bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Emotional and Physical Stimuli on Pressure in the Isolated Vein Segment
Authors: MARTIN DAN A. , WHITE KERR L. , VERNON CHARLES R.
Published: June 2012

Generalized alterations in venous tone may shift large amounts of blood within the vascular system. Both physical and emotional stimuli are capable of affecting venous tone. The present report is a study in healthy males of the effects of certain of these factors on pressure (tone) in a peripheral vein segment isolated by means of specially designed, Plexiglas vein occluders. The emotional stimuli employed were the most effective of the group in increasing venous tone.
Estimation of Cardiac Output from Precordial Dilution Curves in Patients with Cardiopulmonary Disease
Authors: SCHREINER BERNARD F. , LOVEJOY FRANK W. , YU PAUL N. , SURAN MAGRUDER MRS. , RUTH KNIGHT MRS.
Published: June 2012

Comparison of flow rates measured from precordial dilution curves, simultaneous direct arterial dilution curves, and nearly simultaneous Fick determinations in 29 patients failed to indicate any difference in precision. Successive precordial determinations of flow rate were adequately reproducible. It is concluded that the precordial dilution method gives flow values comparable to those obtained by other, more laborious methods.
Effect of Anticoagulants on Recanalisation
Authors: TAYLOR ALEXANDER , ESSEX HIRAM E.
Published: June 2012

Reports have appeared stating that the time required for recanalisation of a vessel occluded by an experimental thrombus is decreased when an anticoagulant of the coumarin variety is administered. The experiments described here were undertaken to verify such reports.
A Continuous Cardiac Output Recorder Employing the Fick Principle
Authors: GUYTON ARTHUR C. , CHARLES A. FARISH , J. BERRY ABERNATHY
Published: June 2012

A continuous cardiac output recorder has been developed utilizing an oxygen consumption recorder, an arteriovenous oxygen difference recorder and a computer. The computer continuously derives and records the cardiac output by dividing the rate of oxygen consumption by the A-V oxygen difference. Calibration of the continuous cardiac output recorder against a Ludwig stromuhr showed that under many different conditions and many different levels of cardiac output the 305 individual calibration points had a mean deviation from the regression line of ± 7.7 per cent. This correlation is as satisfactory as previously reported correlations between the intravenous dye method for recording cardiac output and the direct Fick method.
Effects of Aortic Insufficiency on Circulatory Dynamics of the Dog
Authors: WEST JAMES W. , WENDEL HERBERT , FOLTZ ELWOOD L.
Published: June 2012

In dogs with chronic aortic insufficiency accompanied by cardiac hypertrophy, the coronary blood flow, cardiac oxygen consumption, coronary arteriovenous oxygen difference, coronary oxygen utilization, systolic pressure and cardiac rate are increased significantly above the normals, while coronary venous oxygen saturation, coronary resistance and diastolic pressure are significantly decreased.
Alteration of Cholesterol Metabolism in the Rat with Linoleic Acid
Authors: MERRILL JOSEPH M.
Published: June 2012

When linoleic acid is added to the diet of the rat there is an average increase in incorporation of radiocarbon into liver cholesterol of 259 per cent. By contrast, the addition of coconut oil to the diet does not increase the incorporation of radiocarbon into liver cholesterol. The addition of linoleic acid to a stock diet is associated with an increased fecal excretion of Liberman-Burchard chromogens, 3-β-hydroxy sterols and bile acids.
Transmural Ventricular Pressures in Experimental Cardiac Tamponade
Authors: FOWLER NOBLE O. , SHABETAI RALPH , BRAUNSTEIN JOHN R.
Published: June 2012

Experimental cardiac tamponade was produced in open-chest dogs. Left and right ventricular systolic pressures fell when intrapericardial pressure was increased only a few millimeters of mercury. Negative diastolic transmural pressures of 1 to 6 mm. Hg developed in the left ventricle and negative diastolic transmural pressures of 2 to 8.5 mm. Hg developed in the right ventricle. In some instances the period of right ventricular systolic ejection was greatly abbreviated at higher levels of intrapericardial pressure.
Cerebral Hemodynamics of Experimental Cerebral Embolization
Authors: ROBIN EUGENE D. , FOWLER FRED , WHALEY ROBERT D. , CRUMP CHARLES H.
Published: June 2012

