bluuebunny/crossref_metadata_2025 huggingface dataset:
Nicardipine prevents calcium loading and "oxygen paradox" in anoxic single rat myocytes by a mechanism independent of calcium channel blockade.
Authors: Hano O , Silverman H S , Blank P S , Mellits E D , Baumgardner R , Lakatta E G , Stern M D
Published: June 2012

The protective effect of nicardipine (1 and 4 microM) against reoxygenation injury was studied in an unstimulated rat single myocyte oxygen paradox model in comparison with control (no drug) or nifedipine (1 microM). Either concentration of nicardipine was strongly protective, approximately doubling the duration of ATP depletion (rigor) that cells could withstand without undergoing hypercontracture when reoxygenated. Nifedipine (1 microM), which matched the negative inotropic effect of nicardipine (4 microM) (as measured by extent of shortening when stimulated), had no protective effect against reoxygenation injury. Neither drug affected the time to rigor, which is a measure of the rate at which the resting cell consumes its endogenous glycogen stores during anaerobic metabolism. Intracellular calcium, measured with the fluorescent probe indo-1, which partitions into both cytosol and mitochondria, rose progressively throughout the rigor period. This rise in calcium was almost totally suppressed by nicardipine (1 microM) but was unaffected by nifedipine. We conclude that nicardipine possesses a direct protective effect on the myocardium not shared by all dihydropyridines. This effect is associated with the prevention of intracellular, and probably mitochondrial, calcium loading but is probably not due to blockade of the L-type calcium channel or reduction of metabolic rate.
Control of the Na-Ca exchanger in isolated heart cells. II. Beat-dependent activation in normal cells by intracellular calcium.
Authors: Haworth R A , Goknur A B
Published: June 2012

Electrical stimulation of isolated adult rat heart cells in suspension at 4 Hz resulted in a fourfold increase in the rate of sodium influx and efflux across the sarcolemma, with no change in total cell sodium, as measured with 22Na. The magnitude of stimulation-dependent sodium fluxes under these conditions averaged 17 nmol/min/mg protein. The increased rate of efflux was inhibited by tetrodotoxin, verapamil, or dichlorobenzamil and required extracellular calcium. The inhibition by tetrodotoxin was overcome by Bay K 8644. The basal rate of 22Na efflux in cells at rest was inhibited only slightly by dichlorobenzamil. The stimulation-induced efflux was not inhibited by ouabain, but in the presence of ouabain, stimulation increased the rate of accumulation of total sodium by 4 nmol/min/mg. This increase was inhibited by tetrodotoxin or verapamil. A calcium-dependent increase in rate of 22Na influx and efflux could also be induced by KCl addition. This was inhibited by verapamil and dichlorobenzamil but not by tetrodotoxin and was reversed by EGTA, but only after a delay. We conclude the following. 1) The Na-Ca exchanger in cells at rest is no more than 10% activated. 2) The exchanger becomes activated directly or indirectly by calcium that enters the cell through calcium channels during excitation. 3) In this preparation the major part of excitation-induced sodium fluxes are mediated by the Na-Ca exchanger, with only a relatively small direct participation of sodium channels. These channels participate indirectly by promoting calcium channel activation. 4) If all the calcium-dependent sodium fluxes were Na-Ca exchange, then calcium flux through the exchanger per beat would be about sevenfold larger than that through the calcium channels. An undetermined part of the calcium-dependent sodium fluxes, however, could be a direct Na-Na exchange through the activated Na-Ca exchanger.
Beta-adrenergic receptor-G protein-adenylate cyclase complex in experimental canine congestive heart failure produced by rapid ventricular pacing.
Authors: Marzo K P , Frey M J , Wilson J R , Liang B T , Manning D R , Lanoce V , Molinoff P B
Published: June 2012

Changes in the beta-adrenergic receptor-G protein-adenylate cyclase complex were investigated in an experimental canine model of low-output heart failure produced by chronic rapid ventricular pacing. The contractile response occurring after exposure to the beta-adrenergic agonist dobutamine, measured as peak left ventricular + dP/dt, was decreased after 3 weeks of pacing. To further characterize the diminished functional responsiveness to beta-adrenergic receptor stimulation, beta-adrenergic receptor-adenylate cyclase coupling was investigated using membranes prepared from both control and paced animals. The density of beta-adrenergic receptors was decreased by 40% with a selective downregulation of the beta 1-subtype. The affinity of the receptor for the antagonist radioligand [125I]iodocyanopindolol remained unchanged. A defect in coupling was suggested by a decreased ability of isoproterenol, fluoride, and forskolin to stimulate adenylate cyclase in membranes prepared from failing hearts. Determination of the levels of Gi alpha (the alpha-subunit of Gi) by immunoblotting and pertussis toxin labeling revealed modest increases of approximately 30%. Furthermore, Mn2+ and purified Gs failed to stimulate adenylate cyclase in membranes prepared from failing hearts, indicating an impairment in the catalytic moiety of adenylate cyclase itself or in the ability of adenylate cyclase to couple to Gs. In contrast, complementation assay did not reveal differences in the functional activity of Gs alpha (the alpha-subunit of Gs). Taken together, these data demonstrate a selective decrease in the beta 1-subtype of adrenergic receptors and an increase in a 40-kd G1-like protein in the failing heart. Similar changes have been described in human idiopathic dilated cardiomyopathy. In addition to these changes, we identified a possible defect at the level of the catalytic subunit of adenylate cyclase.
Nucleotide precursors modify the effects of isoproterenol. Studies on heart function and cardiac adenine nucleotide content in intact rats.
Authors: Zimmer H G , Schneider A
Published: June 2012

