bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Hypothermia and Pronethalol on Ionic Correlates of Ouabain Arrhythmias in Dogs
Authors: EI-FIKY S. B. , KATZUNG B. G.
Published: June 2012

The ionic basis of ventricular arrhythmias induced by a cardiac glycoside was studied in pentobarbital-anesthetized dogs. The effects of ouabain alone and in combination with hypothermia or pronethalol on myocardial and plasma Na
+
and K
+
were determined. Hypothermia (26°C) and pronethalol (15 mg/kg, iv) had similar effects on the standard lead II of the EGG, i.e., a decrease in heart rate and increases in P-R, QRS, and Q-T intervals. In the absence of ouabain, hypothermia and pronethalol each produced small and inconsistent changes in intracellular Na
+
and K
+
concentrations. Both hypothermia and pronethalol were found to significantly increase the threshold toxic dose of ouabain required to produce a ventricular arrhythmia within the test period of 90 minutes. Both pronethalol and hypothermia effectively prevented ouabaininduced changes in myocardial Na
+
and K
+
when arrhythmias were prevented. When sufficient ouabain was given to produce an arrhythmia, there was always a significant fall inmyocardial K
+
. In unprotected and in hypothermic animals, these arrhythmias were also associated with a significant increase in left ventricular Na
+
. The effect of ouabain on Na
+
was not significant in pronethalol-treated dogs.
Biochemical Correlates of Cardiac Hypertrophy
Authors: KOIDE TADASHI , RABINOWITZ MURRAY
Published: June 2012

Cardiac hypertrophy was produced in rats by banding the ascending aorta. Increases in heart weight and RNA content occurred within 48 hours, indicating that hypertrophy develops rapidly. The total RNA content and the specific radioactivity of RNA labeled with
3
H-uridine were determined. The rate of RNA synthesis was estimated from these data and from the specific radioactivity of the myocardial uridine nucleotide pool. The rate of RNA synthesis in hearts of banded animals averaged four times greater than controls on the second postoperative day and about two to three times greater on the fourth to fifth postoperative days. An expansion of the myocardial uridine nucleotide pool was observed in banded rats, but the size of the myocardial adenosine nucleotide pool was not changed. No changesin base composition of 28S, 18S, or 4S RNA were observed following cardiac hypertrophy.
Effect of Enhanced Contractility on the Left Ventricular Response to Vagus Nerve Stimulation in Dogs
Authors: LEVY MATTHEW N. , ZIESKE HARRISON
Published: June 2012

In the canine isovolumetric left ventricle preparation, stimuli were applied to the efferent end of a transected cervical vagus nerve. The changes in left ventricular systolic pressure in response to vagal stimulation were compared under control conditions and when ventricular contractility was enhanced by various kinds of inotropic stimulation-left stellate ganglion stimulation, paired pacing, calcium chloride infusions, aminophylline infusions, and acetylstrophanthidin injections. Vagal stimulation under control conditions caused mean decreases in pressure in the various groups ranging from 13.2 to 16.2% of the control level. The depressant effect of vagal stimulation was potentiated during sympathetic stimulation, in confirmation of previous findings; the mean decrease in pressure produced by vagal stimulation during concurrent sympathetic stimulation varied from 20.1 to 20.8%. Calcium and aminophylline infusions had no significant effect on the ventricular response to vagal stimulation; the percent reductions in pressure caused by vagal stimulation were 18.1 and 15.5%, respectively. However, the response to vagal stimulation was markedly attenuated during paired pacing and after acetylstrophanthidin; the percent reductions in pressure caused by vagal stimulation were 5.0 and 9.4%, respectively. The potentiation of the response to vagal stimulation during increased cardiac sympathetic activity probably represents a specific adrenergic-cholinergic interaction.
Bilateral Carotid Sinus Control of Ventricular Performance in the Dog
Authors: MARTIN PAUL J. , LEVY MATTHEW N. , ZIESKE HARRISON
Published: June 2012

Left and right carotid sinus pressures were independently varied while the left ventricular systolic pressure was recorded in an anesthetized canine preparation with an isolated, isovolumetric left heart. Intrasinus pressures were changed in steps of 50 mm Hg to produce either an increase or decrease in pressure from a mean level of 150 mm Hg. The response to eight combinations of increases and decreases in left- and right-sided pressures was examined. Blockade of the sympathetic impulses to the heart produced a loss of response of left ventricular systolic pressure when the intrasinus pressure was decreased from 150 to 100 mm Hg. Parasympathetic blockade produced a loss of response to an increase in pressure from 150 to 200 mm Hg. Left ventricular systolic pressure was more sensitive to a decrease in pressure from 150 to 100 mm Hg in the right sinus than in the left, but there was no difference in sensitivity between left and right sides when intrasinus pressure was raised from 150 to 200 mm Hg. The summation pattern of the response to simultaneous steps in left and right pressure was mutually facilitative for steps from 150 to 100 mm Hg and mutually inhibitory for steps from 150 to 200 mm Hg. The entire system was simulated with a hybrid computer model consisting of separate functional relations used to represent the baroreceptors, central nervous system, and left ventricle. Due to the baroreceptor characteristics and other nonlinearities, the simulation results suggest that a careful distinction should be drawn between transient and steady-state responses when assessing the relative role of each autonomic division in any baroreceptor reflex.
Interaction of Transmembrane Potentials in Canine Purkinje Fibers and at Purkinje Fiber-Muscle Junctions
Authors: MENDEZ CARLOS , MUELLER WILLIAM J. , MERIDETH JOHN , MOE GORDON K.
Published: June 2012

