bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of human platelet aggregation and cytoplasmic calcium response by calcium antagonists: studies with aequorin and quin2.
Authors: Ware J A , Johnson P C , Smith M , Salzman E W
Published: June 2012

Calcium antagonists inhibit platelet aggregation, but whether this action is due to inhibition of the effect of agonists on cytoplasmic ionized calcium concentration is unknown. We studied this problem by loading gel-filtered platelets with either quin2 or aequorin and stimulating them with epinephrine, arachidonate, thrombin, the calcium ionophore A23187, 1-oleoyl-2-acetyl glycerol, or adenosine diphosphate in media with or without extracellular calcium. In response to all of these agonists, aequorin indicated an increase in cytoplasmic calcium that accompanied or preceded platelet aggregation. In calcium-containing media, verapamil, nifedipine, and diltiazem inhibited these effects in a concentration-dependent fashion, except for those produced by thrombin and A23187. Removal of extracellular calcium with EGTA reduced the calcium response to arachidonate, adenosine diphosphate, and 1-oleoyl-2-acetyl glycerol, and the calcium response and aggregation were further inhibited by the calcium antagonists. In general, strong inhibition of the aequorin cytoplasmic calcium signal by approximately 100 microM concentrations of nifedipine, verapamil, and diltiazem was correlated with inhibition of platelet aggregation, but high concentrations of the inhibitors were required. Since inhibition by the calcium antagonists of the cytoplasmic calcium response and aggregation exceeded the effect of simple removal of extracellular calcium, these drugs may affect internal redistribution of calcium in human platelets.
The effect of atrial natriuretic factor on blood pressure, heart rate, and renal functions in conscious, spontaneously hypertensive rats.
Authors: Gellai M , DeWolf R E , Kinter L B , Beeuwkes R
Published: June 2012

Atrial natriuretic factors, polypeptides released by atrial myocytes, may play a role in the control of blood pressure and the regulation of renal salt and water excretion. Our studies were designed to assess the role of a synthetic peptide, atriopeptin II, on blood pressure and heart rate, renal hemodynamics, and salt and water excretion in conscious, spontaneously hypertensive rats and in normotensive Wistar-Kyoto rats. Changes in mean arterial pressure and heart rate were recorded following intravenous bolus injections (0.1, 1.0, 10, 100 micrograms/kg) of atriopeptin II in 5 spontaneously hypertensive and 5 Wistar-Kyoto rats. In a second group of rats the peptide was infused for 90 minutes in two different doses: low dose, 1 microgram/kg + 2 micrograms/kg/hr; and high dose, 10 micrograms/kg + 20 micrograms/kg/hr. Bolus injections of atriopeptin II resulted in dose-dependent decreases in mean arterial pressure in the hypertensive, but not in the normotensive, rats; heart rates remained unchanged. Blood pressure decreased gradually during the sustained infusion of both doses of atriopeptin II, with the spontaneously hypertensive strain showing increased sensitivity compared to the Wistar-Kyoto strain. Heart rate decreased in both strains during infusion of the high dose; the decrease was significant only in the hypertensive rats. The low dose of atriopeptin II increased the clearance of free water in both strains of rats; sodium excretion was increased only in the hypertensive rats. The high-dose atriopeptin II was associated with transient natriuresis, unaltered glomerular filtration rate, and decreased effective renal blood flow in both strains.(ABSTRACT TRUNCATED AT 250 WORDS)
Biphasic contractions induced by milrinone at low temperature in ferret ventricular muscle: role of the sarcoplasmic reticulum and transmembrane calcium influx.
Authors: Malecot C O , Bers D M , Katzung B G
Published: June 2012

The effects of milrinone were studied in ferret papillary muscle stimulated at various rates and temperatures from 23 degrees to 36 degrees C. In voltage-clamp experiments, 50 micrograms/ml (0.237 mM) milrinone induced a 2.1-fold increase in calcium current at 28 degrees or 36 degrees C. At 50 micrograms/ml, milrinone transiently increased contractility in all muscles at 28 degrees C, but its steady-state effect was either increased (+50%) or decreased (-24.7%) steady-state twitch amplitude. A negative inotropic effect always occurred below 27 degrees C. Milrinone decreased the total twitch duration and split the twitch into two components (P1 and P2) in the absence of any evidence of aberrant conduction. Increasing milrinone concentration from 50 to 300 micrograms/ml decreased P1 and increased P2. Ryanodine (100 mM) or caffeine (10 mM) suppressed P1. Contractions elicited after 30 seconds of rest were also biphasic in the presence of milrinone, but not in its absence. P2 of post-rest contraction was increased by caffeine or calcium (10 mM) and decreased by cobalt (2 mM) when drugs were applied at the beginning of the rest. Ryanodine and caffeine also suppressed P1 of post-rest contraction. The evidence suggests that P1 may be caused by Ca release from the sarcoplasmic reticulum and P2 by increased Ca influx during the action potential via the calcium channel. It is also suggested that P2 may be present under control conditions, but to a lesser extent, and masked by a large P1.
Stimulation of DNA synthesis in rat A10 vascular smooth muscle cells by threonine-59 insulin-like growth factor I.
Authors: Cascieri M A , Chicchi G G , Hayes N S , Slater E E
Published: June 2012

