bluuebunny/crossref_metadata_2025 huggingface dataset:
An oscillatory current in sheep cardiac Purkinje fibers.
Authors: Vassalle M , Mugelli A
Published: June 2012

The inward current ("oscillatory current") which may be present after the end of a depolarizing clamp was studied in sheep cardiac Purkinje fibers by means of a voltage-clamp method. The following results were obtained. In order to appear, the oscillatory current (Ios) requires a previous depolarization to approximately or equal to -20 mV or beyond and a repolarization to approximately or equal to -40 mV or to more negative potentials. The Ios requires a minimum duration of the depolarizing clamp and becomes larger with longer clamps. With repolarization to more negative potentials (approximately or equal to 90 mV), Ios becomes smaller and may disappear. Also Ios can be triggered twice if the potential is clamped to two different levels in succession. By several procedures which modify the other known currents (fast Na+ current, slow inward current, early outward current, plateau current Ix1 and pacemaker current), it can be demonstrated that Ios is not due to their oscillatory behavior and can occur in the absence of any one of them. Interventions which increase the contractile force presumably by increasing intracellular calcium stores enhance the Ios or may make it appear. In fact, these interventions may extend the voltage range over which Ios appears. These interventions include lowering potassium, increasing calcium, trains of depolarizing clamps, and administration of norepinephrine and of strophanthidin. It is concluded that Ios is a physiological event which is enhanced by certain procedures, and it appears to be of much importance in drive-induced arrhythmias under different conditions.
The histological lateral border of acute canine myocardial infarction. A function of microcirculation.
Authors: Factor S M , Okun E M , Kirk E S
Published: June 2012

Studies from this laboratory have shown that the border of a 24-hour canine infarct is histologically sharp and is composed of numerous interdigitating peninsulas of necrotic and normal tissue. To see if this sharp boundary is spatially related to the capillary beds of occluded and non-occluded arteries, the left anterior descending artery (LAD) was ligated in five mongrel dogs. Twenty-four hours later, white silicone rubber (Microfil) was injected into the LAD distal to the ligature; simultaneously and under the same pressure, red Microfil was injected into the left main coronary artery (LMCA). In hematoxylin and eosin sections from the border of the infarct, capillaries supplied by the LAD (white) were either in areas of necrosis, in normal epicardium or, rarely, in normal tissue along the lateral boundary; those supplied by the LMCA (red) were almost always in normal regions. Quantitative evaluation of this relationship revealed that the majority of the vessels in the normal and necrotic tissue were concordant (i.e., that normal tissue was supplied by the LMCA, and necrotic tissue by the LAD). However, a small zone of vascular discordance, averaging approximately 30 micrometers in width, was present along the infarct boundary, possibly representing a narrow border zone of little consequence. Hence, the complex interdigitation of normal and necrotic tissue in the lateral border of an infarct is predominantly a function of the interdigitation of the capillary beds supplied by the occluded and nonoccluded arteries.
Hyperemia of the aortic wall in atherosclerotic monkeys.
Authors: Heistad D D , Armstrong M L , Marcus M L
Published: June 2012

The aortic wall is nourished by diffusion from the aortic lumen and from vasa vasorum in the adventitia and outer layers of media. Intimal proliferation in atherosclerosis might be expected to reduce the effectiveness of diffusion from the lumen and increase dependence on nourishment by vasa. This study was performed to determine whether there is increased perfusion of the aortic wall by vasa vasorum in atherosclerosis. We used microspheres to measure flow through vasa in normal and atherosclerotic cynomolgus monkeys. Blood flow to inner layers of the thoracic and abdominal aorta was less than 1 ml/min X 100 g in normal monkeys, and there was a minimal increase in atherosclerotic monkeys. Flow to the outer layers of the thoracic and abdominal aorta was 1.3 +/- 0.9 and 2.2 +/- 0.8 ml/min per 100 g in normal monkeys. Flow to outer layers of the thoracic and abdominal aorta was increased in atherosclerotic monkeys to 17 +/- 8.9 and 31 +/- 12 ml/min per 100 g (P less than 0.05 vs. normal). Thus there is increased perfusion of the atherosclerotic aorta, particularly in the outer layers. During maximal vasodilation induced by infusion of adenosine, flow through vasa was 3- to 8-fold greater in atherosclerotic than in normal monkeys. This finding suggests that proliferation of new vessels, rather than dilation of existing vessels, accounts for the increase in blood flow through vasa. We speculate that hyperemia of the aortic wall in atherosclerosis may be in part a compensatory response to increased oxygen requirements and possibly to ischemia produced by intimal proliferation and a resulting increase in diffusion distance.
Afterpotentials and triggered activity in hypertrophied myocardium from rats with renal hypertension.
Authors: Aronson R S
Published: June 2012