In closed-chest rats, isoproterenol (ISO, 25 mg/kg), 5 hours after subcutaneous administration, increased heart rate by 53%, left ventricular (LV) dP/dtmax by 80%, and cardiac output by 37%. LV systolic pressure (LVSP, -10%), mean arterial pressure (MAP, -12%), and total peripheral resistance (TPR, -36%) were diminished. In separate experiments, continuous intravenous infusion of adenine (50 mg/kg/hr) for 5 hours reduced heart rate (-11%), LVSP (-16%), MAP (-20%), TPR (-33%), and LV dP/dtmax (-20%). Cardiac output was increased (+20%). Inosine has been shown to have similar effects, except for a decline in cardiac output. Adenine (50 mg/kg/hr) attenuated the ISO-induced increase in heart rate and LV dP/dtmax and aggravated the decline in LVSP, MAP, and TPR. The increase in cardiac output was not changed. Inosine (200 mg/kg/hr) modified the ISO effects to a similar extent. Ribose (200 mg/kg/hr) added to the adenine infusion did not have functional effects. However, it aggravated the modifying influence of inosine on LVSP, LV dP/dtmax, and MAP. ISO reduced the cardiac ATP content (mumol/g) from a control value of 5.02 +/- 0.06 (n = 12) to 3.51 +/- 0.13 (n = 10). Adenine (3.56 +/- 0.21, n = 7) and ribose (3.64 +/- 0.11, n = 9) alone did not affect it, but inosine attenuated it (4.33 +/- 0.08, n = 8). Adenine and inosine in combination with ribose abolished the ISO-induced ATP decline (5.18 +/- 0.23, n = 7, and 4.76 +/- 0.10, n = 8, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of purines and pyrimidines on the rat mesenteric arterial bed.
Authors: Ralevic V , Burnstock G
Published: June 2012

The effects of the purines, adenosine 5'-triphosphate (ATP) and guanosine 5'-triphosphate (GTP), and the pyrimidines, uridine 5'-triphosphate (UTP), cytidine 5'-triphosphate (CTP), and thymidine 5'-triphosphate (TTP), on vascular resistance were investigated in the rat mesenteric arterial bed. In preparations at basal tone, these agents produced dose-related vasoconstriction with a potency order of ATP greater than CTP greater than UTP much greater than TTP = GTP. When tone was raised with norepinephrine (30 microM), these agents caused dose-related vasodilatation with the potency order of UTP = ATP greater than TTP = GTP. CTP did not elicit vasodilatation. Removal of the endothelium with sodium deoxycholate resulted in an increased responsiveness of the mesenteric bed preparation to the vasoconstrictor effects of each of the purines and pyrimidines tested. The selective P2 X-purinoceptor-desensitizing agent alpha,beta-methylene ATP inhibited vasoconstrictor responses to ATP and to CTP but had no effect on vasoconstrictor responses elicited by UTP, TTP, and GTP. In raised-tone preparations, vasodilator responses to ATP, UTP, TTP, and GTP were abolished after removal of the endothelium with sodium deoxycholate. Responses to acetylcholine were also abolished; those to sodium nitroprusside were unimpaired. An inhibitor of the formation of nitric oxide from L-arginine, N omega-nitro-L-arginine methyl ester (30 microM), which antagonizes responses mediated by endothelium-derived relaxing factor (nitric oxide), attenuated vasodilatation to ATP, UTP, and acetylcholine but not to sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)
Expression of ventricular myosin subunits in the atria of children with congenital heart malformations.
Authors: Shi Q W , Danilczyk U , Wang J X , See Y P , Williams W G , Trusler G A , Beaulieu R , Rose V , Jackowski G
Published: June 2012

The presence of ventricular myosin light chains in the atria of children with congenital heart disease was demonstrated by two-dimensional polyacrylamide gel electrophoresis, peptide mapping, and Western blot analysis. Ventricular myosin light chains were present in 27% of biopsies from 91 children with different forms of congenital heart disease. Perimembranous ventricular septal defects and tetralogy of Fallot were associated with the presence of ventricular myosin light chains in 50% of patients. The presence of ventricular myosin light chains in these atria did not correlate with pressure or volume overload. Analysis of myosin heavy chain isotype in the same biopsies by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, peptide mapping, and Western blot analysis indicated that there was no detectable expression of ventricular myosin heavy chain (beta-subunit), suggesting that the genes for the myosin heavy chains and light chains are not expressed coordinately.
The influence of cold stress on the myosin heavy chain expression of cardiac and smooth muscle in normotensive and spontaneously hypertensive female rats.
Authors: Adler K , Boels P , Ganten U , Ganten D , Morano I
Published: June 2012

Cold exposure (6 weeks at 4 degrees C) of normotensive (Wistar-Kyoto) and stroke-prone spontaneously hypertensive female rats led to cardiac hypertrophy (in stroke-prone spontaneously hypertensive rats), increased the level of plasma thyroxine, and increased the alpha-myosin heavy chain expression in the left ventricle. In contrast, myosin heavy chain expression of both main mesenteric artery and uterus was not affected by cold stress and chronic hypertension, suggesting different regulation of myosin heavy chain expression in smooth and cardiac muscle in vivo.
A Study of the Natural History of Adrenal-Regeneration Hypertension
Authors: SKELTON FLOYD R.
Published: June 2012