The clonal smooth muscle cell line A10, derived from fetal rat aorta, binds 125I-insulin-like growth factor I at a Type 1 insulin-like growth factor receptor. Threonine-59 insulin-like growth factor I, multiplication stimulating activity, and insulin inhibit the binding with IC50 = 10 nM, 84 nM, and 500 nM, respectively. Insulin in high concentrations (greater than 5 microM) completely inhibits 125I-insulin-like growth factor I binding to A10 cells. Threonine-59 insulin-like growth factor I and insulin stimulate [3H]thymidine incorporation into DNA in A10 cells that had been growth arrested by incubation in serum-free media (DMEM/0.1% BSA) for 24-36 hours. The stimulation produced by the peptides is 50-60% of the stimulation produced by 10% fetal calf serum. Low levels of serum (0.1 and 0.5%) also stimulate DNA synthesis, and the effects of Threonine-59 insulin-like growth factor I and low serum are additive. The ED50 for the effects of Threonine-59 insulin-like growth factor I, multiplication stimulating activity, and insulin are 6.8 +/- 0.3 nM, 36 +/- 2.5 nM, and 360 +/- 242 nM, respectively. Incubation of A10 cells for 24 hours with Threonine-59 insulin-like growth factor I or serum increases the protein content per culture dish by 85 +/- 21 and 183 +/- 26%, respectively (mean +/- SEM). Thus, both protein levels and DNA synthesis are increased by incubation with peptides. However, Threonine-59 insulin-like growth factor I does not increase the number of cells in serum starved cultures, although 10% fetal calf serum does.(ABSTRACT TRUNCATED AT 250 WORDS)
Micropuncture measurement of microvascular pressures in isolated lamb lungs during hypoxia.
Authors: Raj J U , Chen P
Published: June 2012

To study the effect of alveolar hypoxia on the pulmonary circulation of the newborn, we determined the longitudinal distribution of vascular pressures and the distribution of blood flow in isolated blood perfused lungs of newborn lambs during normoxia and hypoxia. We also examined the effect of hypoxia on the slope and intercept of the vascular pressure-flow (P/Q) relation. In 14 lungs, we used the micropipette servonulling technique to measure pressures in 20-80 micron subpleural arterioles and venules during normoxia and hypoxia at constant blood flow. In 5 other lungs, we used radiolabelled microspheres to determine the effect of hypoxia on regional distribution of blood flow. Under baseline normoxic conditions, segmental pressure drops in arteries, microvessels, and veins were approximately equal. During hypoxia pulmonary artery pressure always increased, resulting in a 60% increase in total vascular resistance. All segmental pressure drops increased with hypoxia. Arterial and venous pressure drops increased by 80 and 70% respectively, contributing almost equally to the increase in total pulmonary vascular resistance. Regional distribution of blood flow was uniform during normoxia and was unchanged during hypoxia. Hypoxia increased both the slope and intercept of the P/Q relation significantly, with an increase in fluid filtration rate. We conclude that in the newborn lamb alveolar hypoxia leads to pulmonary arterial and venous constriction, resulting in increased microvascular pressure and fluid filtration.
Effect of hypercholesterolemia on vascular reactivity in the rabbit. II. Influence of treatment with dipyridamole on endothelium-dependent and endothelium-independent responses in isolated aortas of control and hypercholesterolemic rabbits.
Authors: Verbeuren T J , Coene M C , Jordaens F H , Van Hove C E , Zonnekeyn L L , Herman A G
Published: June 2012

The effects of cholesterol-feeding in the presence of dipyridamole (0.60 g daily) on contractile responses and on endothelium-dependent and endothelium-independent relaxations in isolated rabbit aortas are described. The investigations were performed simultaneously with those described in Part I (Circ Res 1986; 58:552-564), where the effects of cholesterol feeding on vascular reactivity in rabbit arteries (n = 8 in each group) selected at random from the same group of animals was studied. In the hypercholesterolemic rabbits treated with dipyridamole for 8 or 16 weeks, both the increases in plasma cholesterol and the formation of fatty streaks were significantly less pronounced than in the hypercholesterolemic rabbits not receiving the drug. Segments of the isolated arteries were mounted in organ chambers for isometric tension recording. The contractions caused by acetylcholine, prostaglandin F2 alpha, norepinephrine, clonidine, and serotonin and the endothelium-independent relaxations to nitroglycerin were not significantly altered by the hypercholesterolemia in rabbits treated with dipyridamole, even after 16 weeks of treatment. Thus, the decreased responses to norepinephrine, clonidine, and nitroglycerin and the augmented responses to serotonin noted in aortas of hypercholesterolemic rabbits in Part I were absent in the dipyridamole-treated hypercholesterolemic animals. The endothelium-dependent relaxations to ATP and acetylcholine were not affected after 8 weeks of hypercholesterolemia in presence of dipyridamole, while after 16 weeks the relaxations to ATP and acetylcholine were attenuated only in the more severely affected arteries. The effects of hypercholesterolemia + dipyridamole on endothelium-dependent relaxations were significantly less pronounced than those induced by hypercholesterolemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of large coronary arteries.
Authors: Young M A , Vatner S F
Published: June 2012