We have found that afterpotentials can be induced selectively in hypertrophied myocardium from rats with renal hypertension. Three kinds of afterpotentials were recorded by standard microelectrode techniques: early afterdepolarizations, delayed afterdepolarizations, and early afterdepolarizations. The first two kinds of afterpotentials could give rise to triggered spontaneous activity, whereas the last kind did not. Delayed afterdepolarizations were induced in hypertrophied fibers exposed to Tyrode's solution containing high extracellular calcium ([Ca2+]o = 7.2-12 mM) and early afterdepolarizations occurred in hypertrophied fibers exposed to Tyrode's solution containing tetraethylammonium (TEA = 10-30 mM). Neither of these treatments produced afterpotentials in normal myocardium. We found that delayed afterdepolarizations became larger when the stimulation frequency, number of preceding driven beats, or [Ca2+]o was increased. The coupling interval from the upstroke of the last driven action potential to the peak of the delayed afterdepolarization decreased when the stimulation frequency or number of preceding driven beats increased. Hypertrophied fibers treated with high [Ca2+]o that gave rise to triggered activity showed a characteristic relationship between delayed afterpotential magnitude and drive cycle length. In hypertrophied muscles treated with TEA, triggered activity developed from an early afterdepolarizations but terminated with a delayed afterdepolarization. The occurrence of afterpotentials in hypertrophied, but not in normal myocardium, appears to reflect the development of an important electrophysiological alteration that may predispose hypertrophied fibers to develop arrhythmias.
Electrophysiological effects of the optical isomers of disopyramide and quinidine in the dog. Dependence on stereochemistry.
Authors: Mirro M J , Watanabe A M , Bailey J C
Published: June 2012

We studied the electrophysiological effects of the optical isomers of disopyramide and quinidine on canine cardiac Purkinje fibers. Conventional microelectrode techniques were employed to study the effects of racemic disopyramide, (+)-disopyramide, (-)-disopyramide, quinidine, and quinine. Racemic disopyramide, (+)-disopyramide, and quinidine prolonged action potential duration (APD) measured at 90% repolarization. In contrast, (-)-disopyramide and quinine shortened APD. These directionally opposite effects on repolarization were observed throughout 60 minutes exposure to drug and were concentration-dependent. All five components reduced dV/dt of phase 0, increased conduction time, and increased the current requirement for all-or-none depolarization. The effects of all five compounds on dV/dt, conduction time, and current requirements were time- and concentration-dependent. Our results indicate that the stereochemical configurations of disopyramide and quinidine determine their effects on repolarization of cardiac Purkinje fibers.
Responses of pulmonary allograft and cheek pouch arterioles in the hamster to alterations in extravascular pressure in different oxygen environments.
Authors: Davis M J , Gilmore J P , Joyner W L
Published: June 2012

The responses to changes in transmural pressure were investigated in pulmonary allograft and cheek pouch arterioles in two oxygen environments. Neonatal hamster lung tissue was transplanted into adult hamster cheek pouches. After vascularization (8-10 days), pulmonary and cheek pouch vessels were observed by intravital microscopy in hamsters anesthetized with pentobarbital. By gassing the suffusion solution (bicarbonate-buffered Ringer's) (pH 7.4 at 35-37 degrees C) with either low oxygen (95% N2/5% CO2) or high oxygen (75% N2/5% CO2/20% O2) and after sealing the top of the chamber, extravascular pressure was altered by varying the fluid volume of the closed chamber. Changes in arteriolar diameters in response to positive and negative square-wave pressure pulses were quantified using a video micrometer and close-circuit TV system. Pulmonary arterioles showed a passive dilation or constriction in response to increases or decreases in transmural pressure (+/-20 mm Hg). These responses were not altered either by changes in PO2 or nitroprusside. In contrast, cheek pouch arterioles showed myogenic responses by constricting when transmural pressure was increased and vice versa. These responses were potentiated at high PO2 and abolished with nitroprusside. It is concluded that a myogenic response is dominant in cheek pouch arterioles but not in pulmonary arterioles under these conditions. These latter observations are consistent with results obtained from isolated, intact lung.
Excitation, conduction, and reflection of impulses in isolated bovine and serum cardiac purkinje fibers.
Authors: Jalife J , Moe G K
Published: June 2012

When an impulse arrives at an area of impaired conductivity, a slowly rising electrotonic potential may bring the distal tissue to threshold after a delay imposed by the passive electrical properties of the system and by the time-dependent changes of these properties during diastole. This phenomenon can be demonstrated in Purkinje strands in which an area of depressed conductivity has been induced by the impedance of a sucrose gap and can be mimicked by the application of relatively long current pulses of low amplitude. The functional refractory period, defined as the shortest interval between two distal responses both propagated across the gap, was determined by the application of premature stimuli at progressively earlier intervals. The time course of the recovery of excitability as well as the conduction intervals could be varied almost at will by manipulating the electric impedance between proximal and distal ends of the fiber. When the time of activation of the distal end across the gap exceeded the absolute refractory period of the proximal segment, the impulse reflected back as a closely coupled premature beat. Time-dependent changes in the passive electrical properties of the depressed segment may set the conditions for reflection. The results suggest the possibility of reflection as a mechanism for premature beats and demonstrate obligatory shifts in the patterns of premature reentrant activity accompanying changes in basic cycle length. These experiments provide important clues for the distinction between reentrant and parasystolic mechanisms.
Interrelationships between regional left ventricular function, coronary blood flow, and myocellular necrosis during the initial 24 hours and 1 week after experimental coronary occlusion in awake, unsedated dogs.
Authors: Roan P G , Buja L M , Izquierdo C , Hashimi H , Saffer S , Willerson J T
Published: June 2012