Cerebral embolization in anesthetized dogs produces a fall in cerebral blood flow but no significant increase in cerebrovascular resistance. The mechanism of the decreased flow is usually a decrease in mean arterial blood pressure. Section of the sympathetic-vagus trunks produces no consistent increase in cerebral blood flow or fall in cerebrovascular resistance.
Regression Studies with Safflower Oil and Sitosterol in Rabbit Atherosclerosis
Authors: MILLER JONATHAN P. , LAMBERT G. FREDERICK , FROST DOUGLAS V.
Published: June 2012

Hypercholesteremia with atherosclerosis was induced in male rabbits by feeding hydrogenated coconut oil as the only lipid in a purified diet. Replacing the hydrogenated coconut oil by safflower oil produccd a profound fall in plasma cholesterol in rabbits. Supplementing the safflower oil with βsitosterol at 3 per cent of the oil weight caused an even greater decrease in plasma cholesterol. Although in both cases the further development of aortic atheroma was arrested, there was no detectable regression of existing lesions, over 24 weeks. Hydrogenated coconut oil feeding produced high plasma and liver cholesterol levels in rabbits. When small amounts of safflower oil were fed in addition to the hydrogenated coconut oil, the elevation of plasma or liver cholesterol was much less.
Indicator Dilution in an Atrioventricular System with Competent or Incompetent Valves
Authors: McCLURE JOSEPH A. , LACY WILLIAM W. , LATIMER PAUL , NEWMAN ELLIOT V.
Published: June 2012

A mathematical analysis of the pumping action of a two-chambered system has been used to develop formulas describing the changes with time in the mass and concentration of an indicator in either chamber of such a system analogous to the atrium and ventricle with either competent or incompetent valves. Such formulas show how the parameters of a system control the shape of an indicator-dilution curve. From these formulas expressions were developed which permit the analysis of the system from an indicator-dilution curve. The theory was then used to analyze dilution curves produced by a model of known parameters.
Persistence of Abnormally High Vascular Tone in Vessels of the Finger after Digital Nerve Block in Patients with Chronic High Blood Pressure
Authors: GASKELL P. , DIOSY A.
Published: June 2012

The critical opening pressure of vessels supplying the nailfold capillaries of the finger was estimated as an index of the force being exerted by vascular smooth muscle in normal subjects and patients with various kinds of hypertension after the digital nerves were blocked. It was greater in the hypertensive patients, suggesting the existence of an abnormally high force being exerted by the smooth muscle in hypertensive patients which is not under the immediate control of the nervous system.
Computer Analysis of Arterial Properties
Authors: STACY RALPH W. , GILES FRED M.
Published: June 2012

Use of an analog computer for determination of mechanical properties of the arterial bed is described. This approach involves mathematical operations on a recorded central pulse to produce a computed peripheral pulse and computer parameters varied until matching is accomplished. Values for arterial elasticity, etc. are calculated from the computer settings.
Circulation in the Three-Chambered Snake Heart
Authors: JOHANSEN KJELL
Published: June 2012

Our knowledge on the physiologic evolution of the cardiovascular system is fragmentary. The reptiles and the snakes in particular represent a stage where our knowledge is especially poor. The present study deals with the circulatory dynamics of the snake heart. It may be suggested that the snake heart effectively prevents extensive mixing of arterial and venous blood. The durations of ventricular filling and contraction differ greatly from that in the mammalian heart.
Physiologic Changes during Chronic Congestive Heart Failure in Dogs with Tricuspid Insufficiency and Pulmonic Stenosis
Authors: YANKOPOULOS NICHOLAS A. , DAVIS JAMES O. , MCFARLAND JAMES A. , HOLMAN JOHN , CASPER ALFRED
Published: June 2012

chronic congestive heart failure was studied in dogs with surgically-produced tricuspid insufficiency and pulmonic stenosis. Ascites formed in association with an elevation in mean right atrial pressure. The volume of ascitic fluid and the rate of urinary sodium excretion varied greatly in individual dogs during the course of congestive failure and among the different animals. Sodium retention was most common but periods of sodium balance and natriuresis occurred. Comparative data on the right and left ventricles were obtained from determinations of intracardiac pressures, measurements of ventricular muscle mass at the time of sacrifice and studies of the lungs for evidence of chronic passive congestion. There was significant right ventricular hypertrophy but no evidence of left ventricular hypertrophy or failure.
Myogenic Nature of Increase in Intestinal Vascular Resistance with Venous Pressure Elevation
Authors: JOHNSON PAUL C. , GRAHAM L. STUART
Published: June 2012