Interactions between Purkinje fibers and ventricular muscle were studied in canine Purkinje-papillary muscle preparations. The change in duration of action potentials across the junctions between Purkinje fibers and papillary muscle was continuously graded, not abrupt. The transmembrane action potentials were longest in the false tendons and progressively shorter in more peripheral fibers. The responses of terminal Purkinje fibers and of neighboring muscle cells differed little in duration. The shortest action potentials were found in muscle fibers located in regions devoid of specialized tissue (tip of papillary muscle). These results suggest that the intercellular connections, including those at the junctions, offer relatively low resistance to current flow. During repolarization the current flowing between neighboring elements with intrinsically different repolarization times should therefore minimize the disparity in action potential durations on the two sides of the junctional site; a continuously graded change in duration would result. Because of this continuous gradation, premature ventricular responses initiated at the tip of the papillary muscle could be blocked, depending on the degree of prematurity, at various levels in muscle fibers functionally close to terminal Purkinje fibers or within the Purkinje system.
Preservation of Ventricular Function by Adrenergic Influences during Metabolic Acidosis in the Cat
Authors: ROCAMORA JOSE M. , DOWNING S. EVANS
Published: June 2012

Although metabolic acidemia reduces the contractility of cardiac muscle in isolated preparations, it does not do so to the same extent in intact animals or those with a functioning sympathoadrenal system. The present study was designed to determine if the resistance of the heart to acidemia is the consequence of concurrent adrenergic influences on the myocardium. The function of the cat's left ventricle was examined in a preparation that allowed control of aortic pressure, cardiac output, heart rate and temperature. The arterial blood pH, Po
2
, Pco
2
, and temperature were continuously measured. Acidemia was produced either endogenously by temporarily diminishing perfusion of peripheral tissues, or by infusion of 0.5N lactic acid. Studies were made before and after beta-receptor blockade with propranolol, 0.25 to 0.5 mg/kg iv or im. In eight control animals, reduction of pH from 7.34 to 7.08 failed to diminish contractility. In 14 animals with beta-receptor blockade, reduction of pH to 7.02 reduced contractility by about 25% (
P
<.001). Correction of the acidemia by infusion of tris(hydroxymethyl)aminomethane returned contractility to approximately 95% of control. Rapid reduction of pH transiently diminished contractility in control animals and severely depressed those with beta-receptor blockade. These data support the position that sympathoadrenal activity is necessary to preserve ventricular function in the presence of severe metabolic acidemia.
Anatomical and Ultrastructural Study of the Electrophysiological Atrioventricular Node of the Rabbit
Authors: DEFELICE LOUIS J. , CHALLICE CYRIL E.
Published: June 2012

The structure of the tissue forming the atrioventricular node of the rabbit heart was studied with the light and the electron microscope. The observations were correlated and compared with the electrophysiological properties of the region. A technique was developed which allows identification of tissue examined by microscopy with that examined using microelectrode techniques to within 0.5 mm. Although the cells which form the connecting neck between the atrial tissue and the His bundle are basically muscle cells, their development has led to tissue structure different from that of the remaining myocardium. This tissue often displayed structural characteristics similar to those observed in pathological skeletal and cardiac muscle. Variation in the abundance of "tight" intercellular junctions in the region of the node were noted. The possible significance of the morphological characteristics in terms of electrical impulse transmission is discussed, and some tentative suggestions are made concerning the mechanisms by which the slow impulse conduction is effected in this region.
Study of Luminal Coronary Collateral Circulation in the Beating Canine Heart
Authors: HAUSWIRTH OTTO
Published: June 2012

The action of halothane on sinoatrial, ventricular, and Purkinje fibers was studied by means of intracellular microelectrodes. Rabbit atrial fibers were not very sensitive to even high (2%) concentrations of halothane. Sheep Purkinje fibers showed a significant hyperpolarization from 82 mv to 87 mv, a marked shortening of the duration of the action potential from 370 msec to 233 msec, and a diminution of the overshoot from 30 mv to 21 mv under the influence of 1% halothane. The rate of rise was now significantly rchanged with this concentration. In the presence of 2% halothane the resting potential did not differ significantly from the value obtained with 1% halothane. The duration of the action potential and of the refractory period were further diminished to 165 msec and to 109 msec, respectively. The rate of rise was now significantly reduced to 245 v/sec and the overshoot further decreased to 17 mv. Conduction time was increased by about 20% with 1% halothane and more than twofold with 2% halothane. Ventricular fibers of sheep did not show significant changes of the resting potnetial under the influence of 2% halothane. However, the duration of the action potential was markedly shortened from 338 msec to 231 msec, the effective refractory period was significantly reduced from 295 msec to 208 msec, and the overshoot decreased from 21 mv to 11 mv. Possible mechanisms underlying these changes and which may cause arrhythmias are discussed.
Central Nervous Integration of the Circulatory and Respiratory Responses to Arterial Hypoxemia in the Rabbit
Authors: KORNER PAUL I. , Uther John B. , White Saxon W.
Published: June 2012