This study examined the relationships between the left ventricular (LV) regional function, regional myocardial blood flow (RMBF), and myocellular necrosis after sudden proximal occlusion of the left anterior descending coronary artery (LAD) in 36 awake, unsedated dogs. Net wall thickening during systole (NET) was used to assess regional LV function, was expressed as percent control, and was measured with chronically implanted ultrasonic crystals. RMBF was measured with 8- to 10-micrometer radioactive microspheres. In regions with a moderate degree of functional loss, NET fell to 35.3 +/- 2.2% of control at 5 minutes when RMBF fell from 1.9 +/- 0.08 to .086 +/- 0.09 ml/g per min (P less than 0.05). No significant change occurred in midwall or epicardial RMBF. The relationship between endocardial flow and NET was non-linear (r = 0.69, P less than 0.0001). In these segments, subsequent changes in RMBF were unrelated to corresponding functional alterations through 24 hours. In segments with paradoxic systolic wall thinning RMBF fell in endocardial, midwall, and epicardial layers; endocardial ischemia was most severe (0.30 +/- 0.05 ml/g per min). Segmental myocellular necrosis was most severe in the endocardial layer and correlated significantly with both RMBF and segmental function. Myocellular necrosis increased in severity as flow was reduced below 70-75% of normal. Thus, in this model of LV ischemia, (1) regional LV functional loss is most sensitive to reductions in endocardial RMBF; (2) subsequent increases in RMBF are largely unassociated with functional recovery; (3) transmural ischemia results in paradoxical systolic wall thinning.
Factors influencing vascular hyporesponsiveness to angiotensin II.
Authors: Adamick R , Gold M E , Hayes S , Coleman R , McCreary J T , Sabatini S , Arruda J A , Kurtzman N A
Published: June 2012

Bartter's syndrome is characterized, in part, by hyporesponsiveness to the pressor effect of exogenous angiotensin II (AII). This has been attributed to volume contraction, hypokalemia, and/or increased prostaglandin (PG) levels. In order to investigate factors responsible for a diminished response to the pressor effect of AII, rats were made hypokalemic or volume contracted and hypokalemic (VCHK) by dietary restriction. AII sensitivity was examined by determining the dose of AII required to raise the mean arterial pressure 20 mm Hg. When compared with control rats. VCHK and hypokalemic rats were significantly less sensitive to AII. VCHK rats were significantly less sensitive to AII than hypokalemic rats. Both experimental groups were similarly hypokalemic, but plasma renin activity (PRA) of VCHK only was greater than control values. In VCHK rats, acute K+ restoration partially corrected AII hyporesponsiveness, although plasma K+ increased to normal. In VCHK rats, acute volume expansion with normal saline similarly achieved only partial correction of AII hyporesponsiveness although PRA values fell to the control range. Simultaneous K+ restoration and volume expansion to VCHK rats successfully restored AII sensitivity to the control range. Dietary sodium, chloride, and potassium restriction did not increase urinary excretion to PGE2. Indomethacin (5 mg/kg, iv) given acutely to VCHK rats did not significantly after baseline hyporesponsiveness to AII. Norepinephrine vascular sensitivity was not affected by either volume contraction or hypokalemia. These data demonstrate that volume contraction and hypokalemia individually depress exogenous AII sensitivity in the rat and do so by separate and additive mechanisms. Furthermore, these mechanisms appear to be independent of PG.
Oxygen-induced contraction in the guinea pig neonatal ductus arteriosus.
Authors: Roulet M J , Coburn R F
Published: June 2012

We investigated the mechanism of oxygen-induced contractions in ductus arteriosus isolated from neonatal guinea pig. A preparation equilibrated at low Po2 (less than 40 mm Hg) displayed a steady membrane potential of -54.8 mV. Application of oxygen (Po2 (less than approximately or equal to 300 mm Hg) resulted in: (1) stepwise development of tension coupled to action potentials and (2) sustained membrane depolarization to -32.9 mV associated with tonic contraction. Mechanical sensitivity to oxygen persisted at any[K]o up to 126 mM, and tension was always larger at a given [K]o or a given membrane potential with high Po2 than with low Po2. The change in membrane potential per decade change in [K]o was 35 mV at low Po2 and 16 mV at high Po2. Oxygen contractions occurred when the ductal strips were bathed in K-free media or exposed to ouabain. We conclude that oxygen caused a conductance change in the sarcolemma resulting in depolarization, which is coupled to contraction. There is also evidence of a membrane potential-independent contraction mechanism.
The effects of hypoproteinemia on blood-to-lymph fluid transport in sheep lung.
Authors: Kramer G C , Harms B A , Gunther R A , Renkin E M , Demling R H
Published: June 2012

We studied the effects of reducing the plasma protein concentration on flow and composition of pulmonary lymph in 12 unanesthetized sheep. Whole blood was removed while red cells were returned and lactated Ringers was infused at a rate sufficient to maintain pulmonary vascular pressures at baseline values. A 44-54% reduction in plasma protein concentration resulted in a decrease in the plasma oncotic pressure from 18.6 +/- 1.1 to 7.8 +/- 0.9 mm Hg. Within an hour after plasmapheresis, lymph flows increased to a maximum of 4 times baseline. Subsequently, lymph flow gradually decreased and were close to baseline at 24 hours. The plasma-to-lymph oncotic gradient was reestablished in 5 hours due to decreased lymph protein. Maintained elevation of lymph flow with hydrostatic and oncotic gradients at baseline values suggest that the blood-to-lymph barrier offers less resistance to fluid transport. The calculated filtration coefficient increased 2- to 3-fold after plasmapheresis. Protein clearances remained normally coupled to lymph flows. Thus the enhanced fluid transport cannot be attributed to a permeability change in the large pore pathways. Hypoproteinemia may alter the interstitial gel so that there is less resistance to fluid movement. Such changes in fluid conductivity between blood capillaries and lymphatics may augment the lymphatic safety factor against pulmonary edema during hypoproteinemia.
Stimulation of Sympathetic Centers by Histamine
Authors: TRENDELENBURG U.
Published: June 2012