These studies attempted to distinguish between the various intrinsic mechanisms which might be responsible for the increase in vascular resistance seen in the intestine with venous pressure elevation (the venous-arteriolar response). Intra-arterial infusion of procaine did not block the response, indicating that a local reflex is not involved. However, the resistance increase was greatly modified during infusion of a smooth muscle relaxant (papaverine). Cyanide and ischemia were more effective than papaverine, resistance remaining unchanged as venous pressure was elevated. The tone of the intestinal wall was not increased with venous pressure elevation. In preparations perfused with an oil-kerosene mixture, resistance decreased as venous pressure was elevated, although intravascular and extravascular fluid accumulation was quantitatively the same as in the blood-perfused control. It is concluded that the venous-arteriolar response is not dependent upon neural mechanisms, nor is it due to purely physical factors. It is suggested that elevation of venous pressure causes sufficient increase of arteriolar pressure to induce a myogenic response of the resistance vessels.
Smooth muscle tone and rapid resetting of rat aortic baroreceptors.
Authors: Andresen M C , Yang M
Published: June 2012

Changes in conditioning mean arterial pressure (cMAP) selectively alter the set point of arterial baroreceptors and baroreflexes without affecting gain. Changes in smooth muscle tone at constant cMAPs shift the pressure-discharge curves of aortic baroreceptors in a similar manner. Using an in vitro preparation of the rat aortic arch, we tested whether near maximal changes in smooth muscle tone affect rapid resetting in single regularly discharging aortic baroreceptors. Discharge, pressure, and aortic diameter were simultaneously measured. By using vasoactive drugs (phenylephrine, angiotensin II, Bay K 8644, and nitroprusside), rapid resetting to cMAP changes was tested during different smooth muscle tone conditions (control, constricted, and dilated). Baroreceptor discharge-response curves were periodically assessed with slow ramps of increasing pressure at each of three different cMAP levels (10-15 minutes each). Rapid resetting relations were constructed for pressure threshold (Pth) and diameter threshold (Dth) plotted against cMAP and conditioning diameter (cD), respectively. Vasoconstriction decreased Pth in all baroreceptors (n = 13, p less than 0.05). Baroreceptor resetting ability as indicated by the slopes of the resetting relations (pressure- or diameter-resetting ratios, delta Pth/delta cMAP or delta Dth/delta cD, respectively) was unaffected by large increases in smooth muscle tone (p greater than 0.12). Vasoconstriction, however, offset the pressure-resetting relation, shifting the linear relation in a parallel manner to higher Pth values. In contrast, Dth values during vasoconstriction were not offset but instead fell along a single diameter-resetting relation coincident with the control relation for each baroreceptor. This last result suggests that acute alteration of vessel mechanics by vasoconstriction does not alter the basic rapid resetting process.(ABSTRACT TRUNCATED AT 250 WORDS)
Reversibility of the effects of normothermic global ischemia on the ryanodine-sensitive and ryanodine-insensitive calcium uptake of cardiac sarcoplasmic reticulum.
Authors: Davis M D , Lebolt W , Feher J J
Published: June 2012

The effect of normothermic ischemia and ischemia/reperfusion on the function of cardiac sarcoplasmic reticulum (CSR) was investigated using a modified Langendorff perfusion of isolated rat hearts. The function of the CSR was assessed by the oxalate-supported Ca2+ uptake rate of ventricular homogenates. The contribution of the ryanodine-sensitive portion of the CSR was determined by using 20 microM ruthenium red or 625 microM ryanodine to close the CSR Ca2+ release channel. The Ca2+ uptake rate of the CSR decreased progressively with increasing duration of ischemia, but this depression was much less when uptake was assayed in the presence of ryanodine. The depression in CSR Ca2+ uptake preceded ischemic contracture. Ryanodine and ruthenium red stimulated uptake almost equally in control hearts, but ruthenium red was much less effective than ryanodine after ischemia. This difference could not be overcome by increasing the ruthenium red concentration. These results confirm the suggestion that the Ca2+ release channel is inappropriately opened after ischemia. The CSR uptake rates were almost completely restored at 15 minutes of reperfusion after 5 and 10 minutes of ischemia but were only partially restored after 15 minutes of ischemia. At reperfusion, mechanical function (end-diastolic pressure and peak systolic developed pressure) was markedly depressed after only 15 minutes of ischemia. The degree of "stunning" correlated well with the depression of CSR function in individual hearts. The decreased Ca2+ uptake of the CSR was not due to a buildup of ADP in the homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinetics of restitution of left ventricular relaxation.
Authors: Prabhu S D , Freeman G L
Published: June 2012