The natural history of adrenal-regeneration hypertension was studied over a period of 21 weeks. The blood pressure remained elevated in a high percentage of rats with severe adrenal-regeneration hypertensive disease following removal of the regenerated adrenal. Rats with less severe adrenal-regeneration hypertensive disease showed a moderate decline in blood pressure following either removal of the regenerated adrenal or substitution of water for saline drinking solution. A marked fall in blood pressure resulted when the regenerated adrenal was removed and water substituted for saline.
Elevation of Inferior Vena Cava Pressure and Thoracic Lymph and Urine Flow
Authors: KATZ YALE J. , COCKETT A. T. K. , MOOR RAYMOND.S
Published: June 2012

With an increase in renal vein pressure by partial obstruction of the inferior vena cava in dogs, there follows an increase in thoracic lymph flow and a simultaneous decrease in urine flow and urine sodium excretion per minute. The increase in lymph flow appears to be caused by an increased production of renal lymph, since control animals with absent or nonfunctioning kidneys fail to show this lymph flow increase. Renal deviation of fluid and sodium to the lymphatics may similarly occur in heart failure and account for the retention of sodium and water.
Effects of Enzyme Inhibitors on the Contractility and Membrane Potentials of the Rat Atrium
Authors: WEBB J. LEYDEN , HOLLANDER PHILIP B.
Published: June 2012

Enzyme inhibitors alter the rate of ion movement across the membrane of the rat atrial cell during the repolarization phase. There is simultaneously no constant change in the resting potential while the action potential amplitude is usually depressed to a moderate degree. The relationship between these membrane changes and the altered contractility is investigated. It is concluded that metabolic depression reduces the contractility by two mechanisms: one is a membrane effect, the result of the shortening of the action potential duration, and the other is an effect more directly on the contractile processes.
Influence of the Rate of Coronary Plasma Flow on the Extraction of Rb
86
from Coronary Blood
Authors: LOVE W. D. , BURCH G. E.
Published: June 2012

To determine whether myocardial uptake of Rb
86
can be used as a useful index of coronary plasma flow, the extraction of Rb
86
from arterial plasma during one passage through the myocardium of dogs was measured at varying rates of flow. At rates of flow which are encountered in man, changes in the rates of flow and uptake of isotope by the myocardium paralleled each other closely. Rb
86
uptake is a useful index of coronary blood flow in dogs.
The Influence of Acute Stress on the Response of Rabbits to Intravenous Endotoxin
Authors: ANDERSON JAMES M. , BRUNSON JOEL G.
Published: June 2012

Immature rabbits were subjected to an acute stress period in a modified Noble-Collip drum, alone and in conjunction with an intravenous injection of
E. coli
endotoxin. The lethal effects and incidence and severity of the morphologic changes were appreciably greater in the animals given endotoxin in association with stress than in those subjected to rotation alone.

The similarity of these lesions to those produced by two properly spaced injections of endotoxin is discussed. The results of the study support the hypothesis that adrenal gland hormones participate in the effects produced by endotoxin.
Stretch Reflexes from the Dog's Lung to the Systemic Circulation
Authors: SALISBURY PETER F. , GALLETTI PIERRE-M. , LEWIN RICHARD J. , RIEBEN P. ANDRÉ
Published: June 2012

Evidence is presented that reflex systemic vasodilatation occurs after stretching dog's lungs by either mechanical traction or positive pressure ventilation under conditions of separate pulmonary and systemic perfusion. This reflex is mediated by the vagus.
Cardiovascular Effects of Chloroquine with Special Reference to Its Antifibrillatory Action
Authors: HESS MARILYN E. , SCHMIDT CARL F.
Published: June 2012

Intravenous injections of chloroquine terminated experimental atrial fibrillation in open chest dog preparations. Chloroquine and quinidine possess equal vasodilating properties when injected intra-arterially in the same dosage. Chloroquine and quinidine were equally effective in decreasing resting excitability of isolated cat papillary muscle; conduction velocity was markedly slowed by quinidine, but only slightly decreased by chloroquine.
Comparative Reactivities of Aortic Strips from Hypertensive and Normotensive Rats to Epinephrine and Levarterenol
Authors: MALLOV SAMUEL
Published: June 2012

Rats were rendered hypertensive by two different technics. Isometric tensions developed by strips of aorta from these rats, when exposed to various concentrations of epinephrine and levarterenol, were compared with those developed by aortic strips from normotensive controls. Almost all of the aortic strips from the DCA-salt hypertensive rats responded with smaller contraction tensions to both pressor agents than did the corresponding control strips from the normotensive animals. The same was true for most of the strips obtained from the renal hypertensive rats. These results do not lend support to the hypothesis that vascular hyperreactivity is the basis of many forms of hypertension.
Effects of Testosterone and Castration on Cholesteremia and Atherogenesis in Chicks on High Fat, High Cholesterol Diets
Authors: PICK R. , STAMLER J. , RODBARD S. , KATZ L. N.
Published: June 2012

Testosterone in large doses in intact cholesterol-fed cockerels partially inhibited hypercholesteremia, without effecting aorta or coronary atherosclerosis. Castration, with and without testosterone administration in young male and female chicks, was without influence on hypercholesteremia and atherogenesis.
Influence of Prolonged Hypothermia and Hyperthermia On Myocardial Sodium, Potassium and Chloride
Authors: SPURR G. B. , BARLOW GEORGE
Published: June 2012

In dogs cooled to 25 C. and in animals maintained at this rectal temperature for 2 and 4 hours there was a progressive increase in K and decrease in Na content of the left ventricular muscle, with no change in total Cl and H
2
O. Animals heated to a rectal temperature of 41.5 C. for 1 hour exhibited an elevated total K and no change in total Na, Cl and H
2
O contents of the myocardium.
Effect of Taurine, Glycine and β-Sitosterols on Serum and Tissue Cholesterol in the Rat and Rabbit
Authors: HERRMANN ROY G.
Published: June 2012