Contraction of the nictitating membrane of the cat following intravenous injections of histamine persisted after adrenalectomy when cocaine had been injected. Since histamine has no direct effect on the nictitating membrane and since its action on the Superior cervical ganglion is abolished by cocaine, the effect seemed to be due to an action of histamine in the central nervous system. Proof has been obtained that it has such an action. In addition, injections of small doses of histamine into the ventricles of the cat's brain have been found to cause a rise of systemic blood pressure which was of central origin.
Spatial Vectorcardiograms in Normal Dogs
Authors: HORAN LEO , BURCH G. E. , CRONVICH J. A.
Published: June 2012

The spatial vectoreardiogram was recorded on 34 normal mongrel dogs employing the equilateral tetrahedral reference system. The QRS sÊ-loop was long, narrow, and elliptical, and oriented slightly to the left, ventrad and caudad, the majority of the maximal vectors lying in the fifth sextant of the triaxial reference system in both the anterior and left sagittal plane projections. The trace was inscribed in a counterclockwise direction in the frontal and left sagittal plane projections for most of the dogs. The P and T sÊ-loops were essentially of the same configuration and had the same spatial orientation as the QRS sÊ-loops, except that T sÊ-loops were often oriented in the second sextant of the triaxial reference system in both the frontal and left sagittal plane projections.
Prolonged Pressor Effects of Selective Stimulation of the Stellate Ganglion
Authors: ROHSE WAYNE G. , KAYE MICHAEL , RANDALL WALTER C.
Published: June 2012

With both intensity and duration of individual current pulses maintained constant and at low values, frequencies were varied from ½ to 80/sec., and the stimulating current was applied to the stellate ganglion of the open chest dog. Whereas systolic and pulse pressures increased rapidly with the application of high frequency currents, the pressures were not long maintained even though the stimulation was continuous. With low frequency currents, systolic and pulse pressures rose more slowly but to higher levels which were sustained for periods of 5 to 11 hours. It is believed that neither cardiac acceleration nor systemic vasoconstriction contributed significantly to the pressor responses, but rather that augmentation of myocardial contraction and increased systolic ejection were the important causative factors.
Deposition of Lipid in Calf Aorta Maintained in Vitro
Authors: STRONG JACK P. , McGILL HENRY C. , NYMAN MELVIN A.
Published: June 2012

Morphologic and histochemical observations on the isolated perfused calf aorta maintained in vitro provide evidence that the aortas remain viable during perfusion. The appearance of lipid in the inner layers of the aortic wall corresponds to the previously reported biosynthesis of lipid by the aortic wall. There is a lag period of 24 to 48 hours between the chemical and morphologic appearance of lipid.
Effect of Lung Denervation on Pulmonary Hypertension and Edema
Authors: FERGUSON DONALD J. , BERKS ERNEST M. , Frykman Robert W. , Ognanovich John
Published: June 2012

Under conditions of high pulmonary artery pressure and flow produced in dogs by a controlled systemic artery shunt, pulmonary edema occurred after denervation of the lung at arterial pressures that were tolerated without edema before denervation. Left atrial pressures were not altered by the shunt, which involved only one segment of lung. Observation of animals with shunts for 1½ to 10 months showed that denervation apparently did not affect the incidence of arteriosclerosis.
Defibrillatory Effects of Low Sodium Solutions on Ventricular Fibrillation in Isolated Hearts of Rabbits
Authors: GRUMBACH LEONARD , Wimbert J. , Pierson A. K.
Published: June 2012

Isolated hearts in ventricular fibrillation can be defibrillated without interfering with the conduction of normal impulses arriving from the atria by the perfusion of solutions containing only about half of the normal sodium content. Reversion to a sinus rhythm occurs without a pause. The action of these solutions, which closely resembles that of normal solutions containing an excess of KCl or procaine, supports the hypothesis that these agents defibrillate by interfering with the entrance of sodium ions in the rising phase of the action potential. Defibrillation by this mechanism would be possible if ventricular fibrillation were the result of the discharge of premature impulses having a low safety factor of propagation from one or more ectopic foci.
Absence of Vasoactive and Cardiotropic Substances in Coronary Sinus Blood of Dogs
Authors: JELLIFFE R. W. , WOLF C. R. , BERNE R. M. , ECKSTEIN R. W.
Published: June 2012