Although the kinetics of cardiac systolic force restitution have been well described, the restitution kinetics of left ventricular relaxation have not been examined. To define relaxation restitution behavior, we studied seven dogs chronically instrumented with left ventricular high-fidelity micromanometers and piezoelectric dimension crystals. After a priming period at a basic cycle length of 375 msec, test extrastimuli were introduced after a range of extrasystolic intervals (ESIs). Relaxation behavior of control and extrasystolic beats was characterized by the time constant of isovolumic relaxation, tau. Relaxation restitution can be described by two concatenated monoexponential curves, an early phase described by a rapid time constant and a late phase described by a slower time constant (TC1, 36.21 +/- 7.90 msec; TC2, 75.94 +/- 10.65 msec; p less than 0.05). The first phase of relaxation restitution parallels systolic force restitution over the same range and displays faster recovery (TCs, 58.93 +/- 10.01 msec, p less than 0.05). Postextrasystolic restitution of test pulses after beats at fixed ESIs depends on the initial ESI. Relaxation recovery of postextrasystolic beats proceeds faster with smaller initial ESIs (TC1 for ESI of 300 msec, 13.27 +/- 4.05 msec; TC1 for ESI of 450 msec, 72.85 +/- 21.72 msec; p less than 0.0001). The monoexponential pattern of restitution was seen with model-independent descriptors of relaxation as well as with tau.
Expression and pharmacological characterization of a stimulatory subtype of adenosine receptor in fetal chick ventricular myocytes.
Authors: Xu D , Kong H Y , Liang B T
Published: June 2012

Ventricular and atrial myocytes cultured from chick embryos 14 days in ovo were used as model systems to study cardiac adenosine receptors. In membranes of ventricular cultures, blocking of the A1-adenosine receptor pathway by the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or by pertussis toxin treatment of the myocyte resulted in a significant adenosine agonist-mediated stimulation of the adenylate cyclase activity. The maximal increases in adenylate cyclase activity caused by the equipotent or the A2-adenosine receptor-selective agonists (from 52.1 +/- 3% to 63 +/- 10% [mean +/- SEM]) were significantly greater than those caused by the A1-selective agonists (from 11 +/- 5% to 34.6 +/- 7%) (p less than 0.01, by t test, n = 4-8). However, in membranes of atrial myocytes, when A1-subtype had been blocked, the various adenosine agonists had no effect on the adenylate cyclase activity. Whether the stimulatory adenylate cyclase-coupled adenosine receptor is also capable of stimulating contractility in the intact ventricular myocyte was next investigated. In ventricular but not in atrial cells, the various adenosine agonists caused an increase in the contractile amplitude in the presence of DPCPX or in myocytes preexposed to pertussis toxin. The increase in contraction amplitude caused by each agonist was expressed as percent of maximum (maximum is the increase in contractility caused by 2.4 mM calcium). In the pertussis toxin-treated myocyte, the maximal increases caused by the equipotent or A2-agonists (NECA, MECA, CV-1808, and CGS21680, from 49.6 +/- 3% to 52.5 +/- 6%, n = 8-12) were significantly greater than those elicited by the A1-agonists (2-CADO, S-PIA, R-PIA, and DCCA, from 12 +/- 4% to 37 +/- 3%, n = 8) (p less than 0.05, by t test). These data demonstrated that a stimulatory adenosine receptor, likely the A2-adenosine receptor, was present on the ventricular but not the atrial myocytes and was linked directly to a stimulation of the cardiac contractility. The functional effects mediated by the A1-subtype became manifested in the presence of isoproterenol, as evidence by an inhibition of the isoproterenol-stimulated increases in adenylate cyclase activity and in cardiac contractility by adenosine agonists. Thus, both subtypes of adenosine receptors, each mediating opposing responses, were present on the ventricular myocytes, whereas only the A1-subtype was found in the atria. The presence of a stimulatory functional A2-adenosine receptor may help explain the absence of a direct negative inotropic response to adenosine in the ventricle.
JE mRNA accumulates rapidly in aortic injury and in platelet-derived growth factor-stimulated vascular smooth muscle cells.
Authors: Taubman M B , Rollins B J , Poon M , Marmur J , Green R S , Berk B C , Nadal-Ginard B
Published: June 2012