Rats and rabbits were fed a hypercholesteremic diet until elevated serum cholesterol levels were observed in all animals. The animals were then divided into groups, one group remaining on the original diet and the others receiving the same hypercholesteremic diet fortified with either taurine, glycine, or β-sitosterols. In the rat, 4 per cent taurine in the diet significantly decreased the serum, liver, and aorta cholesterol concentration, but glycine was without significant effect. In the rabbit, 2 per cent β-sitosterol in the diet significantly reduced the serum, liver, and aorta cholesterol, while taurine or glycine produced no significant effect. Neither taurine, glycine, nor β-sitosterols produced any signs of toxicity.
Effect of Nicotine on Cholesterol-Induced Atherosclerosis in the Rabbit
Authors: WENZEL DUANE G. , TURNER JAMES A. , KISSIL DONALD
Published: June 2012

Nicotine was administered orally in three dosage levels to female rabbits fed a 1 per cent cholesterol, 5 per cent oil diet for 24 weeks. Serum cholesterol and phospholipid values and electrocardiograms, both with and without ergonovine stress, were obtained at eight week intervals. Gross and microaortic pathology and cardiac micropathology were determined at the end of the experiment. Serum cholesterol and phospholipid values and aortic atherosclerosis were not affected by the addition of nicotine. Mortality, the incidence of positive ergonovine stress tests, myocardial necrosis and fatty metamorphosis, and peripheral vascular changes were increased. A dose-response relationship could not be established for nicotine.
Coronary Circulation in Dog's Heart
Authors: PROVENZA D. VINCENT , SCHERLIS SIDNEY
Published: June 2012

A study of the capillary structure in the myocardium of the dog reveals three divergent types which can be distinguished on the basis of the presence or absence of sphincter muscle cells located in a position comparable to that occupied by the media of the larger vessels. The true
capillary
is completely wanting in muscular elements; the
precapillary
contains one or more muscle cells at the segmental area of attachment with the parent vessel; and the
metarteriole
contains one or more muscle cells located at irregular intervals along the vessel.
Flow of Liquids Through "Collapsible" Tubes
Authors: HOLT J. P.
Published: June 2012

Liquid flowing through a thin-walled "collapsible" tube similar to a vein, inclined to any angle between vertical and slightly above horizontal, differs from the flow in rigid tubes in that: a "collapsible" tube accepts any flow presented to it without affecting the rate of flow through the system; the lateral pressure at all cross sections throughout the tube is zero and does not change as the flow changes; the cross section of the tube and the mean velocity of flow increase as the flow increases; for any particular flow, the cross section increases and the mean velocity of flow diminishes as the potential energy difference between the upper and lower ends of the tube is decreased; for any given flow and potential energy difference, an increase in the length of the tube causes an increase in the cross section and a decrease in the mean velocity; also, an increase in the perimeter of the tube causes an increase in cross section and a decrease in mean velocity, and an increase in the viscosity of the liquid causes an increase in cross section and a reduction in mean velocity. In such tubes there is no lateral pressure gradient between any two cross sections as there is in rigid tubes; instead there is a
potential energy gradient
which is proportional to the energy loss along the tube. Under certain conditions the flow of liquid through a collapsible tube is described with a reasonable degree of accuracy by a modification of Poiseuille's law for tubes of elliptical cross section.
Saturated and Unsaturated Fats
Authors: STAMLER J. , PICK R. , KATZ L. N.
Published: June 2012

The effects of supplementary oils--saturated and unsaturated--were examined in groups of cholesterol-fed cockerels. Unsaturated oils failed to suppress hypercholesterolemia and atherogenesis. When various oils and fats high in oleic acid were added to the mash, slight lowering of serum cholesterol occurred. Oleic acid per se given to a group was accompanied by a diminution in atherosclerosis.
Thermal Dilution Curves in the Intact Animal
Authors: GOODYER ALLAN V. N. , HUVOS ANDREW , ECKHARDT WILLIAM F. , OSTBERG ROBERT H.
Published: June 2012

The acceptance of thermal dilution curves for the estimation of cardiac output has been discouraged by unconvincing comparisons with the Fick method and by the possibility of the loss of "indicator" to the tissues of the central circulation. The present studies were undertaken to examine the technical and physiologic factors affecting thermal curves, with particular reference to tissue heat exchanges, and to provide adequate data for estimating the usefulness of the thermal curves for simultaneous measurements of right and left ventricular outputs.
Effect of Saturated and Unsaturated Fats on the Concentration of Serum Cholesterol and Experimental Atherosclerosis
Authors: STEINER ALFRED , VARSOS ARISTIDES , SAMUEL PAUL
Published: June 2012

The feeding of a diet rich in unsaturated fats to rabbits produced no significant alteration of the serum cholesterol level, while the feeding of a diet rich in saturated fats produced an elevation of the serum cholesterol without the development of experimental atherosclerosis. The addition of unsaturated fats to a diet rich in cholesterol failed to prevent hypercholesterolemia and experimental atherosclerosis in rabbits.
Oxygen Consumption of the Thoracic Aorta of Normal and Hypercholesteremic Rats
Authors: LOOMEIJER F. J. , OSTENDORF J. P.
Published: June 2012

The respiratory activity of the thoracic aorta wall of hypercholesteremic rats was shown to be 30 to 40 per cent higher than in normal animals. The addition, in vitro, of serum of different cholesterol content did not affect the oxygen consumption.
Effect of Histamine and of the Anaphylactic Reaction on Isolated Guinea Pig Atria
Authors: PENNA MARIO , ILLANES ALEJANDRO , UBILLA MARIO , MUJICA SERGIO
Published: June 2012