The majority of studies on the control of coronary artery vasoactivity have examined changes in coronary blood flow and coronary vascular resistance, indices that primarily reflect regulation of small arterioles and precapillary vessels. With the emergence of coronary artery vasospasm as a significant cause of angina pectoris, myocardial infarction, and sudden death, the control of large coronary artery caliber has assumed more significance. It is clear that resistance coronary vessels and large coronary arteries differ in response to both pharmacologic and physiologic stimuli. Vasodilation of large coronary arteries may occur by direct action of agents on the arterial smooth muscle or by the indirect action of receptor occupation, changes in blood flow, or liberation of endothelial factors. These indirect factors appear to contribute also to responses to agents that constrict coronary smooth muscle directly or through the autonomic nervous system. Furthermore, the mechanisms responsible for control of large coronary vessels in the normal circulation are likely to be profoundly different from those in the presence of diseased vessels. For example, several factors associated with coronary artery disease--elevated plasma cholesterol levels, endothelial disruption, atherosclerosis, vascular stenosis, and aggregated platelets--all have important actions on the control of large coronary arteries.
Effects of lung inflation on blood flow during cardiopulmonary resuscitation in the canine isolated heart-lung preparation.
Authors: Hausknecht M J , Wise R A , Brower R G , Hassapoyannes C , Weisfeldt M L , Suzuki J , Permutt S
Published: June 2012

Using an isolated, fibrillated canine heart-lung preparation, we studied the effects of simultaneous lung inflation and chest compression on blood flow in a model of cardiopulmonary resuscitation. The heart and lungs were placed in an artificial thorax with the great vessels and trachea exteriorized and attached to an artificial perfusion circuit and respirator, respectively. The blood volume of the system was adjusted to obtain various levels of static equilibrium pressure. Blood flow was obtained by cyclically raising and lowering the pressure in the artificial thorax, simulating the changes in pleural pressure that occur during cardiopulmonary resuscitation. Lung inflation during the compression phase caused an increase in cardiopulmonary resuscitation blood flow when the change in pleural pressure was small and when static equilibrium pressure was high. In contrast, lung inflation caused a decrease in blood flow when changes in pleural pressure were high and when blood volume was low. These results suggest that the driving pressure for blood flow during chest compression may be increased by lung inflation when the pulmonary blood vessels are filled with blood. However, blood may become trapped in the right heart and unavailable for transfer to the periphery during chest compression if lung inflation causes the alveolar blood vessels to collapse.
Regulation by calcium of arachidonic acid metabolism in the isolated perfused rabbit heart.
Authors: Weis M T , Malik K U
Published: June 2012

Activation of beta-adrenergic receptors with isoproterenol fails to stimulate prostaglandin synthesis in the isolated rabbit heart perfused with Ca2+-free Krebs-Henseleit buffer. This lack of response could be due to reduced isoproterenol-stimulated liberation of arachidonic acid, reduced cyclooxygenase activity during Ca2+-free perfusion, or both. To test these hypotheses, we have examined the effect of isoproterenol and exogenous arachidonic acid on prostaglandin output in hearts perfused with Ca2+-containing and nominally Ca2+-free Krebs-Henseleit buffer. In hearts prelabelled with [3H]arachidonic acid and perfused with nominally Ca2+-free buffer, the release of radioactivity following isoproterenol was about 90% less than when Ca2+ was included in the perfusion buffer. When exogenous arachidonic acid was administered to hearts perfused with Ca2+-depleted buffer, the output of both 6-keto-prostaglandin F1 alpha and prostaglandin E2 was about threefold greater than when Ca2+ was present in the perfusion medium. In the absence of Ca2+, the dose response curve for arachidonic acid-induced 6-keto-prostaglandin F1 alpha synthesis underwent a parallel shift to the left, with no change in maximal synthesis levels, and a tenfold reduction in the ED50 of arachidonic acid. The cyclooxygenase activities of cell-free homogenates prepared from hearts perfused with and without Ca2+ were not different from each other and were both insensitive to added Ca2+. Reduction of the Na+ concentration of the perfusion medium to 35 mM resulted in increases in arachidonic acid-induced 6-keto-prostaglandin F1 alpha less than those obtained during Ca2+-free perfusion, but greater than that observed during perfusion with normal Na+ (139 mM) and Ca2+ (2.5 mM). Arachidonic acid induced 6-keto-prostaglandin F1 alpha output was inversely correlated with tissue Ca2+ but not Na+ content. These data suggest that in the absence of perfusate Ca2+, the availability of exogenous arachidonic acid to cyclooxygenase is increased, possibly by reduced incorporation into tissue phospholipids.
Physical Effects of Increased Venous and Extrarenal Pressure on Renal Vascular Resistance
Authors: WAUGH WILLIAM H. , HAMILTON WILLIAM F.
Published: June 2012

The oil perfused kidney preparation was used to determine the passive effects of increased venous and extrarenal pressure on renal vascular resistance. The dimensional tube factor of renal resistance varied inversely with the arteriovenous pressure gradient because this pressure difference also determined the pressure difference across the walls of the intrarenal vessels.
Simultaneous Comparison of Antegrade and Collateral Coronary Blood Flows
Authors: DE VERA LAURO B. , GOLD HERBERT , CORDAY ELIOT
Published: June 2012

Comparison of the antegrade and retrograde (collateal) coronary free flows showed that the retrograde flow was less than 10 per cent of the antegrade flow in 48 per cent of animals and above 20 per cent in 11 per cent of animals.
The Frequency-Dependent Nature of Blood Pressure Regulation by the Carotid Sinus Studied with an Electric Analog
Authors: WARNER HOMER R.
Published: June 2012

