
Epidemiologic and Genetic Studies of Congenital Heart Disease in the Dog
Authors: PATTERSON D. F.
Published: June 2012

The prevalence rate for cardiovascular malformations in dogs presented to a large university veterinary clinic was 6.8 per 1000. Patent ductus arteriosus, as in man, was found predominantly in females. Breed-specific prevalence rates were significantly greater in purebred dogs than in mongrels, and the breed distributions of patent ductus arteriosus, pulmonic stenosis, subaortic stenosis, persistent right aortic arch, and tetralogy of Fallot were significantly different than would be expected if all breeds were equally susceptible to each type of malformation. On the basis of these observations, two hypotheses were made: (1) Genetic factors are determinants of certain types of congenital heart disease in the dog. (2) These genetic factors have specific effects on cardiac morphogenesis, resulting in specific types of cardiovascular malformations. Preliminary genetic studies confirmed the specific hereditary transmission of valvular pulmonic stenosis in beagles, persistent right aortic arch in German shepherds, and conal septal defects (including ventricular septal defects and tetralogy of Fallot) in keeshonden. The pattern of inheritance of these defects was not consistent with any simple genetic hypothesis. Patent ductus arteriosus in dogs of poodle ancestry and fibrous subaortic stenosis in Newfoundlands were shown provisionally to be transmitted in a manner consistent with autosomal dominant inheritance. The significance of these findings is considered in relation to present and future understanding of the etiology and pathogenesis of congenital heart disease.
Carotid Sinus Reflex Control of Coronary Blood Flow
Authors: FEIGL ERIC O.
Published: June 2012

The role of the carotid sinus reflex in control of the blood flow in the left circumflex coronary artery was studied in nine open-chest dogs anesthetized with chloralose. Flow was measured with an electromagnetic flowmeter. The effects of bilateral common carotid occlusion were examined in a three-part experiment in each dog. (1) Under vagotomy (control) conditions, occlusion of both common carotid arteries resulted in tachycardia, increased blood pressure, and a decrease in coronary artery resistance. (2) After beta-receptor blockade with propranolol, 1.0 mg/kg, carotid sinus hypotension still resulted in increased blood pressure but the tachycardia was blocked, and coronary artery resistance increased. (3) Following rapid cardiac sympathectomy, carotid sinus hypotension still resulted in a reflex rise in systemic blood pressure but coronary resistance remained steady. This demonstrated the reflex nature of the increased coronary resistance observed after beta-receptor blockade. It is concluded that the coronary circulation is under reflex control and that sympathetic coronary artery vasomotion is a part of a carotid sinus reflex.
Measurement of Local Cerebral Blood Flow in the Unanesthetized Rat Using a Hydrogen Clearance Method
Authors: HAINING JOSEPH L. , TURNER M. Don , PANTALL RALPH M.
Published: June 2012

The hydrogen clearance method for measuring local tissue blood flow was adapted for use in the brain of the unanesthetized rat by means of a stainless steel plate screw mounted in the skull as the reference electrode instead of a calomel electrode. Blood flow was measured at 3 sites in the brains of 5 three-month-old rats over a 6-week period. Blood flow in the frontal cortex and the cerebellum for all the animals averaged 79 ± 22 (SD) and 81 ± 25 ml/min/100 g tissue, respectively. The other site, supposedly the hippocampus, exhibited a two-component clearance curve in most cases. The initial rapid component was of questionable validity; the second slow component averaged 110 ± 23 ml/min/100 g. Autopsy revealed that the hippocampal electrode was actually positioned in more than one type of tissue or proximal to an interspace.

Hypoxia (Po
2
= 50 mm Hg) and hypercapnia (produced by inhalation of 10% CO
2
) increased the clearance rates two- to four-fold. The rate of local blood flow and its variability were affected by the state of the animal; anesthesia (sodium pentobarbital) decreased the rate of blood flow as anticipated, and markedly reduced the variation in rate seen in the conscious state.
Velocity of Blood Flow in Normal Human Venae Cavae
Authors: WEXLER LEWIS , BERGEL DEREK H. , GABE IVOR T. , MAKIN GEOFFREY S. , MILLS CHRISTOPHER J.
Published: June 2012