Addition of specific antigen to the isolated atria of sensitized guinea pigs and of histamine to those of nonsensitized animals resulted in an increase of both frequency and amplitude of contraction and in the appearance of rhythmic activity in the isolated left atrium. On a quantitative basis the anaphylactic response looks like the effects of histamine in concentrations between 10
-3
and 10
-2
mM/L. No qualitative differences between the effects of histamine and those of the anaphylactic reaction were observed. Since isolated atria thus are seen to participate in tissue sensitization, the heart should be considered as a potential shock organ in the anaphylactic reaction.
Unipolar Potential Measurements in the Electric Field Produced by an Arbitrary Dipole in a Circular Homogeneous Lamina
Authors: BAYLEY ROBERT H.
Published: June 2012

Unipolar potential measurements are carried out on a circular homogeneous conducting lamina. One set of potential measurements is made using an averaging net work for the zero potential reference. A second set of potential measurements is made with reference to the Frank-Kay "zero" potential reference on the outside ground of the dipole generating circuit. Both sets of unipolar potential measurements are then compared with the theoretically predicted values. The first set is found to be highly accurate. The second set is found to contain errors which make this method unacceptable.
Effect of Alcohol Ingestion on Experimental Chicken Atherosclerosis
Authors: NIKKILA ESKO A. , OLLILA OIVA
Published: June 2012

The use of alcohol is common enough to be a noteworthy item in attempts to elucidate the role of external factors in atherogenesis. Because valid observations on this point are made only with difficulty in man, the effect of continuous alcohol ingestion on atherosclerosis in chickens was studied. It appeared that alcohol caused a significant elevation of the plasma cholesterol and phospholipid levels, but was without effect on aortic and coronary atherosclerosis, either spontaneous or induced.
Mechanisms of Cardiac Control in Exercise
Authors: RUSHMER ROBERT F. , SMITH ORVILLE , FRANKLIN DEAN
Published: June 2012

Left ventricular performance during spontaneous exercise has been continuously analyzed in terms of direct recordings of diameter, effective pressure and other parameters derived by electronic computors. The changes in left ventricular performance during treadmill exercise have been compared with a number of experimentally induced responses in the same intact unanesthetized dog on the same day. These direct comparisons revealed that experimentally-induced increased venous return, reduced peripheral resistance, or administration of autonomic hormones do not reproduce the spontaneous exercise response. Better reproductions of the exercise response could be achieved by careful administration of isopropyl arterenol (Isuprel), by combined administration of epinephrine or norepinephrine) and experimental tachycardia or by stimulating sympathetic nerves to the heart. Stimulation of discrete areas in the diencephalon reproduced the exercise response with remarkable accuracy without movement or evidence of distress.
Cardiac Effects of Isoproterenol, Norepinephrine and Epinephrine in Complete A-V Heart Block During Experimental Acidosis and Hyperkalemia
Authors: GUZMAN SANTIAGO V. , DELEON ANTONIO C. , WEST JAMES W. , BELLET SAMUEL
Published: June 2012

Acidosis was found to diminish the effectiveness of various sympathomimetic amines (isoproterenol, norepinephrine, and epinephrine) in increasing the idioventricular rate in dogs with experimentally induced complete A-V heart block. This diminution was correlated with the degree of acidosis (metabolic and respiratory). Hyperkalemia without significant pH change had no such effect.
Studies on the Mechanism of the Age-Related Change in Swelling Ability of Human Myocardium
Authors: KHON ROBERT R. , ROLLERSON EDWARD
Published: June 2012

Previous studies have shown that human myocardium loses its ability to swell at pH 11.2 with increasing age. This investigation indicated that the age-related difference does not exist at the subcellular level or after treatment with collagenase. Swelling did not correlate well with myofiber size or acid and base binding capacity. It was concluded that the increased rigidity with age is due to the development of a more rigid intercellular collagenous connective tissue.
Analog Computer Analysis of Flow Characteristics and Volume of the Pulmonary Vascular Bed
Authors: PARRISH DANIEL , HAYDEN DANIEL T. , GARRETT WAYNE , HUFF REX L.
Published: June 2012

Radioisotope dilution data were obtained from the pulmonary artery and pulmonary vein of catheterized dogs and an analysis for pulmonary transfer characteristics was performed with an electronic analog computer. The analog for these studies consisted of a cascade of linear delay units arranged so that both transport delay and dispersion could be independently varied. This technic makes it possible to characterize the pulmonary vascular bed without making any assumptions as to its nature. The results indicate that the dominant response of the lung is not that of a single mixing pool as suggested by Newman and others, but rather is more analogous to a laminar flow system. In addition it has been shown that an exponential extrapolation of the downslopes of the indicator dilution curves to calculate pulmonary blood volume results in a measurable error.
Intravital Staining of the Atrioventricular Bundle with Iodine Compounds during Cardiopulmonary Bypass
Authors: BITTENCOURT DELMONTE , LONG DAVID M. , LEE YUNG K. , LILLEHEI C. WALTON , THOMAS JOHNSON
Published: June 2012

Complete atrioventricular dissociation occurring as a result of intracardiac reparative surgery has been a relatively infrequent, hut serious complication. Important advances have been made in its treatment through use of isoproterenol (Isuprel) and by use of the myocardial electrode. The next obvious goal is to prevent completely, if possible, the occurrence of heart block and this depends upon an accurate and safe method of identifying the bundle at the time of cardiotomy. Solutions containing free iodine very effectively identified the conduction system at the time of cardiotomy in dogs, but produced lasting interference with cardiac conduction in most all of the animals.
Electrical and Mechanical Properties of Chick Embryo Heart Chambers
Authors: BOUCEK ROBERT J. , MURPHY WILLIAM P. , PAFF GEORGE H.
Published: June 2012