Amplification of carotid sinus activity of a dog is brought about through the use of an electric analog of the carotid sinus applied in parallel with this element of the dog's own pressure regulating system. Sinusoidal excursions in arterial pressure in response to corresponding variations, between fixed limits, in rate of stimulus of one vagus nerve were larger with carotid sinus amplification than without it. Evidence presented supports the concept that because of the delay in the response of arteriolar smooth muscle, effective buffering of sudden variations in arterial pressure cannot be accomplished by variations in resistance, but can be through variations in flow.
Estimation of Venous Blood Volume in the Dog by the Indicator-Dilution Method
Authors: MILNOR W. R. , BERTRAND C. A.
Published: June 2012

The indicator-dilution method of determining cardiac output and mean transit times can be employed to estimate indirectly the volume of blood in the larger veins in vivo although it is difficult to define precisely the peripheral anatomic boundaries of the volume so measured. In 12 anesthetized dogs the "venous" blood volume obtained by multiplying cardiac output and mean transit time from femoral vein to right atrium averaged 16.6 ml./Kg., or 18 per cent of total blood volume. Rapid intravenous infusion of dextran solution caused no significant change in the blood volume of the large veins, heart or lungs.
Hemodynamics of Intestinal Circulation
Authors: SELKURT EWALD E. , SCIBETTA MARIO P. , CULL THEODORE E.
Published: June 2012

The pressure-flow relationship was studied in isolated denervated intestinal loops of the dog in a range of pressure varying from 0 to 240 mm. Hg. The relationship was curvilinear, convex to the pressure axis. Flow started at a minimal pressure of 16 mm. Hg, then increased more rapidly than pressure up to 240 mm. Hg. Critical closure, passive expansion of vessels with rising intraluminal pressure, and anomalous viscosity of blood appeared to be the important factors influencing vascular resistance and flow in the present studies.
Blood and Plasma Specific Gravity Changes During Acute Alterations in Hemodynamics in Splenectomized Dogs
Authors: REMINGTON J. W. , BAKER C. H.
Published: June 2012

A variety of procedures were used to change hemodynamics acutely and thereby to produce changes in blood volume. Changes in plasma specific gravity showed no relation to those in aortic pressure or total peripheral resistance, but were related to central venous pressure. The simultaneous cell fraction tended to vary reciprocally with the plasma specific gravity, indicating a bulk transfer of either red cells or of plasma between the large blood vessels and peripheral beds.
Failure of Parenterally Administered Pyridoxine to Influence Serum Cholesterol Levels and Development of Atherosclerosis in Cholesterol-Fed Rabbits
Authors: MARTENS FRED W. , HOSKINS DONALD W.
Published: June 2012

Pyridoxine administered parenterally was found to have no effect on serum cholesterol levels of rabbits fed a normal diet, nor did it inhibit the development of hypercholesterolemia and atherosclerosis in rabbits fed a cholesterol-rich diet.
Cholesterol Metabolism in Gonadectomized Rats
Authors: COLEMAN RICHARD D. , CHEN YU MIN , ALFIN-SLATER ROSLYN B.
Published: June 2012

In studies in which tissue concentrations of cholesterol and total lipids were determined in male and female rats fed a control diet containing fat, the effects of gonadectomy were much smaller than in animals fed a fat-free diet in which gonadectomy tended to reverse the sex differences observed in these lipid values. Other phases of lipid metabolism were shown to be sex-linked as well. Gonadectomy resulted in decreased synthesis of cholesterol in rat liver slices and changes in the fatty acid composition of cholesterol esters in the liver.
Decrease of Serum Cholesterol in Rabbits Following Chloroform Inhalation and as Diurnal Variation
Authors: FEDOROFF M. ELAINE , ALTSCHUL R.
Published: June 2012

Normal rabbits were exposed to single, subanesthetitizing doses of chloroform vapors and a regular decrease in their total serum cholesterol was found. In rabbits with abnormally high serum cholesterol levels, however, no consistent changes were observed. In control experiments it was found that in the normal rabbit there is a diurnal variation in serum cholesterol, with lowest values around 4 p.m. No consistent changes were found in the serum cholesterol of rabbits after being submerged for brief periods in ice water.
Studies of the Effect of Antiarrhythmic Drugs on Carbohydrate Metabolism of Rat Heart Muscle in Vitro
Authors: HESS MARILYN E. , HAUGAARD NIELS
Published: June 2012

The effect of antiarrhythmic drugs on the oxidation of glucose by heart tissue was studied. Quinine and quinidine inhibited oxygen consumption and glucose utilization by rat heart slices and homogenates, while chloroquine and procaine amide had little effect.
Influence of Blood Temperature on the Pulmonary Circulation
Authors: GALLETTI PIERRE M. , SALISBURY PETER F. , RIEBEN ANDRE
Published: June 2012

Innervated, nourished and ventilated dog lungs were perfused in situ with a technic which afforded adequate control of blood flow, pressures, pH and temperature. Variations of the pulmonary (hut not of the systemic) blood temperature was followed by pronounced changes of the pulmonary vascular resistance, believed to be attributable to pulmonary vasomotion.
Measurement and Radioautographic Localization of Albumin in Rat Tissues After Intravenous Administration
Authors: EVERETT NEWTON B. , SIMMONS BARBARA
Published: June 2012