Neural integration during arterial hypoxia was studied in sham-operated, rhinencephalic, thalamic, high mesencephalic, and pontine rabbits, 3 hours after operation under halothane anesthesia. All preparations except the pontine recovered normal movement and posture 40 to 60 minutes after the operation, and effects on the resting circulation specifically ascribable to transection were small. Activation of diencephalic, and to a lesser extent of rhinencephalic, centers was necessary to produce the large increase in autonomic peripheral resistance effect and the autonomic slowing of heart rate characteristic of normal rabbits. In animals with only pontine and high mesencephalic centers, the autonomic peripheral resistance effect was smaller and there was an autonomic rise in heart rate. The neocortex and rhinencephalon exerted inhibitory influences related to the effects of hyperventilation. Suprabulbar respiratory mechanisms were also activated during hypoxia, with diencephalic mechanisms limiting the reflex response mediated by the pontine centers and the cortex exerting disinhibitory effects on the diencephalic centers. The cardiorespiratory response at different degrees of hypoxia probably depends on differences in relative magnitude of inputs from the arterial chemoreceptors, baroreceptors, and lung inflation receptors, producing different degrees of excitation and inhibition of the various suprabulbar and bulbar centers.
A Qualitative Distinction between the Beta-Receptor-Blocking and Local Anesthetic Actions of Antiarrhythmic Agents
Authors: SHINEBOURNE ELLIOT , WHITE ROGER , HAMER JOHN
Published: June 2012

Fragmented cardiac sarcoplasmic reticulum was isolated by differential centrifugation from canine myocardium. The effects of propranolol, quinidine, lidocaine (lignocaine) and tetracaine (amethocaine) on calcium uptake in sarcoplasmic reticulum in vitro were then measured. All the drugs are antiarrhythmic agents with local anesthetic activity, but propranolol and quinidine are known also to have beta-receptor-blocking actions in that they can prevent the cardiac effects of isoprenaline and depress the myocardium. Lidocaine and tetracaine do not generally depress the heart and had no effect on the calcium uptake, but propranolol and quinidine both significantly inhibited it. It was concluded that the antiarrhythmic actions of propranolol (and quinidine) may be independent of beta-receptor-blocking activity, and that the safety of lidocaine as an antiarrhythmic agent may be related to a lack of effect on the sarcoplasmic reticulum.
Changes in the Activities of Lysosomal Enzymes in Infarcted Canine Heart Muscle
Authors: RAVENS KURT G. , GUDBJARNASON S.
Published: June 2012

Experimental myocardial infarction was produced in 32 mongrel dogs. The changes in activity of four lysosomal enzymes (acid phosphatase, glucuronidase, deoxyribonuclease, and γ-glutamyl-transpeptidase) were examined in the soluble and the particle-bound fraction. The pattern of changes in free and particle-bound enzyme activity observed was similar for all four enzymes. During the first 48 hours after coronary occlusion, the particle-bound enzyme activity was decreased, while the free activity was moderately increased, reflecting the autolytic phase of cell and tissue destruction. Between the second and the sixth day, the soluble hydrolytic enzyme activity was maximal and the particle-bound activity was slowly increasing. During this period, the main part of tissue degradation and removal of cell debris takes place. Ten days after myocardial infarction the free hydrolytic activity had returned to control values, but the particle-bound enzyme activity was four to ten times higher in the infarcted tissue than in the control muscle.
Mechanism of the Effects of Furosemide on Renin Secretion in Anesthetized Dogs
Authors: VANDER ARTHUR J. , CARLSON JOYCE
Published: June 2012

Furosemide was administered to anesthetized dogs in priming doses of 0.1, 0.5, or 2.5 mg/kg followed by the same amounts per hour as infusion. When sodium and water balances were maintained constant by the continuous replacement of urinary losses with isotonic saline, the renal venous renin activity (and renin release) was not altered by the 0.1 mg/kg dose but was significantly increased by the two larger doses. This increase was manifest within 5 to 10 minutes. The larger doses also increased mean arterial pressure but did not change plasma sodium or glomerular filtration rate. Renal plasma flow was increased by the 2.5 mg/kg dose but not by the 0.5 mg/kg. In another group of dogs in which salt depletion was allowed to occur, 0.1 mg/kg produced an increased renin release within 30 minutes; this increase was completely reversed by the replacement of sodium and water losses. In this group of dogs, the glomerular filtration rate decreased and then returned to control values after restoration of fluid balance. It is hypothesized that the two higher doses of furosemide stimulated renin release by directly inhibiting macula densa sodium transport, and that the reported effects of all natriuretics can be explained in terms of a single macula densa theory.
Myocardial Contractile Response to Norepinephrine, Isoproterenol, and Calcium Chloride in Hyperthyroid Guinea Pigs
Authors: Goodkind M. Jay
Published: June 2012

Myocardial contractility, measured as the maximum left ventricular systolic pressure response to aortic constriction, is greater than normal in the hyperthyroid guinea pig. The effect of inotropic agents on this response was determined in anesthetized, open-chest, euthyroid, and hyperthyroid guinea pigs. Norepinephrine and isoproterenol in single doses, 1 µg/kg, and isoproterenol infused intravenously, 1, 4 and 10 µg/kg/min, caused a smaller increase in myocardial contractile response to aortic constriction in hyperthyroid than in euthyroid animals. Hyperthyroid guinea pigs also responded to an infusion of calcium chloride, 11 mg/kg/min, with an increase in maximum systolic pressure which was less than normal. With each drug the maximum systolic pressure level attained during aortic constriction was greater in the euthyroid than in the hyperthyroid animals. Cardiac pacing of euthyroid guinea pigs at 430 beats/min, a rate similar to the spontaneous rate of the hyperthyroid guinea pig, did not alter the inotropic response to infused calcium, though single injections and intravenous infusions of isoproterenol had less of an effect than in the spontaneously beating normal heart. These results suggest that the increased myocardial contractility of the hyperthyroid guinea pig may have reached a near maximum level. As a result, the added inotropic effects of isoproterenol and calcium in these animals are less than in normal controls.
Simultaneous Measurements of Radii and Wall Thickness of Microvessels in the Anesthetized Rat
Authors: Baez Silvio
Published: June 2012