Electrical and mechanical events of the atrium, ventricle and conus of the 72-hour chick embryo heart were recorded by a specially designed instrument. The electrical-mechanical delay and the time of muscular contraction differed among the chambers, the atrium being the most rapid and the conus, the slowest. Muscular relaxation times of the atrium and ventricle were approximately one-half that of the conus. Mechanical performance, gaged by the approximations of work and power, was greatest for the ventricle, but based on the muscle mass (protein), values for the ventricle and conus were similar. Electrical activation of the ventricle followed a consistent pathway, suggesting the existence of a preferential conduction system prior to the development of the His bundle.
A Definition for Zero Potential
Authors: NELSON C. V. , GASTONGUAY P.
Published: June 2012

Equations are developed for the potential due to a source and sink, or dipole, inside a circle of finite resistivity surrounded by a two-dimensional infinite medium of different resistivity. When the resistivity of the external medium is allowed to increase to infinity, the resulting equations give identical results to those presented by Bayley for the dipole potential in an insulating circle. A method of defining the zero of potential for a bounded medium is proposed.
Influence of High Levels of Dietary Fats and Cholesterol on Atherosclerosis and Lipid Distribution in Swine
Authors: REISER RAYMOND , SORRELS MARY FRANCES , WILLIAMS MARY CARR
Published: June 2012

The degree of incorporation of injected 1-C
14
-acetate into tissue cholesterol on cholesterol free diets was much higher in the liver and plasma of swine ingesting saturated than unsaturated fat. The levels of cholesterol in all tissues increased with the presence of fat or cholesterol in the diet. In most cases, especially in the presence of cholesterol, cholesterol levels were highest in the presence of unsaturated fat. The combination of unsaturated fat with cholesterol in the diet produced the greatest degree of typical atheromatosis and the highest levels of cholesterol in the tissues, while saturated fat with cholesterol produced diffuse atypical lesions.
Effects of High Protein Intakes on Cholesterolemia and Atherogenesis in Growing and Mature Chickens Fed High-Fat, High-Cholesterol Diets
Authors: PICK R. , STAMLER J. , KATZ L. N. , CENTURY D. , JOHNSON P.
Published: June 2012

Atherogenesis can be modified by the amount of protein in the diet, both in young, growing cockerels and in mature roosters and hens on high-cholesterol, high-fat diets. Protein supplementation suppresses atherosclerosis while low-protein enhances it. Any nutritionally good protein--animal or vegetable--was found to have this effect. The hypercholesterolemia and atherosclerosis-promoting effect of butter and egg yolk could be prevented by the simultaneous feeding of large amounts of casein or egg albumen respectively. Unlike ordinary hens, oviduct-ligated hens on high-fat, high-cholesterol diets failed to exhibit intensified hypercholesterolemia and atheroselerosis on the low-protein ration.
Monophasic Curve Analysis and the Ventricular Gradient in the Electrogram of Strips of Turtle Ventricle
Authors: GARDBERG MANUEL , ROSEN IRVING L.
Published: June 2012

Experiments were performed to test the validity of representing the bipolar electrogram as the algebraic sum of two monophasic curves and the validity of Wilson's concept of the significance of the area, AQRS plus AT. An electronic integrator was employed to measure the areas of bipolar leads recorded from a strip of turtle ventricle which could be stimulated at either end. The close correspondence of the experimental findings with the predictions derived from the representation of the bipolar curve as the algebraic sum of two theoretical monophasic curves supports the validity of the concept tested.
Effect of Catheter Sampling on the Shape of Indicator-Dilution Curves
Authors: SHEPPARD C. W. , JONES MARSHALL P. , COUCH BILLY LANIER
Published: June 2012

The dispersion of a very short bolus of dye carried through a long cylindrical tube by a Newtonian fluid has been investigated theoretically and experimentally for two situations. In the first case a short bolus of uniform length and concentration is considered, representing a uniform amount of dye entering the tube per unit cross-sectional area independent of velocity of flow at a particular radius from the tube axis. In the second case concentration is uniform so that layers of fluid with greater velocity will carry in more dye than slower layers. Since velocities at the tube wall approach zero whereas velocities of axial dye are maximal, the axial fluid will contain greater amounts of dye per unit area. The implication of these principles to the dispersion of dye taken from deeply situated sites in the mammalian circulation through catheters of appreciable volumue is discussed.
Hemodynamic Changes in Hypophysectomized Rats
Authors: BEZNÁK MARGARET
Published: June 2012

The following changes were observed in hypophysectomized rats, 14 days after the operation: greatly reduced cardiac output, bradycardia, slight increase in total peripheral resistance, less work done by the left ventricle, low blood pressure, reduced respiratory rate and oxygen uptake, no change in blood volume and erythrocyte count. During an increased input or resistance load, the output and work of the heart rose greatly both in normal and in hypophysectomized rats. The maximum work which the heart did under these conditions, especially if the size of the heart was taken into consideration, was not significantly less in hypophysectomized than in normal rats. It is concluded that the low cardiac output after hypophysectomy is not primarily of cardiac origin.
Heart and Lungs as a Common Chamber during Extracorporeal Support of the Fibrillating Canine Heart
Authors: BELL JOHN W. , BERETTA FRANCESCO F. , GARRETT WAYNE E.
Published: June 2012