The early response to vascular injury is characterized by migration of inflammatory cells, including monocytes, and platelets to the damaged vessel wall. These inflammatory cells may serve as a source of growth factors and cytokines that stimulate vascular smooth muscle cell (VSMC) migration and proliferation associated with intimal hyperplasia. JE is a platelet-derived growth factor (PDGF)-inducible "early" gene that encodes a monocyte chemoattractant and, as such, could play an important role in inflammation. We now report that JE mRNA levels are increased in intact aorta after balloon injury. The time course of this increase, with maximal levels at 4 hours, is similar to that seen in PDGF-treated cultured rat aortic VSMCs. The accumulation of JE mRNA in cultured VSMCs is accompanied by a marked increase in the secretion of JE protein. The elevation of JE mRNA levels in VSMCs shows specificity for PDGF, because angiotensin II, alpha-thrombin, and epidermal growth factor fail to increase JE mRNA levels. In contrast to 3T3 fibroblasts, the accumulation of JE mRNA in VSMCs in response to PDGF is predominantly due to an increase in JE mRNA stability. The accumulation of JE mRNA in VSMCs stimulated by PDGF appears to occur via a novel pathway(s) independent of Ca2+ mobilization, Na(+)-H+ exchange, protein kinase C activation, or elevation in cAMP levels. These findings suggest that VSMCs may take part in the early inflammatory response after injury through the production of JE, a potent monocyte chemoattractant. Finally, our data suggest that JE may be a marker for PDGF-specific effects on VSMCs, both in vitro and in vivo. Thus, in addition to direct effects on VSMC growth and migration, PDGF may play a role in the early inflammatory response after vascular injury by inducing chemoattractants, such as that encoded by JE.
Effect of a cigarette smoke extract on the metabolism of the proinflammatory autacoid, platelet-activating factor.
Authors: Miyaura S , Eguchi H , Johnston J M
Published: June 2012

Cigarette smoking is associated with an increased incidence of a number of diseases. Minimal information is available at the molecular level concerning the mechanism of action of cigarette smoke. Platelet-activating factor (PAF) is one of the most potent proinflammatory agents described. PAF concentration may be regulated by the degradation of PAF as catalyzed by the plasma enzyme, PAF acetylhydrolase (PAF-AH). This enzyme is associated with the lipoprotein fraction. The exposure of low density lipoprotein to a cigarette smoke extract (CSE) has been shown to alter the charge of low density lipoprotein and its uptake by macrophages. The activity of PAF-AH in the lipoprotein fraction has been assayed after exposure to CSE. The activity of PAF-AH was inhibited by the CSE in a dose-dependent manner. The inhibition of PAF-AH by the CSE was not altered by superoxide dismutase or catalase addition. Sulfhydryl compounds prevented and reversed the inhibition of PAF-AH caused by CSE. The inhibitor present in CSE was not nicotine, its major metabolic product, (-)-cotinine, or several compounds known to be present in the extract. The charge alteration reaction(s) and PAF-AH inhibition appear to be localized at different sites of the lipoprotein molecule. The observed inhibition may account for the increase in the plasma PAF concentration that is known to occur in smokers. The increase of PAF may contribute to the increased incidence of cardiovascular and lung diseases known to be present in smokers.
Vascular responses to activated leukocytes after regression of atherosclerosis.
Authors: Padgett R C , Heistad D D , Mügge A , Armstrong M L , Piegors D J , Lopez J A
Published: June 2012