The purpose of this investigation was to measure the radius and wall thickness of small blood vessels in mesentery and striated (cremaster) muscle in the anesthestized rat. Using the method of image-splitting, the vessel images were sheared at magnifications of 3,OOOx and 6,500x on the video screen.

In the resting state, the mean lumen values for the thinnest portion of endothelial capillary were 4.1 ± 1.2µ (SD) in cremaster and 5.6 ± 1.3µ (SD) in mesentery. Lumen and total diameter were also greater at several levels of precapillary arterioles in mesentery than similar vessels in cremaster, suggesting that smaller vessel size in cremaster might be characteristic of this tissue. Vasoconstriction of up to 50% from resting state is associated with an increase in wall thickness and a decrease in lumen to wall ratio due to a disproportional decrease in radius (inner greater than outer radius). Similarly, an increase in vessel radius in a proportion 4 to 1 (inner greater than outer) was sustained up to about 60% of vasodilatation.

In 13 out of 14 vessels, little or no change in wall cross-sectional area occurred in the face of marked changes in lumen cross-sectional area (–95%,+205%). This strongly suggests that other modifications such as changes in length, swelling, or shrinkage would be relatively unimportant during dynamic changes in wall thickness.
Chronotropic Effect of Cardiac Glycosides in Cats, Dogs, and Rabbits
Authors: Ten Eick Robert E. , Hoffman Brian F.
Published: June 2012

We have tested the widely accepted hypothesis that digitalis, in nontoxic concentration, can act directly on cells of the sinoatrial pacemaker to cause slowing. The effect of autonomic nerves on sinoatrial cells was eliminated either by chronic cardiac denervation or by use of autonomic blocking agents such as atropine, 0.5 mg/kg, and propranolol, 2 mg/kg, or MJ-1999, 3 mg/kg. When the effects of autonomic nerves were eliminated, acetylstrophanthidin, 0.120 mg/kg, failed to cause slowing of sinus rate in the anesthetized cat and the anesthetized dog. Similarly, ouabain, 5 x 10
-7
M, and acetylstrophanthidin, 1.5 µg/ml, after prior administration of autonomic blocking agents failed to cause slowing of the isolated rabbit right atrium perfused with Tyrode's solution. These results indicate that the sinus slowing caused by cardiac glycosides may be mediated entirely by alteration of the neural control of the heart and that the drug, in nontoxic concentration, does not have a direct negative chronotropic action on the mammalian sinoatrial node.
Inhibition of Incorporation of Leucine into Myocardial Proteins of the Rat by Antiarrhythmic Agents
Authors: Beller Barry M. , Mongillo Stephen
Published: June 2012

Incorporation of tritiated leucine into myocardial proteins was inhibited at low concentration by quinidine, procaine amide, and diphenylhydantoin, but not by lidocaine or propranolol. This inhibition could be demonstrated in vitro and when the animals were treated with these agents. The relationship between this finding and myocardial depression produced by these antiarrhythmic agents is not known but may reside in general depression of cellular metabolism and protein synthesis or in inhibition of synthesis of a specific membrane carrier protein.
Influence of Sympathetic Nerve Stimulation on Ventricular Function in the Newborn Lamb
Authors: Downing S. Evans , Talner Norman S. , Campbell Alexander G. , Halloran Katherine H. , Wax Howard B.
Published: June 2012

Cardiac responses to supramaximal electrical stimulation of postganglionic sympathetic nerve fibers were studied in 17 lambs, 10 hours to 3 days of age. In all lambs left ventricular contractility increased within 3 seconds and was unaltered by atropine, ganglionic blockade, or nerve sectioning proximal to the stimulating electrodes but was abolished by beta-receptor blockade. The responses were repeatedly demonstrated in two lambs subjected to bilateral adrenalectomy. Acidemia (pH 6.9) produced by lactic acid infusion failed to diminish the inotropic responses. Intravenous or leftatrial injections of tyramine produced chronotropic and inotropic responses comparable to sympathetic nerve stimulation. Glucagon, 50 to 200 µg/kg, failed to elicit cardiac responses in lambs from 1 to 60 days of age. It is concluded that sympathetic neural mechanisms may strongly influence myocardial contractility in the newborn lamb and that these responses are independent of adrenal medullary release of catecholamines. These findings further suggest that the lamb possesses a myocardial adenyl cyclase system that responds only to catecholamines and may be blocked with propranolol.
Parasympathetic Control of Coronary Blood Flow in Dogs
Authors: FEIGL ERIC O.
Published: June 2012