Radioautography and conventional counter methods have been used to determine the relative amount and localization of I
131
albumin in a number of tissues at 3, 30, and 60 min. after intravenous injection. Certain tissues showed essentially no change in albumin content with time, others contained extravascular albumin which increased with time, and the liver and adrenal evidenced a decreasing level of albumin with time. The transcapillary passage of albumin and its accumulation in extravascular compartments are correlated with tissue structure.
Translocation of Blood from the Isolated Dog's Hindlimb During Levarterenol Infusion and Sciatic Nerve Stimulation
Authors: SHADLE OSCAR W. , ZUKOF MARTIN , DIANA JOHN
Published: June 2012

Changes in weight, arterial and peripheral venous pressures, and venous outflow were measured during levarterenol infusion and sciatic nerve stimulation in an isolated hindlimb with constant arterial inflow. Our results indicate that the weight loss which occurs during these procedures is caused by peripheral venous constriction, and that the loss of volume from the hindlimb is almost entirely from the intravascular compartment.
Renal, Transcapillary, Net Exchange in the Dog
Authors: FREIS EDWARD D. , SCHNAPER HAROLD W. , ROSE JOHN C. , LILIENPIELD LAWRENCE S.
Published: June 2012

The transcapillary net exchanges of inulin, para-aminohippurate, thiocyanate and heavy water were determined in the renal circulation. It was found that the tracer substances larger than heavy water diffused more freely through renal than through previously studied peripheral or pulmonary capillaries. The results are consistent with the concept of a larger pore size in renal capillaries.
Relationship of Appearance of Abnormal Plasma Hemin Pigment to Development of Irreversible Hemorrhagic Shock in Dogs
Authors: LILLEHEI RICHARD C.
Published: June 2012

Irreversible hemorrhagic shock in dogs was associated with a progressive rise in plasma hemoglobin levels and the appearance of an abnormal hemin pigment in the plasma. Both findings were related to mucosal necrosis of the bowel occurring as a result of prolonged hemorrhagic shock. In dogs perfused through the superior mesenteric artery during hemorrhagic shock, the bowel remained normal, irreversibility was prevented and the abnormal plasma findings did not occur.
Effect of Nicotinic Acid on the Incorporation of Radiocarbon into Cholesterol
Authors: MERRILL JOSEPH M.
Published: June 2012

Nicotinic acid when fed to rats as 0.8 per cent of their diet caused an 83 per cent increase in radioactivity of liver cholesterol-digitonin precipitate. In vitro studies using rat liver slices indicated that nicotinic acid increased the incorporation of radiocarbon into cholesterol by 46 per cent.
Arrhythmic and Antiarrhythmic Effects of Sodium, Potassium, and Calcium Salts and of Glucose Injected into Coronary Arteries of Infarcted and Normal Hearts
Authors: HARRIS A. SIDNEY , TOTH LOUIS A. , HOEY TAN ENG , Burford Dunca D. , Liptak Richard A. , Anwar Djamadina
Published: June 2012

Substances that have not exhibited properties as excitants of ectopic activity by intracoronary injection into normal hearts often produce rapid ectopic activity and sometimes ventricular fibrillation upon slow injection through the vascular bed of an infarcted area, particularly upon the first one or two injections. Sodium lactate has reduced and stopped ectopic activity for brief periods. Excesses of both potassium and calcium have increased ectopic activity in infarction and produced it in normal hearts. No antagonism between these two ions, with respect to ectopic activity, has been demonstrated.
Influence of Levarterenol on Portal Venous Flow in Acute Hemorrhage
Authors: LEVY MATTHEW N. , Arthur F. Flatly , Zieske Harrison
Published: June 2012

In anesthetized dogs, the effects of hemorrhage alone upon the mesenteric circulation have been compared with those of hemorrhage plus l-norepinephrine. With norepinephrine, the portal venous flow is slightly less than in the case of untreated hemorrhage. In view of the significantly higher blood pressure during the norepinephrine infusions, however, the mesenteric resistance is considerably greater during infusions of this agent than in untreated hemorrhage.
Effect of Acute Elevation of Portal Venous Pressure on Mesenteric Blood Volume, Interstitial Fluid Volume and Hemodynamics
Authors: SELKURT EWALD E. , JOHNSON PAUL C.
Published: June 2012

Measurement of blood flow through the portal vein of the dog revealed a reduction of flow and an increase in vascular resistance of the mesenteric bed in proportion to the elevation of portal venous pressure. To obtain further information on this mechanism, studies were performed on segments of terminal ileum with continuous measurement of both weight and flow. These studies demonstrated that the increase of vascular resistance was not dependent upon extrinsic or adrenergic innervation, and did not appear to be secondary to interstitial fluid formation. It is suggested that the response in this bed is due to a local reflex to a myogenic reaction of the resistance vessels to increased transmural pressure.
Functional Capillary Beds in the Beating, KCl-Arrested and KCl-Arrested-Perfused Myocardium of the Dog
Authors: REYNOLDS S. R. M. , KIRSCH M. , BING R. J.
Published: June 2012