Elucidation of the mechanism by which coronary flow is regulated has been attempted. Substances with coronary vasodilator or vasoconstrictor properties as well as those with inotropic or chronotropic effects on isolated frog hearts were sought in the coronary sinus blood of dogs. Blood draining normal, hypoxic or "overperfused" hearts was oxygenated in a dog lung or on a screen and perfused at a controlled pressure through a rotameter into a test coronary artery of the same or second dog; unoxygenated sinus blood was also perfused into an isolated beating frog heart connected to record heart rate and amplitude of contraction. No significant differences in flow rates were observed when the test artery was perfused with oxygenated coronary sinus blood as compared to flows metered during perfusion of the artery with arterial blood. Similarly, perfusion of unoxygenated coronary sinus blood into the isolated frog heart did not affect the rate or amplitude of contraction recorded during perfusion of the heart with arterial blood. These experiments, therefore, failed to demonstrate substances having vasoactive, inotropic, or chronotropic properties in the blood draining normal, hypoxic or "overperfused" dog hearts.
Cardiovascular Response of the Anesthetized Hamster to Reserpine and Ganglionic Blockade
Authors: MAXWELL ROBERT A. , Ross SAMUEL D. , PLUMMER ALBERT J.
Published: June 2012

The changes produced by reserpine and the ganglionic blocking agent, chlorisondamine chloride on the blood pressure, peripheral flow and blood vessel caliber of the hamster have been studied in an attempt to determine the first cause of the hypotensive effect of these compounds.
Activity of the Vasomotor Centers
Authors: JONES J. J. , MCDOWALL R. J. S.
Published: June 2012

The hind limb of the cat connected to the body by its nerves alone, and perfused with Krebs' solution is a simple method of studying the reactions of the vasomotor mechanisms. The central action of epinephrine and a failure of the center as a result of prolonged hemorrhage or anoxia have been shown.
Effect of Exercise on Blood Coagulation Time and Atherosclerosis of Cholesterol-Fed Cockerels
Authors: WARNOCK NELTA HYDER , CLARKSON THOMAS B. , STEVENSON RICHARD
Published: June 2012

In cholesterol-fed cockerels, brisk walking was found to exert a favorable effect on atherogenesis. In addition, exercise significantly lengthened blood coagulation times and increased body weight gains. Vascular and hepatic cholesterol concentrations were significantly lower in exercised than in nonexercised controls. Biochemical evidence is presented indicating a greater susceptibility of the brachiocephalic arteries to atherosclerosis than the other arteries examined.
Systolic and Diastolic Pressure Relationships in the Isolated Rat Heart
Authors: FOWLER NOBLE O. , BLOOM WALTER L. , FERRIS EUGENE B.
Published: June 2012

This report deals with variations in intraventricular pressure in the excised, beating rat heart. A negative early diastolic pressure developed, the magnitude of which correlated with the vigor of contraction.
Susceptibility of the Ovariectomized Hen to Cholesterol-Induced Coronary Atherogenesis
Authors: PICK RUTH , STAMLER JEREMIAH , KATZ LOUIS N. , Johnson Philip , Friedman Dolores
Published: June 2012

A marked sex-difference in susceptibility to cholesterol-induced coronary atherosclerosis exists in mature, gonadally active birds--hens being protected against coronary involvement. This report concerns whether this protection is lost when hens are castrated.
Relation Between Coronary Sinus Plasma Potassium and Cardiac Arrhythmia
Authors: CHERBAKOFF ABRAHAM , TOYAMA SEIICHI , HAMILTON W. F.
Published: June 2012

Infusion of insulin glucose which reduces the level of potassium in the coronary sinus blood will prolong the life of dogs after coronary ligation.
An Improved Method for the Calibration of Continuously Recorded Dye Dilution Curves
Authors: EMANUEL RICHARD W. , LACY WILLIAM W. , NEWMAN ELLIOT V.
Published: June 2012

A simplified method is described for the calibration of continuously recorded dye dilution curves. The accuracy of this method is demonstrated in vitro and in vivo.
Pharmacologic Aspects of Synthetic Angiotonin
Authors: PAGE IRVINE H. , McCUBBIN J. W. , SCHWARZ HANS , BUMPUS F. MERLIN
Published: June 2012

The synthetic octapeptide angiotonin evoked systolic and diastolic pressure responses in anesthetized and unanesthetized dogs identical with those due to a natural, largely decapeptide, angiotonin, and responses to both angiotonins were modified in the same manner by a variety of procedures. Infusion of synthetic angiotonin caused hypertension sustained for the durations of the infusions and tachyphylaxis was not observed. Induced tachyphylaxis to a crude renin preparation was accompanied by loss of response to both synthetic and natural angiotonin but not to norepinephrine.
Oxygen Consumption and Tension of Isolated Heart Muscle During Rest and Activity Using a New Technic
Authors: WHALEN WILLIAM J.
Published: June 2012

A new method is described by which the relationship between length, tension, rate of contraction and oxygen consumption can be studied in masses of cardiac tissues weighing as little as 2 mg. (dry weight). The results presented suggest that satisfactory physiologic conditions prevail.
Hormonal Effects Upon in vitro Cholesterol Synthesis
Authors: NOBLE NANCY L. , BOUCEK ROBERT J.
Published: June 2012

This report concerns a comparison of the rates at which labeled acetate is converted into digitonin-precipitable substance by sponge connective tissue and the liver. The effects of the gonads and the thyroid gland on the in vitro incorporation of C
14
-labeled acetate as cholesterol were also explored.
Effect of Venous Flow on Frequency of Venous Vasomotion in the Bat Wing
Authors: WIEDEMAN MARY P.
Published: June 2012

Investigations indicated that an elevation in venous flow caused an increase in the frequency of rhythmic contractions of the small veins in the bat wing.
Production of Coronary Heart Disease in the Rabbit by Lanolin Feeding
Authors: DONOMAE IMASATO , MATSUMOTO YOSHIJIRO , KOKUBU TATSUO , KOIDE REIZO
Published: June 2012