The role of the vagus in the control of coronary blood flow was studied in chloralose-anesthetized dogs with open chests. Propranolol, 1.0 mg/kg iv, was used for beta-receptor blockade. Heart rate was maintained at a constant level with atrial and ventricular pacing. Left circumflex coronary artery blood flow was measured with an electromagnetic flowmeter. The experimental design accounted for the four major determinants of coronary blood flow: (1) aortic pressure, (2) myocardial systolic compression, (3) alterations in myocardial oxygen tension and metabolism secondary to changes in contractile force, (4) neural control. Efferent stimulation of the cut cervical vagi (30 Hz, 2 msec, 8-10 v) resulted in decreased aortic blood pressure and increased coronary blood flow. Late diastolic coronary artery resistance fell to 58% of the control value after 5 seconds of vagal stimulation. Atropine, 0.5 mg/kg iv, blocked these effects. It is concluded that direct parasympathetic coronary vasodilation results from vagal stimulation, which is independent of vagal chronotropic and inotropic effects.
Cholinergic Innervation of the Autotransplanted Canine Kidney
Authors: WEITSEN HOWARD A. , NORVELL JOHN E.
Published: June 2012

The degeneration of acetylcholinesterase-positive nerve fibers in 11 canine renal autotransplants was investigated with the thiocholine method of Karnovsky and Roots as modified for cryostat sections. Seven renal hila were also examined by silver impregnation and thiocholine techniques. Total denervation was demonstrated in only 3 of 11 autotransplants; the other 8 showed variable degrees of degeneration, from almost total to very little. Acetylcholinesterasepositive nerve fibers accompanied the renal, interlobar, arcuate, and interlobular arteries and the afferent arterioles and vasa recta. Acetylcholinesterase activity was apparent in glomeruli but was greatly diminished or abolished by renal perfusion with normal saline before histologic procedures were begun. Discrete autonomic ganglia were seen in the renal hila. We believe these acetylcholinesterase-positive ganglion cells (also found scattered along hilar nerve bundles) are the source of the nerve fibers which remain intact and viable following vascular division during transplantation.
Myogenic Tone in Isolated Perfused Vessels: OCCURRENCE AMONG VASCULAR BEDS AND ALONG VASCULAR TREES
Authors: UCHIDA EIICHI , BOHR DAVID F.
Published: June 2012

In situ studies yield only indirect evidence as to whether non-neurogenic vascular tone results from an intrinsic myogenic tendency of the smooth muscle cell to contract or is due to stimulation of the muscle by some vasoactive humoral influence of the environment. In the current study, small resistance vessels from different vascular beds, from various levels of the arterial tree, and from several species were isolated and perfused with physiological salt solution. Under these conditions the environment is devoid of any vasoactive, in-situ, humoral influence, and tonic contraction would have to be of myogenic origin. Myogenic tone was consistently present in smooth muscle from some vascular beds, whereas it was absent from other beds. Myogenic tone was more prevalent in smaller vessels (50 to 100µ o.d.) than in larger ones (100 to 400µ o.d.). Significant differences in this property were observed among the species studied. We conclude that, contrary to the properties classically assigned it as a multiunit smooth muscle, most vascular smooth muscle from resistance vessels is intrinsically and spontaneously active.
Examination of the Intrarenal Hematocrit Ratio with the Technique of Circulatory Stop-Flow in Dogs
Authors: Selkurt Ewald E. , Laurence Richard J.
Published: June 2012

Estimates of the intrarenal hematocrit ratio vary widely, depending on the techniques used for its determination. Computation of blood volume from the product of mean transit time of labeled erythrocytes and albumin, and minute volume blood flow, yields values averaging approximately 90% of the systemic vessel hematocrit. To the other extreme are values that are slightly less than half of the systemic hematocrit ratio based on the determination of total renal blood volume by labeled red cells and albumin. Intermediate values are obtained by methods involving draining the blood from the kidney and measuring its hematocrit ratio. The current investigation, by a technique of circulatory stop-flow, has shown that a substantial fluid shift occurs in the kidney within 2 minutes of circulatory arrest, so that interstitial fluid, supplemented by fluid reabsorbed by the nephrons, dilutes the erythrocytes within the peritubular capillaries to reduce the hematocrit ratio to almost half of the systemic figure. The drainage methods are subject to error as a result of this mechanism, but if such fluid shifts are taken into account, values for the intrarenal hematocrit closer to the ratio of systemic blood can be anticipated.
Reflex Cardiovascular Effects of Epicardial Stimulation by Acetylstrophanthidin in Dogs
Authors: Sleight Peter , Lall Amrit , Muers Martin
Published: June 2012

Application of 25 to 100 µg of acetylstrophanthidin to the epicardium of the left ventricle of anesthetized and unanesthetized dogs caused hypotension and bradycardia without signs of discomfort. The response developed after an average latency of 8 seconds and lasted up to 12 minutes. Cooling the cervical vagi to 8 to 10°C or prior application of 0.1% procaine hydrochloride to the epicardium of the heart blocked the response. The response was, therefore, a reflex; the sensory receptors were located in the surface layers of the left ventricle. Electrophysiological recordings from single and multifiber preparations of the right recurrent cardiac nerve showed that the receptors for this reflex were mechanoreceptors whose fibers belonged to the C group. The sinus bradycardia caused by digitalis glycosides may result partly from excitation of these receptors.
Mathematical Analysis of Oscillatory and Non-oscillatory Recovery of Contractility after a Rested-State Contraction and Its Modification by Calcium
Authors: Posner Christian J. , Berman David A.
Published: June 2012