Dog hearts were taken without loss of blood under 3 different conditions: (1) normally beating hearts, (2) hearts that were arrested by potassium chloride for varying lengths of time and (3) potassium chloride-arrested hearts that were reperfused with blood after varying lengths of time. In normal hearts counts of open capillaries containing erythrocytes showed a uniform distribution throughout the right myocardium and a gradient decreasing from the epicardium toward the endocardium in the left myocardium. Potassium chloride-arrested hearts showed a reverse gradient in the left myocardium. In normal hearts, erythrocytes are oriented in capillaries so that their flat sides lie against the nearest myocardial cell. In the arrested hearts, one sees few or no erythrocytes with this orientation. The erythrocytes in the arrested hearts are swollen, rounded, or packed in clumps in the capillaries. Arrested hearts exhibit a weakening of the connective tissue elements of the myocardium, evident upon fixation or on perfusion of the myocardium with blood. The weakening increases as the length of myocardial arrest increases.
Effects of Autonomic Nerves and Their Mediators on the Coronary Circulation and Myocardial Contraction
Authors: DENISON ADAM B. , GREEN HAROLD D. , Dawson Earl B. , Kitchen Thomas W.
Published: June 2012

Mean and phasic coronary flows were recorded simultaneously by an electromagnetic meter, and peripheral coronary pressure was recorded distally from the temporarily occluded descending branch of the left coronary artery. From the results of these studies we conclude that: 1. The sympathetic cardiac nerves, as does levarterenol, increase myocardial contraction, (indicated by a shorter, more abrupt systole and more rapid isometric relaxation), and cause a slight degree of coronary arteriolar dilation. 2. Parasympathetic fibers exert no significant effect, although acetylcholine diminishes coronary arteriolar tone and may slightly diminish ventricular contraction. 3. That measurements of mean coronary flow and resistance are relatively satisfactory for indicating changes in coronary arteriolar tone, but are of relatively little value in evaluating myocardial contraction.
Acetyicholine and Electrolyte Metabolism in the Various Chambers of the Frog and Turtle Heart
Authors: MAZEL PAUL , HOLLAND WILLIAM C.
Published: June 2012

Evidence has accumulated suggesting acetylcholine may he involved in initiation of the heart heat. Acetylcholine and electrolyte metabolism in the various chambers of the heart have been studied. The area of highest intrinsic rhythm (sinus) contained greater amounts of acetylcholine equivalents, true cholinesterase, choline acetylase and sodium; all of these decreasing in amount in areas of lower intrinsie rhythm. It is concluded that intrinsic rhythm may he directly correlated with overall acetylcholine metabolism and sodium content and inversely related to overall energy metabolism and potassium concentration.
Effect of Purine and Pyrimidine Ribosides on an Isolated Frog Ventricle Preparation
Authors: COOK MARGARET H. , GREENE ERNEST A. , LORBER VICTOR
Published: June 2012

Various purine and pyrimidine ribosides, with the exception of adenosine, have been found to exhibit a positive inotropic effect on an isolated strip of frog ventricle. In a preparation responding maximally to one compound, the addition of a second compound led to a further increase in tension. This relationship was found to apply among the members of a given group (purine or pyrimidine) paired in various combinations, as well as in experiments pairing purine against pyrimidine riboside. Adenosine showed brief stimulation followed by depression, pure depression or no effect.
An examination of the measurement of flow heterogeneity in striated muscle.
Authors: Duling B R , Damon D H
Published: June 2012

This review leads us to a number of conclusions and suggestions for further study. First, we find wide differences in the meaning of flow heterogeneity, arising as a result of the different methods used. These differences will have to be reconciled to form a comprehensive view of the role of heterogeneity in determining vascular function. Second, in the future, the meaning of heterogeneity must be clearly defined and related to a particular microvascular component, and it is imperative that the differences in scale of heterogeneity be appreciated when comparing data from various laboratories. These heterogeneities have different implications for function, and failure to distinguish among them leads to confusion. Third, the degree to which perfusion heterogeneity is regulated in the microcirculation remains in doubt. Reports of variations in flow heterogeneity in response to physiological stimuli are for the most part based on highly questionable indirect methods. Fourth, the heterogeneity that can be demonstrated at the capillary level within striated muscle does not appear to be large relative to the capacity for the microcirculation to exchange most diffusible solutes. Thus, the inferences regarding heterogeneity, as evidenced by diffusible indicators, are likely to be the result of different preparations, damage to the preparations, or perhaps large-scale heterogeneities in the tissue. An alternate possibility would be that the heterogeneity occurs at the microvascular level but reflects some other aspect of microcirculatory function, such as length or hematocrit heterogeneities, but not flow heterogeneities. Fifth, flow heterogeneity within microvessels implies important consequences for capillary exchange and tissue oxygenation. Heterogeneities of velocity of a magnitude comparable to those observed by direct visualization of microcirculation can clearly produce reductions in oxygen supply to small tissue regions of a degree that may limit oxygen delivery, and thereby, tissue function. Sixth, flow heterogeneity may also influence capillary hematocrit and/or red cell spacing by producing cell separation at bifurcations and a resultant reduction in mean capillary tube hematocrit. There is as yet no agreement on why and how these hematocrits influence tissue oxygenation and function. Although several hypotheses are advanced to explain the distribution of blood flow and red cells within microcirculation, each lacks a critical experimental test at present.(ABSTRACT TRUNCATED AT 400 WORDS)
Pressure-induced myogenic activation of cat cerebral arteries is dependent on intact endothelium.
Authors: Harder D R
Published: June 2012