This paper reports the production of severe coronary atherosclerosis and frequent myocardial lesions, including infarction, in rabbits by lanolin feeding and by lanolin feeding combined with other manipulations--castration, supplementary salt in the diet, ammonium chloride acidosis, nicotine and allylamine administration.
The effects of peripheral impedance and inotropic state on the power output of the left ventricle in dogs.
Authors: Sdougos H P , Schultz D L , Tan L B , Bergel D H , Rajagopalan B , Lee G de J
Published: June 2012

The power output of the left ventricle as measured by the product of the Fourier components of aortic pressure and aortic flow is linked by definition to the arterial impedance facing the heart as measured by the quotient of these components. Consequently, the use of power measurements to assess ventricular performance can be ambiguous when accompanied by afterload changes. The heart is considered to function normally between two extremes, a constant flow pump, and a constant constant pressure pump, and two power limits are defined from these. The power limits describe the extent to which impedance changes can affect the power delivered by the left ventricle. Measured power changes that are found to lie outside the two limits can be unambiguously ascribed to changes in inotropic state. The results from preliminary dog experiments designed to test this method are reported. Cardiac sympathetic stimulation and isoprenaline infusion were used to provide a pure inotropic stimulus and a mixture of inotropic and afterload changes, respectively. The technique was able to detect inotropic changes in the heart even in the presence of simultaneous changes in afterload. Eight conventional indices of cardiac performance were monitored for comparison. The extent of their afterload dependence may not be as easily quantified.
Interaction of adriamycin in vitro with cardiac myofibrillar proteins.
Authors: Lewis W , Kleinerman J , Puszkin S
Published: June 2012

Binding of the anthracycline antibiotic doxorubicin [Adriamycin (ADR)] to selected cardiac muscle contractile proteins was determined in purified canine heart actin and alpha-actinin. Adriamycin binding to these proteins in solution was measured by equilibrium dialysis and gel filtration with [14C]-labeled ADR. Adriamycin did not bind when its primary amino group was blocked. Adriamycin binding did not affect actin polymerization as detected by viscometry. Viewed under the electron microscope, however, ADR promoted formation of distinct actin filaments in the presence of microM amounts of ATP without K+ and MG++. Adriamycin-induced actin microfilaments were thicker (120 A) than those of F-actin controls (70 A) and stimulated myosin-ATPase to higher levels than the F-actin controls. It appears that ADR has a direct effect on the biophysical and biochemical properties of heart myofibril proteins in vitro.
Left ventricular dynamic geometry in the intact and open chest dog.
Authors: Walley K R , Grover M , Raff G L , Benge J W , Hannaford B , Glantz S A
Published: June 2012

No approach to describing the heart's dynamic geometry has been widely adopted, probably because all require questionable assumptions of chamber shape, symmetry, or placement of the measuring devices. In other words, these approaches require assumptions about shape to reach conclusions about shape. We present an analysis that avoids such assumptions and provides an objective description of how the left ventricle deforms and rotates during the cardiac cycle. We only assume that the deformation of the left ventricular cavity is homogeneous, and explicitly validate this assumption. Our analysis yields the following new information about the contracting left ventricle: three principal directions of deformation and the relative length change alone these directions: the axis and angle of rotation, and relative volume. All these changes are referenced to the ventricle's configuration at end-diastole. We instrumented 13 dogs with tantalum screws without opening their chests. During systole, the three principal directions of deformation essentially are aligned along apex-base, anterior-posterior, and septum-free wall directions. There is little length change in the apex-base direction. The anterior and septal principal directions do not remain fixed with respect to the heart's anatomy during systole. During isovolumic relaxation and early filling, systolic shape changes are reversed. During slow filling, only small shape changes occur. Opening the pleura or performing a sternotomy and pericardiectomy makes the heart change orientation within the chest, but does not alter the magnitude of shortening, relative to the left ventricle's end-diastolic configuration.
Accelerated repletion of ATP and GTP pools in postischemic canine myocardium using a precursor of purine de novo synthesis.
Authors: Swain J L , Hines J J , Sabina R L , Holmes E W
Published: June 2012

During ischemia, the myocardial content of the purine nucleotides ATP and GTP falls and remains depressed for hours to days. Prolonged depletion of ATP in the postischemic state is accompanied by functional and ultrastructural abnormalities. This report describes the successful use of the purine precursor 5-aminoimidazole-4-carboxamide riboside to selectively enhance the rate of repletion of the ATP and GTP pools in postischemic myocardium.
Carotid sinus baroreceptor reflex control and epinephrine. Influence on capacitive and resistive properties of the total pulmonary vascular bed of the dog.
Authors: Shoukas A A
Published: June 2012