Recovery of contractility after a rested-state contraction in rat ventricle proceeded in two phases and is described by equations that are solutions of a nonhomogeneous second-order differential equation. The recovery can be characterized by a damping ratio defined in terms of the constants of the homogeneous portion of the differential equation. When calcium concentration was elevated, the usual smooth recovery curve underwent oscillatory variation and thus became less damped. There was a shift in phase between oscillation in recovery and in resting tension after a rested-state contraction. A control system is proposed to regulate relaxation and subsequent recovery of contractility. Possible mechanisms for an effect of calcium on such a control system are discussed.
Study of the Sympathetic Vasoconstrictor Nerves to the Vessels of the Dog Hind Limb
Authors: DONALD DAVID E. , FERGUSON DAVID A.
Published: June 2012

In anesthetized dogs, the vasoconstrictor nerves to the vessels of the hind limb left the spinal cord in the anterior spinal nerve roots from T-10 through L-4 levels. Maximal vasoconstrictor responses occurred on stimulation of the T-12, T-13, and L-l roots; none occurred on stimulation of roots caudal to L-4. The nerves first entered the lumbar paravertebral chain at or above L-1; the last point of entry was at the L-4, L-5 level. No fibers left the lumbar chain at L-1, L-2, and L-3 levels. The first point of exit was at L-4, and nerves continued to leave as far distal as S-1, The most caudal point examined. The maximal response to stimulation of the lumbar chain was at the L-4, L-5 level. With a single exception, the responses to electric stimulation of the anterior spinal nerve roots, lumbar chain, or sympathetic ganglia were confined to the vessels of the ipsilateral limb. In 22 dogs with unilateral sympathectomy (L-2 through L-7), changes in hind-limb vascular resistance were induced reflexly or by electric stimulation of the anterior spinal roots. The results indicated that sympathetic control of the resistance vessels of the hind limb was still absent 77 days after sympathectomy.
Mechanism Initiating Ventricular Fibrillation Demonstrated in Cultured Ventricular Muscle Tissue
Authors: SANO TOYOMI , SAWANOBORI TOHRU
Published: June 2012

Ventricular muscle strips of the rat embryo heart were used for tissue culture preparations without adding trypsin. Fibrillation-like arrhythmia was induced by adding aconitine or strophanthin, and the potentials were recorded with one or two microelectrodes. The tracing by one microelectrode was no different than tracings from fibrillating adult mammalian hearts. The size and shape of the action potential varied beat by beat, and its time of appearance was quite irregular and rapid. But, when tracings obtained simultaneously by two microelectrodes were compared, most of the action potentials were roughly synchronous and thus unlike adult cardiac fibrillation. This ruled out the possibility of multiple reentry or multifocal origin in this preparation.

Because of the small size of the cultured tissue, reentry of the excitation wave probably could not occur, and the conclusion that fibrillation originated from a single focus is thus supported. Three varieties of the onset of fibrillation, i.e., gradual increase of tachycardia with progressively steeper slow diastolic depolarization, a prominent positive afterpotential followed by a negative afterpotential, and abortive action potentials superimposed on the repolarization of the preceding action potentials or on the negative afterpotential, supported the unifocal onset.
Response of the Main Pulmonary Artery of Dogs to Neuronally Released Versus Blood-Borne Norepinephrine
Authors: INGRAM ROLAND H. , SZIDON JAN P. , FISHMAN ALFRED P.
Published: June 2012

The effects of sympathetic nerve stimulation and of norepinephrine infusions on the dynamic elastic properties of the main pulmonary artery were studied in 20 anesthetized, open-chest dogs. Pulmonary arterial pressure and diameter were linearly related between 5 to 45 mm Hg and at heart rates of 40 to 200 beats/min. Sympathetic nerve stimulation changed the stiffness (pressure-diameter slope) of the pulmonary artery by +35%; infusion of norepinephrine (0.25 µg/kg/min) by only +14%. Diameter intercepts, determined by extrapolation of the linear pressure-diameter line, were unchanged during stimulation, but decreased significantly during the infusion of norepinephrine. Local application of norepinephrine to the wall duplicated the changes produced by sympathetic nerve stimulation.

Histologically, the arrangement of smooth muscle in the outer layers of the media of the artery suggested linkage of smooth muscle with continuous elastic fibers, whereas smooth-muscle cells of the deeper layers of the media appeared to connect with each other, and elastic fibers were discontinuous. The topical application of elastase to the outer wall effected a loss of elastic fibers in the outer layers of the media. After elastase, neither stimulation nor norepinephrine infusions increased stiffness; diameter intercepts decreased with both.

The observations are consistent with the idea that stiffening of this artery during nerve stimulation is produced by contraction of smooth muscle attached to elastic fibers and that the anatomical arrangement for stiffening is located in the outer layer of the media, where the sympathetic nerve endings are located. In contrast, blood-borne norepinephrine stimulates predominantly the inner layers.
Adrenergic Mechanisms in the Effects of Histamine in the Pulmonary Circulation of the Cat
Authors: COLEBATCH H. J. H.
Published: June 2012