The velocity of flow and pressure in the venae cavae of four normal conscious subjects was studied. Velocity was measured with a catheter-tip electromagnetic transducer. The effects of respiration, Valsalva and Müller maneuvers, coughing, and exercise were studied. Caval blood velocities during breath holding showed marked cardiac pulsations, being maximal at the time of ventricular systole and minimal or reversed at atrial systole. Peak velocities during ventricular systole ranged from 30 to 45 cm/sec in the inferior, and from 10 to 35 cm/sec in the superior, vena cava. A second diastolic forward flow velocity ranged from 36 to 76% of the systolic peak. During inspiration, velocity transiently increased. Reduction of flow velocity in abdominal breathing and the Müller maneuver is consistent with the formation of a local area of inferior vena caval collapse at the diaphragm. During the Valsalva maneuver, abrupt reduction in caval flow was seen that persisted throughout the strain. There was immediate overshoot when the strain was released. Coughing produced a reduction of flow velocity with backflow in the superior vena cava. In leg exercise, inferior caval flow velocity rose immediately, and it remained high during recovery. Marked respiratory velocity variations with inspiratory increases occurred during and after exercise.
Biochemical Correlates of Cardiac Hypertrophy
Authors: NAIR K. G. , CUTILLETTA A. F. , ZAK RADOVAN , KOIDE TADASHI , RABINOWITZ MURRAY
Published: June 2012

Cardiac hypertrophy occurred in mature rats after producing supravalvular aortic stenosis with a specially designed silver clip. For 2 weeks following this procedure, heart weight, body weight, and RNA content of the myocardium were serially determined. Heart weight and RNA content increased within 24 hours of aortic banding, reaching a maximal level in 2 days and remaining elevated during the 2 weeks of observation. Nuclei were isolated and purified from heart muscle homogenates, and changes in RNA polymerase activity following aortic banding were determined. The nearest neighbor frequency of the bases of the RNA synthesized by the polymerase from nuclear preparations was identical in both the banded animals and the sham-operated controls. Both groups could thus be compared on the basis of the enzyme assay. RNA polymerase activity in nuclei from the hearts of banded rats rose rapidly when compared with the activity in sham-operated rats; peak values were reached on the second day, the earliest detectable change being around 12 hours. The increase in RNA polymerase activity represents one of the earliest biochemical events that take place in the myocardium following aortic banding.
Measurement of Umbilical Arterial Blood Flow to the Sheep Placenta and Fetus in Utero
Authors: MAKOWSKI EDGAR L. , MESCHIA GIACOMO , DROEGEMUELLER WILLIAM , BATTAGLIA FREDERICK C.
Published: June 2012

A method of estimating the magnitude and distribution of umbilical blood flow by means of radioactive microspheres in sheep fetuses in utero is described. Simultaneous measurements of total umbilical flow by this method and the steady-state diffusion technique showed agreement within ±11%. In 11 fetuses of 90 to 150 days gestational age, the distribution of umbilical flow to the intercotyledonary chorion was 6.2±0.8% of the total. This information has been used to estimate the effect of venous admixture of cotyledonary and noncotyledonary blood on the umbilical vein-uterine vein concentration difference of inert molecules with flow-limited transplacental clearance.
Myointimal Cells as a Possible Source of Replacement for Endothelial Cells in the Rabbit
Authors: TS'AO CHUNG-HSIN
Published: June 2012

Regeneration of damaged endothelium has been studied by means of mechanical injury to rabbit abdominal aorta and inferior vena cava. Ultrastructural evidence suggests that myointimal cells can become endothelial cells. It is postulated that such a myogenic replacement of endothelial cells may occur under normal circumstances in the aorta. Injury to blood vessels merely accelerates this process.
Synthesis and Turnover of Norepinephrine in the Heart of the Spontaneously Hypertensive Rat
Authors: LOUIS WILLIAM J. , SPECTOR SYDNEY , TOBEI RYO , SJOERDSMA ALBERT
Published: June 2012

The kinetics of norepinephrine (NE) metabolism in the heart was studied in genetically hypertensive and normotensive control Wistar rats. Concentrations of endogenous NE were similar in the two groups. However, rates of synthesis of NE were reduced in these hypertensive rats, whether calculated from the rate of decline (fractional turnover rate) of cardiac tritiated NE (
3
H-NE) after intravenous injection, or estimated from levels of
14
C-NE in the heart after injection of the precursor
14
C-L-tyrosine. In experiments with
3
H-NE the synthesis rate of NE was 30.2 ng/hour/g heart in control and 18.2 ng/hour/g heart in hypertensive rats. The levels of
14
C-NE found in the heart of normotensive rats given
14
C-tyrosine were up to 1.4 times those found in hypertensive rats. These findings indicate a reduced rate of release of NE in this form of hypertension and, rather than implicating NE as a primary factor, suggest a secondary, compensatory mechanism.