To quantify the importance of the carotid sinus baroreceptor reflex and the interaction with epinephrine infusion on total pulmonary vascular capacity and resistance, I have simultaneously measured total pulmonary vascular compliance, changes in pulmonary blood volumes, and changes in resistances in seven sodium pentobarbital-anesthetized dogs. A preparation was used that bypasses the right and left hearts allowing for the simultaneous measurement of the pulmonary as well as the systemic vascular bed parameters. At intrasinus pressures of 50, 125, and 200 mm Hg, without epinephrine infusion, the pulmonary vascular resistance was 0.134, 0.121, and 0.109 mm Hg/(ml per min per kg) and the systemic vascular resistance was 1.21, 0.87, and 0.63 mm Hg/(ml per min per kg). Epinephrine infusion of 1 microgram/min per kg at each intrasinus pressure caused the resistances of both vascular beds to increase. Pulmonary vascular resistance increased to 0.157 mm Hg/(ml per min per kg) and showed no further changes with changes in ISP. However, systemic vascular resistance did decrease from 1.49 to 1.41 and 1.25 at intrasinus pressures of 50, 125, and 200 mm Hg. During control runs, pulmonary vascular capacity changed 1.06 ml/kg and systemic capacity changed 7.63 ml/kg for SP changes between 50 and 200 mm Hg. Both responses were greatly attenuated after epinephrine infusion and amounted to only 0.17 ml/kg for the pulmonary and vascular bed and 2.26 ml/kg for the systemic vascular bed. The differences in capacity changes between control and epinephrine runs for the two vascular beds were nearly equal to the change in capacities brought about by epinephrine when it was infused at a fixed intrasinus pressure of 125 mm Hg. The pulmonary vascular compliance during the control runs increased from 0.303 to 0.329 ml/mm Hg per kg when ISP was increased from 50 to 200 mm Hg. After epinephrine infusion, the pulmonary compliance was 0.273 ml/mm Hg per kg and showed no changes with intrasinus pressure. Similar results were obtained for the systemic vascular compliance which was 2.07 ml/mm Hg per kg at an ISP of 50 mm Hg and increased to 2.39 ml/mm Hg per kg to an ISP of 200 mm Hg during control runs. After epinephrine infusion, the systemic compliance was 1.89 ml/mm Hg per kg and again showed no changes with ISP. These data indicate that the baroreceptor reflex can exert control of pulmonary and systemic vascular resistance and capacitance and epinephrine can greatly attenuate the reflex control of both vascular beds.
Inosine: a protective agent in an organ culture model of myocardial ischemia.
Authors: Goldhaber S Z , Pohost G M , Kloner R A , Andrews E , Newell J B , Ingwall J S
Published: June 2012

Fetal mouse hearts in organ culture provide a model of ischemic-like injury in which the myocardial protective effect of pharmacological agents can be studied independent of blood flow. To investigate the potential protective effect of a diffusable purine under ischemic-like conditions, we used 4 mM inosine in fetal mouse heart organ cultures deprived of oxygen and oxidizable substrates for 1-10 hours. We studied hearts (n = 258) immediately after simulated ischemia (early) and after a 20-hour recovery period (late), by utilizing three indices of myocardial viability. Thallium-201 accumulation is an early marker of myocardial viability during injury, whereas the percentage of lactic dehydrogenase release from hearts to culture medium and the percentage of irreversibly injured myocytes assessed by planimetry of midventricular histological sections are late markers, used after recovery from injury. At 10 hours of injury, thallium-201 accumulation was 38% greater in inosine-supplied hearts, 3.50 +/- 0.16 vs. 2.54 +/- 0.08 (counts/min per mg wet weight)/(counts/min per microliter medium) (mean +/- SEM) (P less than 0.001). After recovery from 10 hours of injury, lactic dehydrogenase release was 29% less in inosine-supplied hearts, 35 +/- 3% vs. 49 +/- 3% (P less than 0.001). After recovery from 8 hours of injury, the percentage of histologically irreversibly injured tissue was 23% less in inosine-supplied hearts, 60 +/- 7% vs. 78 +/- 3% (P less than 0.05). These data indicate that inosine has a protective effect on fetal mouse myocardium during simulated ischemia and suggest that inosine deserves further evaluation.
The release of endogenous norepinephrine from the coccygeal artery of spontaneously hypertensive and Wistar-Kyoto rats.
Authors: Galloway M P , Westfall T C
Published: June 2012

The potassium (K+)-induced release of endogenous norepinephrine from the coccygeal artery of spontaneously hypertensive rats has been studied as a function of the development of hypertension. The absolute amount of norepinephrine released by potassium was greater in spontaneously hypertensive rat than the normotensive Wistar-Kyoto rat, regardless of age or blood pressure. However, the %-fractional release was elevated only in the rats with chronic hypertension. Preincubation of tissues with the alpha 2-antagonist, yohimbine, significantly enhanced norepinephrine overflow in all tissues studied. Young hypertensive animals demonstrated an enhancement equal to the Wistar-Kyoto rat controls. In the adult spontaneously hypertensive rat, however, there was a significantly lesser enhancement produced by yohimbine. Levels of norepinephrine in the nerves supplying the artery were greater in the prehypertensive spontaneously hypertensive rat than the age-matched Wistar-Kyoto rat. The norepinephrine content in arteries from adult animals was equivalent. The explanation for the attenuation of the yohimbine effect of chronic hypertensive animals is unclear. Although several explanations are possible, the data are consistent with the hypothesis that spontaneously hypertensive rats with chronic hypertension have subsensitive prejunctional alpha 2-receptors as evidenced by an increased %-fractional release of norepinephrine and a decreased enhancement of overflow in the presence of yohimbine. Clearly, further studies are needed to answer this provocative question and to understand the complex interactions of adrenergic neurotransmission in hypertensive animals.
Electrophysiology of the normal-to-hypoxic transition zone.
Authors: Bukauskas F
Published: June 2012