Histamine constricts airways and pulmonary blood vessels in isolated lungs, but is said to dilate pulmonary blood vessels in intact animals. The present experiments test the hypothesis that histamine only constricts pulmonary blood vessels, and that dilatation depends on epinephrine released by histamine from the adrenal glands. In cats anesthetized with pentobarbital, the difference in pressure between the pulmonary artery (PA) and left atrium (LA) was related to pulmonary blood flow measured by dye dilution before, and at intervals of 0.5 to 2 minutes after PA injection of histamine. In intact or vagotomized cats histamine increased PA-LA pressure difference and pulmonary blood flow, but calculated pulmonary vascular resistance (PVR) decreased significantly at 1 minute; control values were restored in 4 minutes. In adrenalectomized cats, histamine (10 to 40 µg) increased PA-LA pressure and PVR, but did not change pulmonary blood flow. After beta-receptor blockade with propranolol, histamine (10 to 20 µg) had the same effect as in adrenalectomized cats. After adrenalectomy or propranolol, the histamine-induced increase in PVR was prolonged. When histamine had increased PVR in adrenalectomized cats, epinephrine (5 µg iv) reduced PA-LA pressure and PVR. Histamine infusion (5 µg/kg/min iv) decreased PVR in intact cats, increased PVR in adrenalectomized cats, and when epinephrine (5 µ/kg/min) was also infused, decreased PVR in adrenalectomized cats. The results support the proposed hypothesis. Release of histamine locally in the lungs may encourage distribution of both blood and gas flows away from damaged and toward normal respiratory tissue.
Increased Rate of Sealing in Beating Heart Muscle of the Toad
Authors: DE MELLO W. C. , DEXTER D.
Published: June 2012

The influence of stimulation on the healing-over of myocardial cells of the toad was investigated. The rate of sealing was markedly increased in beating muscles. This effect of stimulation on the healing process varied with the frequency of the stimulus and depended on the extracellular Ca concentration. Low sodium solutions increased the rate of sealing in stimulated muscles but not at rest. Some evidence is presented that the increased Ca influx which accompanies stimulation activates the reactions involved in the sealing process.
Metabolic Effects of Ethanol on the Rabbit Heart
Authors: KIKUCHI T. , KAKO K. J.
Published: June 2012

Ethanol in saline solution (15%, v/v) was infused into anesthetized rabbits at a rate of 0.494 ml/min for the first 12 minutes and then at 0.247 ml/min for 108 minutes. Three hours after the infusion, heart triglyceride and lipoprotein lipase were assayed. Oxidation and esterification of fatty acids (palmitate
-14
C as an indicator) were assessed by using either tissue homogenates or perfused hearts taken from the rabbits. Oxidation-reduction states of the perfused hearts were examined by measuring the tissue levels of dehydrogenase-linked substrates. The infusion of ethanol resulted in 180% increase in heart triglyceride content, but the infusion of norepinephrine (3 µg/kg/min) did not change the content. No change in plasma free fatty acids and triglyceride or heart lipoprotein lipase activity was detected. Addition of ethanol had little effect on the distribution of palmitate
-14
C in the lipids of tissue slices and homogenates. On the other hand, prior infusion of ethanol resulted in depression of
14
CO
2
production (70 and 50%) and enhanced fatty acid esterification into triglyceride (270 and 170%) both in homogenates and perfused hearts. Mitochondrial and cytoplasmic redox states were shifted to more oxidized states by ethanol infusion. It is postulated from these results that an accumulation of triglyceride in the rabbit heart in response to ethanol administration is a result of decreased fatty acid oxidation rather than of increased triglyceride uptake or increased fatty acid synthesis.
Effects of Acetylstrophanthidin on Isolated Veins of the Dog
Authors: BRENDER DAVID , STRONG CAMERON G. , SHEPHERD JOHN T.
Published: June 2012

Acetylstrophanthidin, 1.0 to 10.0 µg/ml, caused contraction of strips of the lateral saphenous vein of the dog in an organ bath at 37°C. The superior mesenteric vein, which exhibited spontaneous activity in the organ bath, responded to acetylstrophanthidin with an almost immediate increase in tension and an increased frequency of contractions; this was followed by a sustained contraction which had the same time lag as the contraction of a saphenous vein strip from the same dog. In strips from both veins, the contraction was depressed by cooling and augmented by warming, an effect opposite to that seen with norepinephrine-induced contractions. A latent period of 10 to 60 minutes preceded the contraction of the saphenous vein; during this time, the vein showed increased reactivity to added norepinephrine, 5-hydroxytryptamine, acetylcholine, barium chloride, increased bath concentration of K
+
, and decreased bath concentration of Na
+
. The increased reactivity and contraction still occurred after catecholamine depletion of the vein by chronic lumbar sympathectomy and in umbilical veins, which are devoid of adrenergic nerves. In addition to its direct constrictor action on cutaneous and mesenteric veins, acetylstrophanthidin sensitized cutaneous veins to vasoactive agents and to changes in ionic environment. These actions did not depend on the presence of norepinephrine in the veins.
Influence of Duration of Cholesterol Feeding on Esterification of Fatty Acids by Cell-Free Preparation of Pigeon Aorta
Authors: CLAIR RICHARD W.ST. , LOFLAND HUGH B. , CLARKSON THOMAS B.
Published: June 2012