These studies were designed to determine the role of cerebral vascular endothelium in the "myogenic" depolarization and contraction observed in isolated cat middle cerebral arteries exposed to high transmural pressures. With intact endothelial cells we observed, on elevation of transmural pressure in cannulated isolated arteries, significant membrane depolarization, action potential generation, and reduction in internal diameter. After perfusion of the same vessels with collagenase and elastase for short periods of time to disrupt the endothelial layer, all previous responses to elevation of transmural pressure were no longer seen. Even though enzyme perfusion had no effect on membrane potential at "control" levels of transmural pressure, it abolished the pressure-dependent depolarization, action potential generation, and constriction. Furthermore, the contractile response to agonist stimulation was maintained after endothelial disruption via enzymes, showing that this method of endothelial disruption did not appreciably damage muscle cells. The data document a dependence of an intact endothelium in mediating the activation of isolated cat cerebral arteries in response to a changing transmural pressure. Thus, it is possible that the endothelial cell may serve as a transducer in the autoregulatory response to pressure.
Mechanism of increased amplitude and duration of the plateau with sudden shortening of diastolic intervals in rabbit ventricular cells.
Authors: Hiraoka M , Kawano S
Published: June 2012

Action potentials and membrane currents were recorded from isolated single ventricular cells from rabbit hearts using the suction pipette whole-cell clamp method. Action potentials elicited after short diastolic intervals of less than 2 seconds showed an increase and prolongation of the plateau compared to those elicited after a 10-second rest period. The recovery of the tetrodotoxin-insensitive secondary inward current revealed a transient increase at short diastolic intervals above the level of full recovery (after 10 seconds). The increased secondary inward current recovery, however, was voltage-dependent, and the period of its increase did not cover the entire diastolic intervals of the action potential overshoots, suggesting the contribution of another ionic current to the changes in potential. During depolarizing voltage steps, from + to -20 mV, a rapid activating and then inactivating outward current was elicited, which overlapped the calcium current. This outward current exhibited time- and voltage-dependent properties similar to those of the transient outward current in Purkinje and other cardiac preparations. The recovery of the transient outward current was slow, achieving only 75% of its full level at 2 seconds, whereas the same level of calcium current recovery was achieved at 200 milliseconds. The application of 4-aminopyridine suppressed most of the transient outward current, and the rest of the current was abolished by caffeine or Co2+. The 4-aminopyridine sensitive transient outward current exhibited slow recovery kinetics compared to those of the other or calcium current, and its inhibition caused elimination of the augmented plateau during electrical restitution. The application of verapamil or Co2+ for inhibition of secondary inward current also abolished the action potential overshoot. These results indicate that an increase and prolongation of the plateau at short diastolic intervals are produced by the slower recovery from inactivation in the 4-aminopyridine-sensitive transient outward current than that in the calcium current.
Influence of thyroid state on mechanical restitution of rat myocardium.
Authors: Poggesi C , Everts M , Polla B , Tanzi F , Reggiani C
Published: June 2012

The purpose of this study was to determine whether thyroid state affects the beat-to-beat regulation of contractile strength in cardiac muscle. Transmembrane action potential and isometric force were simultaneously recorded in right ventricular papillary muscles from euthyroid, hypothyroid, and hyperthyroid rats. Large thyroid state-dependent alterations in the contractile response of the muscles were not accompanied by any significant difference in the action potential. During steady-state stimulation, single test stimuli were interpolated at varying intervals. Action potential duration and peak force of the test responses were plotted against the test stimulus interval to produce electrical and mechanical restitution curves. In all muscles studied, electrical and mechanical restitution followed different time courses; over a wide range of test intervals, action potential duration and peak force of the test responses changed in opposite directions. Thyroid state profoundly affected the recovery of contractile strength, while only minor differences were found among the electrical restitution curves of the three groups of preparations. Mechanical recovery was much faster in hyperthyroid and slower in hypothyroid than in euthyroid muscles. We conclude that electrical and mechanical restitutions occur through separate processes and that the thyroid state affects only the mechanisms responsible for the contractile recovery of rat myocardium. The modifications induced by thyroid dysfunction on contractile recovery might be accounted for by an effect of thyroid state on a time-dependent recycling of calcium by the sarcoplasmic reticulum.
Biochemical kinetics of porcine cardiac subfragment-1.
Authors: Stein L A , White M P
Published: June 2012