Ventricular fibrillation was induced by electric shock in both closed- and open-chest animals. Total body perfusion was provided by extracorporeal circulation with a bubble oxygenator. The failure of left heart pressure to increase during prolonged observations indicates the probable competency of the aortic valve and retrograde flow of bronchial arterial blood to the right heart. Evidence for left-to-right flow is shown by reciprocal pressures in parallel chambers, by recovery of isotope in the pulmonary artery following left heart and aortic injection and by a cardiopneumonogram. The existence of a common mean pressure in the left heart, lungs and right heart during ventricular fibrillation confirms the hypothesis that the central circulation is in essence a, system of tubes permitting the passive transfer of blood with the prevailing gradient.
Developmental changes in the beta-adrenergic modulation of calcium currents in rabbit ventricular cells.
Authors: Osaka T , Joyner R W
Published: June 2012

We studied the developmental changes in the beta-adrenergic modulation of L-type calcium current (ICa) in enzymatically isolated adult (AD) and newborn (NB, 1-4-day-old) rabbit ventricular cells using the whole-cell patch-clamp method. ICa was measured as the peak inward current at a test potential of +15 mV by applying a 180-450-msec pulse from a holding potential of -40 mV with Cs(+)-rich pipettes and a K(+)-free bath solution at room temperature. In control, ICa density (obtained by normalizing ICa to the cell capacitance) was significantly higher in AD cells (5.5 +/- 0.2 [mean +/- SEM] pA/pF, n = 65) than in NB cells (2.6 +/- 0.1 pA/pF, n = 60). Isoproterenol (ISO, 1 nM-30 microM) increased ICa in a dose-dependent manner for both groups. The maximal effect (Emax) of ISO, expressed as percent increase in ICa over control levels, and the concentration for one half of the maximal effect (EC50) were 203% and 51 nM, respectively, for AD cells and 111% and 81 nM, respectively, for NB cells. The effect of ISO (1 microM) on ICa was decreased as the test potential was increased from -10 to +40 mV. However, the ratio of the percent increase in ICa for AD versus NB cells was almost constant (2.09-2.45) at each test potential. Dose-response curves of forskolin (FOR, 0.3-50 microM) gave Emax and EC50 of 268% and 0.74 microM, respectively, for AD cells and 380% and 1.15 microM, respectively, for NB cells. After stimulating ICa by 10 microM ISO, the addition of 10 microM FOR produced a further increase in ICa of only 12 +/- 2% in AD cells (n = 4) but a further increase of 140 +/- 41% in NB cells (n = 6). FOR (10 microM) did not produce any increase in ICa for AD and NB cells after stimulating ICa by intracellular application of 200 microM cAMP. ICa density stimulated by 10 microM ISO (17.8 +/- 1.1 pA/pF, n = 7), 10 microM FOR (21.0 +/- 1.3 pA/pF, n = 8), or 200 microM cAMP (18.0 +/- 1.3 pA/pF, n = 5) was equivalent in AD cells, whereas ICa density stimulated by 10 microM ISO (5.8 +/- 0.6 pA/pF, n = 9) was significantly lower than that stimulated by either 10 microM FOR (13.8 +/- 1.5 pA/pF, n = 7) or 200 microM cAMP (13.4 +/- 0.7 pA/pF, n = 7) in NB cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Enhancement of rabbit cardiac sodium channels by beta-adrenergic stimulation.
Authors: Matsuda J J , Lee H , Shibata E F
Published: June 2012

Voltage-dependent sodium channels from a variety of tissues are known to be phosphorylated by the cAMP-dependent protein kinase, protein kinase A. However, the functional significance of sodium channel phosphorylation is not clearly understood. Using whole-cell voltage-clamp techniques, we show that sodium currents (INas) in rabbit cardiac myocytes are enhanced by isoproterenol (ISO). This enhancement of INa by ISO 1) is holding potential dependent, 2) can be mimicked by forskolin and dibutyryl cAMP, and 3) is accompanied by an increase in the rate of Na+ channel inactivation. In single-channel, inside-out patch experiments, the catalytic subunit of protein kinase A also enhances INa and increases the rate of inactivation, suggesting that cardiac Na+ channel phosphorylation may be physiologically important. Addition of the protein kinase A inhibitor to the pipette solution in whole-cell experiments blocks the stimulatory effect of forskolin without blocking the effect of ISO, suggesting that ISO also enhances INa through a cAMP-independent pathway. To determine if ISO may stimulate INa through a direct G protein pathway, single channels were recorded in the presence of the Gs-activating GTP analogue, GTP gamma S, and the stimulatory G protein subunit, Gs alpha. Both of these agents enhanced INa without affecting the rate of Na+ channel inactivation. These results suggest that ISO enhances rabbit cardiac INa through a dual (direct and indirect) G protein regulatory pathway.
ADP plays an important role in mediating platelet aggregation and cyclic flow variations in vivo in stenosed and endothelium-injured canine coronary arteries.
Authors: Yao S K , Ober J C , McNatt J , Benedict C R , Rosolowsky M , Anderson H V , Cui K , Maffrand J P , Campbell W B , Buja L M
Published: June 2012