Influence of duration of cholesterol feeding on esterification of fatty acids and hydrolysis of cholesteryl esters was studied in cell-free preparations of aorta from White Carneau pigeons. Esterification of fatty acids required ATP and CoA; greater than 80% of the esterifying activity was located in the particulate fraction obtained by centrifugation at 105,000x
g
(after a preliminary centrifugation at 1000x
g
). Fatty acids were incorporated most efficiently into phospholipid, primarily (82%) lecithin. Greater than 87% of the fatty acid was esterified at the 2-position. During 8 months of cholesterol feeding, incorporation of oleic acid into phospholipids and triglycerides increased relatively little (less than double that of controls); no changes were seen before 1 month. Esterification of oleic acid to cholesterol was increased after 2 weeks of cholesterol feeding (before gross lesions were seen), eventually reaching a maximum increase of 30- to 50-fold. Cholesterol was esterified by transfer of fatty acyl-CoA to cholesterol, a mechanism similar to that described for liver and adrenal cortex. Little if any cholesterol esterification occurred when lecithin labeled at the 2-position with oleic acid-l-
14
C was used as substrate. The relationship between duration of cholesterol feeding and hydrolysis of cholesteryl oleate could not be evaluated since results depend directly on an unknown extent of equilibration of substrate with pre-existing cholesteryl ester pools.
Reflex Vascular Responses to Stimulation of Chemoreceptors with Nicotine and Cyanide
Authors: CALVELO MANUEL G. , ABBOUD FRANCOIS M. , BOLLARD DENNIS R. , ABDEL-SAYED WADIE
Published: June 2012

Experiments were done to characterize the vascular responses to stimulation of aortic and carotid chemoreceptors and to identify the efferent components of the sympathetic system which are activated in different vascular beds. The chemoreceptors were stimulated with nicotine and cyanide in anesthetized and artificially ventilated dogs. The gracilis muscle and hindpaw were isolated and perfused with blood at constant flow. Changes in perfusion pressure reflected changes in total vascular resistance, and changes in small vein pressure reflected changes in venous resistance. The results indicate that stimulation of carotid and aortic chemoreceptors activates selectively efferent adrenergic constrictor fibers supplying prevenous resistance vessels in the gracilis muscle and venous resistance vessels in the paw. In contrast, there was a dilatation of prevenous resistance vessels in the paw caused by activation of efferent sympathetic dilator fibers and not by withdrawal of sympathetic constrictor tone. The dilatation was not mediated through the release of acetylcholine, histamine, or bradykinin nor through beta receptors. Bilateral denervation of the carotid sinus and body and bilateral vagotomy abolished the reflex responses caused by injections of the chemicals. These responses were not the result of activation of baroreceptors since they were not reproduced during electrical stimulation of the carotid sinus nerve.
Evidence for the Renal Conversion of Angiotensin I in the Dog
Authors: FRANKLIN W. G. , PEACH M. J. , GILMORE J. P.
Published: June 2012

Experiments were carried out on perfused canine kidneys in situ to determine if renal conversion of angiotensin I occurs. Various concentrations of decapeptide produced an immediate increase in renal vascular resistance when injected directly into the renal artery. Since the decapeptide is biologically inactive, the increased resistance was interpreted as indicating generation of angiotensin II. The extent of renal conversion of angiotensin I to angiotensin II was estimated to be approximately 19% in the normal dog. This percent conversion was reduced to about 10% in dogs maintained on high salt and DOCA for 7 to 10 days.
Movement of Norepinephrine through the Media of Rabbit Aorta
Authors: BEVAN JOHN A. , TöRöK JOZEF
Published: June 2012

The entry and movement of norepinephrine through the media of the isolated rabbit thoracic aorta has been investigated using an isotopic frozen section technique. After 1-minute exposure of the intimal surface of a helical strip to Krebs bicarbonate solution containing tritiated norepinephrine (
3
H-NE), the
3
H material was distributed throughout the thickness of the wall. The highest concentration occurred at the innermost layer of the media and gradually decreased toward the adventitial side. The shape of the tritium distribution curves was not significantly changed by previous treatment of aortic strips with either cocaine, phenoxybenzamine or the MAO and COMT inhibitors, pargyline and tropolone, respectively. Temperature reduction to 27°C had no significant effect on the tritium distribution curves. The apparent diffusion coefficient for
3
H-NE calculated for movement into the extracellular (inulin) space of the media was 7.29 x 10
-7
cm
2
/sec. This relatively slow rate of diffusion is probably due to physical barriers such as elastic lamellae within the tunica media.
Electrogenic Suppression of Automaticity in Sheep and Dog Purkinje Fibers
Authors: VASSALLE MARIO
Published: June 2012

Driving Purkinje fibers at a fast rate is followed by a temporary suppression of spontaneous activity, "overdrive suppression." The mechanism of this suppression was studied in Purkinje fibers perfused in vitro and stimulated for variable periods of time at selected rates. The overdrive procedures caused an initial decrease in maximum diastolic potential below control followed by a late increase above control. After the overdrive, the slope of diastolic depolarization was decreased and the threshold voltage more positive
2
, these changes were responsible for the temporary suppression of spontaneous activity. After the cessation of 2-minute overdrive, the increase in maximum diastolic potential subsided gradually over a period of 2 to 5 minutes. At higher [K]
o
, the effect of overdrive on membrane potential was reduced. Substitution of Na
+
with Li
+
or exposure to 2,4-dinitrophenol abolished the late hyperpolarization during overdrive. The membrane resistance was not altered after an overdrive period. The results suggest that driving ventricular Purkinje fibers at a rate higher than their intrinsic rate causes an initial loss of K
+
and the activation of an electrogenic Na
+
pump. The activation of the electrogenic pump is the major mechanism responsible for overdrive suppression.