The actin binding and ATPase kinetics of cardiac myosin subfragment-1 were compared with prior studies on skeletal myosin subfragments. Previous kinetic studies on rabbit skeletal subfragment-1 (S-1) have revealed two important features of the actomyosin ATPase activity. First, hydrolysis of ATP by myosin subfragment-1 proceeds both when S-1 is bound to actin and when it is dissociated from actin. Second, the actin concentration required to reach half the maximum ATPase activity, Ka(ATPase), is considerably lower than the actin concentration required to bind half the subfragment-1 during steady state hydrolysis of ATP, Ka(binding). These kinetic facts require that skeletal myosin hydrolyze ATP without dissociating from actin; therefore, a "nondissociating" pathway for ATP hydrolysis exists. The studies reported here show that porcine cardiac S-1 is very similar to rabbit skeletal S-1. Under identical conditions to prior work on skeletal S-1, the Ka(ATPase) of porcine cardiac S-1 is approximately equal to that reported for skeletal S-1. This is also true for Ka(binding). Comparison of Ka(ATPase) and Ka(binding) shows that for cardiac proteins Ka(ATPase) is fourfold to sixfold stronger than Ka(binding), i.e., half maximal ATPase activity is achieved at about one fifth the actin necessary to reach 50% binding. The extrapolated maximum ATPase activity at saturating actin concentration for cardiac S-1 is consistently slower than skeletal S-1 by about a factor of 2.5. Furthermore, studies of the actoS-1 ATPase activity at high actin concentrations as well as with crosslinked actoS-1 show no significant inhibition, implying the requirement of a "nondissociating" pathway for ATP hydrolysis by cardiac myosin subfragment-1.
Effects of hypoxia, hyperkalemia, and metabolic acidosis on canine subendocardial action potential conduction.
Authors: Veenstra R D , Joyner R W , Wiedmann R T , Young M L , Tan R C
Published: June 2012

We have studied the individual and combined effects of elevated external potassium concentration (8 mM [K+], metabolic acidosis (pH = 6.8), and hypoxia at different stimulation 400 milliseconds) on Purkinje (P) and ventricular (V) conduction velocities and on Purkinje-ventricular junctional conduction delay (PVJ delay) in in vitro preparations from canine ventricles. Elevated [K+] had opposite effects on P and V velocities, increasing V velocity by 8% while reducing P velocity by 7%. Acidosis reduced P velocity by 9% while reducing V velocity by only 4%. Hypoxia and rapid stimulation rates had no significant effect on either P or V velocities. All test solutions (except hypoxia alone) significantly increased the PVJ delay. The magnitude of the increase in PVJ delay was much greater than the effects on either P or V velocity. In addition, hypoxia and rapid stimulation augmented the increase in PVJ delay in the presence of elevated [K+] and/or acidosis. The special features of conduction at the PV junctional sites may produce altered pathways of excitation of the ventricles during myocardial ischemia.
Effects of procaine on pharmaco-mechanical coupling mechanisms activated by acetylcholine in smooth muscle cells of porcine coronary artery.
Authors: Ueno H , Sumimoto K , Hashimoto T , Hirata M , Kuriyama H
Published: June 2012

The action of procaine on pharmaco-mechanical coupling activated by application of acetylcholine (ACh) was investigated using collagenase-treated dispersed intact and skinned smooth muscle cells and intact muscle tissues of the porcine coronary artery. ACh reduced stored 45Ca2+, and this action was prevented by procaine in intact dispersed cells. The maximum reduction in the level of stored 45Ca induced by caffeine (25 mM) or inositol 1,4,5-trisphosphate (InsP3; 3 microM) was also prevented by procaine in the skinned muscle cells in the presence or absence of ATP. However, inhibitions of the latter required higher concentrations of procaine than the former. Release by 10 microM ACh of Ca2+ from its store site in the presence or absence of extracellular Ca2+ was also inhibited by procaine and was detected using the quin2 fluorescence method. In these smooth muscle tissues, ACh (above 10 nM) reduced the amount of phosphatidylinositol 4,5-bisphosphate (PI-P2) and dose dependently increased the amount of phosphatidic acid. Procaine inhibited the hydrolysis of PI-P2 activated by ACh, thus reducing the amount of InsP3 and the release of Ca2+ from the store site. It is concluded that procaine has multiple actions on the porcine coronary artery, and one of the actions related with pharmacomechanical coupling appears through inhibition of hydrolysis of PI-P2 induced by ACh.
Contributions of intracellular and extracellular Ca2+ pools to activation of myosin phosphorylation and stress in swine carotid media.
Authors: Ratz P H , Murphy R A
Published: June 2012

Contractile agonists can mobilize Ca2+ from both intracellular and extracellular stores in smooth muscle. This study addresses the role of Ca2+ mobilization as it relates to the complex manner by which Ca2+ regulates the contractile system in smooth muscle. In swine carotid media, both histamine and phenylephrine produced initial rapid increases in myosin phosphorylation and stress. Stress was sustained for the duration of the stimulus while myosin phosphorylation slowly declined to steady-state levels. Removal of extracellular Ca2+ or elimination of cellular Ca2+ influx did not dramatically reduce the initial rapid increase in myosin phosphorylation produced by either agonist but reduced steady-state levels of myosin phosphorylation to basal values. Initial rapid increases in stress were seen, but stress was not maintained. Following depletion of Ca2+ from sarcoplasmic reticulum, muscle activation by Ca2+ influx in the presence of phenylephrine occurred without an initial transient in myosin phosphorylation, and stress developed slowly. Steady-state levels of myosin phosphorylation and stress were not different from control values. Similar results were obtained with histamine, although a small transient in myosin phosphorylation was also seen. These results are consistent with the hypothesis that the role of the sarcoplasmic reticulum in vascular smooth muscle is to provide high myoplasmic Ca2+ concentrations causing extensive myosin phosphorylation and rapid crossbridge cycling leading to rapid stress development. In the presence of extracellular Ca2+, control levels of agonist-induced steady-state stress and myosin phosphorylation could be produced without an initial phosphorylation transient when intracellular Ca2+ pools were depleted, suggesting that the sarcoplasmic reticulum is not required for the regulation of steady-state myoplasmic [Ca2+] during "latch".