The goal of this study was to test the hypotheses that endogenous ADP plays an important role in vivo in mediating platelet aggregation and cyclic coronary artery blood flow variations (CFVs) in stenosed and endothelium-injured coronary arteries in an experimental canine model. Anesthetized animals were studied and coronary blood flow velocities monitored by a pulsed Doppler flow probe positioned around the left anterior descending coronary artery. CFVs were established by an external constrictor positioned at sites with injured endothelium. Apyrase, an ADP-removing enzyme, was infused into the left anterior descending coronary artery (0.3-1.8 units/min) 30 minutes or 2 hours after the establishment of CFVs. Complete abolition of CFVs was achieved in 81% (13/16) of dogs with 30-minute CFVs and in 83% (five of six) of dogs with 2-hour CFVs. In other dogs, a potent inhibitor of ADP-induced platelet aggregation, clopidogrel, was administered as a 10 mg/kg i.v. bolus and a 2.5 mg/kg/hr infusion 30 minutes and 3 hours after the establishment of CFVs. This treatment resulted in complete abolition of CFVs in 14 dogs (100%) with either 30-minute or 3-hour CFVs. Epinephrine was infused into some dogs after CFVs had ceased as a result of either apyrase or clopidogrel administration and into some dogs in whom SQ29548, a thromboxane A2 receptor antagonist, had been given when apyrase failed to abolish CFVs. Epinephrine restored CFVs in all dogs treated with apyrase alone, 67% (four of six) of dogs treated with the combination of apyrase and SQ29548, and 29% (two of seven) of dogs treated with clopidogrel. The plasma epinephrine levels required for CFV restoration were 20 times higher than baseline values in dogs receiving apyrase alone, 100 times higher when a combination of apyrase and SQ29548 had been given, and more than 5,000 times higher in dogs receiving clopidogrel. In vitro studies showed that apyrase only inhibited ADP-induced platelet aggregation, whereas clopidogrel not only inhibited ADP-induced platelet aggregation, but also reduced platelet aggregation induced by the thromboxane mimetic U46619 and serotonin. These data suggest that 1) ADP is an important mediator of platelet aggregation and CFVs in vivo and 2) combined inhibition of thromboxane A2 and ADP's effects provides marked protection against CFVs in experimentally stenosed and endothelium-injured canine coronary arteries. These data and our previous observations are consistent with the possibility that specific antagonists of thromboxane A2, serotonin, and ADP, alone and together, may provide substantial protection against platelet aggregation leading to CFVs at sites of endothelial injury and coronary artery stenosis.
Atrial and brain natriuretic peptides inhibit the endothelin-1 secretory response to angiotensin II in porcine aorta.
Authors: Kohno M , Yokokawa K , Horio T , Yasunari K , Murakawa K , Takeda T
Published: June 2012

We have recently shown that the porcine aorta releases immunoreactive endothelin-1 in a time-dependent way. Here, we examined the inhibition by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) of endothelin-1 secretion after stimulation with angiotensin II (Ang II) by using porcine aorta. Ang II dose-dependently stimulated immunoreactive endothelin-1 secretion. Porcine ANP-(1-28) and porcine BNP-26 both inhibited such secretion in a dose-dependent way. The addition of a cyclic guanosine 5'-monophosphate (cGMP) analogue, 8-bromo-cGMP, reduced the immunoreactive endothelin-1 secretion after stimulation with Ang II. In cultured porcine endothelial cells the inhibition by porcine ANP-(1-28) and porcine BNP-26 of immunoreactive endothelin-1 secretion after stimulation with Ang II was paralleled by an increase in the cellular cGMP level. Rat ANP-(5-25) was weaker than porcine ANP-(1-28) in inhibiting immunoreactive endothelin-1 secretion and increasing cGMP in cultured cells. There was negative correlation between the percent decrease in immunoreactive endothelin-1 and the percent increase in cGMP. Neither porcine ANP-(1-28) nor BNP-26 affected the number or sensitivity of Ang II binding sites in cultured porcine endothelial cells. These results suggest that ANP and BNP inhibit endothelin-1 secretion after stimulation with Ang II, probably through a cGMP-dependent process.
Alterations in myofibrillar function and protein profiles after complete global ischemia in rat hearts.
Authors: Westfall M V , Solaro R J
Published: June 2012

We studied changes in myofibrillar function and protein profiles after complete global ischemia with anoxia in rat hearts. Hearts were exposed to global ischemia and anoxia (CGI) for 30 or 60 minutes at 37 degrees C, and myofibrils were prepared for measurement of Ca(2+)-dependent Mg(2+)-ATPase activity at pH 7.0 and 6.5. Hearts incubated in cold saline (1 +/- 1 degrees C) and nonincubated hearts served as controls. Maximum ATPase activity was unchanged at pH 7.0 and pH 6.5 in myofibrils from hearts treated with 30 or 60 minutes of CGI. At pH 7.0, the Hill coefficient, which is an index of cooperative interactions among thin-filament proteins, was unchanged after 30 minutes of CGI but was significantly increased after 60 minutes of CGI. A similar trend for increased cooperativity was observed when myofibrillar ATPase activity was measured at pH 6.5 in myofibrils from rat hearts made ischemic for 30 or 60 minutes. Both 30 and 60 minutes of CGI resulted in increased pCa50 values (half-maximally activating free [Ca2+]) at pH 7.0 and pH 6.5. Densitometric analysis of myofibrillar proteins separated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that troponin I and troponin T were degraded during 60 minutes of CGI. Two new protein bands appearing in ischemia-treated myofibrils were identified as partially degraded troponin I and troponin T with Western blots. The troponin I fragment could be phosphorylated by cAMP-dependent protein kinase. In addition, we observed phosphorylation of a protein band that corresponded to myosin light chain-2 in myofibrils from CGI-treated hearts. These results suggest that degradation of thin-filament proteins may contribute to the changes in cooperativity of Ca2+ regulation of ATPase activity observed in the myofibrils from rat hearts exposed to CGI.