The "normal-to-hypoxic" transition zone was modeled after the chamber technique for perpendicular and parallel orientation with respect to the direction of fiber axis. The evidence obtained from the recording of the transmembrane action potentials suggests the presence of a preservation phenomenon in the hypoxic area, based on the utilization of energy stores of the normoxic area. Better intercellular coupling in longitudinal than in transverse fiber direction results in the anisotropic properties of the preservation phenomenon. The preservation phenomenon provides a basis for the existence of critical size of the viable hypoxic area compared to the size of the transitional zone. The crucial role of electrotonic coupling was demonstrated, as well as the possible contribution to the preservation phenomenon mechanism of the cell-to-cell diffusion of metabolites.
Regulation of phosphorylase kinase in rat ventricular myocardium. Role of calmodulin.
Authors: Werth D K , Hathaway D R , Watanabe A M
Published: June 2012

Conversion of phosphorylase b to a which is catalyzed by the enzyme phosphorylase kinase is known to require Ca++. Trifluoperazine, an inhibitor of calmodulin-dependent enzymes, was utilized in the present study to clarify the role in vivo of calcium-calmodulin regulation of phosphorylase kinase. Twenty-minute preperfusion of isolated rat ventricles with 10(-5) M trifluoperazine had no effect on basal levels of phosphorylase a but significantly attenuated phosphorylase activation induced by either calcium (3.75 mM) or isoproterenol (3 x 10(-9) M, 3 x 10(-8) M). The positive inotropic effect of both agents and cyclic adenosine 3',5'-monophosphate (cAMP) levels were not altered by trifluoperazine in the perfused hearts. In addition, no effects of 10(-5) M trifluoperazine were noted on beta-adrenergic receptor binding of [3H](+/-)carazolol or on adenylate cyclase activity. In vitro studies with partially purified rat cardiac phosphorylase kinase demonstrated 1.5- to 3-fold stimulation by exogenous calmodulin. The addition of 10(-5) M trifluoperazine prevented calmodulin stimulation but had little effect on activity in the absence of exogenous calmodulin. The present results suggest that reversible binding of calcium-calmodulin may represent a physiological means for regulating phosphorylase kinase activity in rat cardiac muscle.
Amrinone activates K+-depolarized atrial and ventricular myocardium of guinea pigs.
Authors: Adams H R , Rhody J , Sutko J L
Published: June 2012

Amrinone is a new synthetic drug that increases contractile strength of mammalian heart muscle; however, its mechanism of positive inotropic action has not been determined. We now report that amrinone (0.053-5.3 mM) consistently restores typical slow response electromechanical activity fo K+-depolarized atrial and ventricular myocardial preparations from guniea pigs. This action was blocked in both tissues by D-600 (1 microM), but it was not significantly inhibited by either tetrodotoxin (23.5 microM), d,l-propranolol (1 microM), or phentolamine (10 microM). Cimetidine (3 microM) or metiamide (10 microM) slightly inhibited amrinone's effect only in the ventricle, whereas pyrilamine (10 microM) slightly inhibited amrinone's response only in the atrium. These data indicate that amrinone's positive inotropic action may involve augmented Ca++ influx via the slow inward Ca++ current, and that although this action is independent of adrenoceptor mechanisms, it seems to include a small histaminergic component.
Transmural cellular damage and blood flow distribution in early ischemia in pig hearts.
Authors: Fujiwara H , Ashraf M , Sato S , Millard R W
Published: June 2012

Transmural histological changes were determined morphometrically in the left ventricular free wall of 20 pigs after ligation of distal left anterior descending coronary artery for 10, 20, 40, and 120 minutes. Hemodynamics were recorded and regional blood flow distribution was measured in the ischemic zone. Coronary occlusion produced regional transmural ischemia without producing significant systemic hemodynamic change. The microsphere blood flow technique revealed that blood flow was less than 0.05 ml/min per g in all layers of the ischemic zone, i.e., inner, middle, and outer thirds. Ischemic cellular damage was classified and quantified from grade 0 to grade 5 (0 being normal and 5 being the most severe damage) with light microscopy and confirmed by electron microscopy. Layers of 200 micrometers immediately beneath the endocardium and epicardium showed minimal ischemic damage of less than grade 1.4 regardless of duration of ischemia in all hearts. In the ischemic left ventricular wall, except for the above layers, a definite transmural gradient of the cellular damage existed from the inner third (grade 2.3 +/- 0.1) to the outer third (grade 1.3 +/- 0.2) at 20 minutes of ischemia and at 40 minutes of ischemia (grades 3.6 +/- 0.1 and 1.9 +/- 0.3, respectively). The transmural ischemic damage gradient disappeared at 120 minutes of ischemia, where the inner and outer third ischemic grades were both 5.0 +/- 0.1. The data suggest that the limited ischemic damage which occurs in the few cell layers beneath endocardium and epicardium may be explained by regional collateral blood flow. An early ischemic damage wavefront phenomenon does exist in the pig myocardium and is independent of myocardial blood flow and its distribution. The transmural cell damage gradient may be the result of transmural gradients of wall stress and intramyocardial pressure in vivo. Therefore, it appears that factors other than blood flow are the major determinants of ischemic cellular damage in the left ventricular wall of hearts lacking a collateral blood supply.