Activation of leukocytes in vivo produces marked constriction of large arteries in atherosclerotic, but not in normal, monkeys. We tested the hypotheses that vasoconstrictor responses to activated leukocytes in vivo may be abnormal during hypercholesterolemia before the development of atherosclerotic lesions and that responses may return to normal after the regression of atherosclerosis. Leukocytes were activated by injection of the chemotactic peptide formyl-methionine-leucine-phenylalanine (fMLP) into the blood-perfused hind limb of four groups of cynomolgus monkeys: monkeys fed a normal diet (normal group, n = 18), monkeys fed an atherogenic diet for 3-4 months (hypercholesterolemic group, n = 6), monkeys fed an atherogenic diet for 20 months (atherosclerotic group, n = 19), and monkeys fed an atherogenic diet for 18 months, followed by a normal diet for 20 months (regression group, n = 14). Baseline resistance of large arteries was 1.5 +/- 0.2 (mean +/- SEM), 2.0 +/- 0.6, 3.5 +/- 0.4 (p less than 0.05 versus normal), and 1.7 +/- 0.2 mm Hg/ml/min per 100 g tissue for the normal, hypercholesterolemic, atherosclerotic, and regression groups, respectively. Injection of fMLP did not change resistance of large arteries in normal or hypercholesterolemic monkeys. Injection of fMLP increased resistance of large arteries by 3.0 +/- 0.7 mm Hg/ml/min per 100 g tissue in atherosclerotic monkeys and by 1.3 +/- 0.4 mm Hg/ml/min per 100 g tissue in regression monkeys (p less than 0.05 versus atherosclerotic and normal). Thus, abnormal vasoconstriction in response to activation of leukocytes persists, but to a lesser extent, after regression. In contrast, vasoconstrictor responses to serotonin, which were potentiated in atherosclerotic monkeys, were normal after regression.(ABSTRACT TRUNCATED AT 250 WORDS)
L- and T-type Ca2+ channels in canine cardiac Purkinje cells. Single-channel demonstration of L-type Ca2+ window current.
Authors: Shorofsky S R , January C T
Published: June 2012

Canine cardiac Purkinje cells contain both L- and T-type calcium currents, yet the single Ca2+ channels have not been characterized from these cells. Additionally, previous studies have shown an overlap between the steady-state inactivation and activations curves for L-type Ca2+ currents, suggesting the presence of L-type Ca2+ "window" current. We used the on-cell, patch-clamp technique to study Ca2+ channels from isolated cardiac Purkinje cells. Patches contained one or more Ca2+ channels 75% of the time. L-type channels were seen in 69% and T-type channels in 73% of these patches. With 110 mM Ba2+ as the charge carrier, the conductances of the L- and T-type Ca2+ channels were 24.2 +/- 0.8 pS (n = 9) and 9.0 +/- 0.5 pS (n = 8), respectively (mean +/- SEM). With 110 mM Ca2+ as the charge carrier, the conductance of the L-type Ca2+ channel decreased to 9.7 +/- 1.2 pS (n = 4), whereas the T-type Ca2+ channel conductance was unchanged. Voltage-dependent inactivation was shown for both L- and T-type Ca2+ channels, although for L-type Ca2+ channel with Ba2+ as the charge carrier, inactivation took at least 30 seconds at a potential of +40 mV. After channel inactivation was complete, L-type Ca2+ channel reopenings were observed following repolarizing steps into the window voltage range. Thus, our data identify both L- and T-type Ca2+ channels in cardiac Purkinje cells and demonstrate, at the single-channel level, L-type channel transitions expected for a window current. Window current may play an important role in shaping the action potential and in arrhythmogenesis.
Implementation and evaluation of a two-compartment model for quantification of myocardial perfusion with rubidium-82 and positron emission tomography.
Authors: Herrero P , Markham J , Shelton M E , Bergmann S R
Published: June 2012

Positron emission tomography offers the ability to noninvasively assess regional myocardial perfusion in absolute terms (i.e., milliliters per gram per minute). Accurate estimates have been difficult to achieve with generator-produced 82Rb because of the complex behavior of this tracer in the myocardium. The aim of the present study was to determine whether regional myocardial blood flow could be assessed quantitatively with 82Rb and positron emission tomography by using a two-compartment kinetic model. Regional perfusion in milliliters per gram per minute was estimated from dynamic tomographic scans after intravenous administration of 82Rb in 18 studies in 13 intact dogs studied without intervention, after 2 and 24 hours of induced ischemia, during reperfusion after transient occlusion, or at rest and after pharmacological hyperemia after induced coronary artery stenosis. Regional flow was estimated along with the forward and backward rates of transport (k1 and k2 [minutes-1]) after the relative volume of distribution of the first compartment was fixed to 0.53 ml/ml and the tomographic parameters, the recovery and spillover fractions, were fixed to averaged values obtained in previous studies. In 36 comparisons, estimates of regional flow with 82Rb correlated well with flow measured with concomitantly administered radiolabeled microspheres (r = 0.91, p less than 0.05) over the flow range from 0.14 to 4.25 ml/g/min. A putative index of viability, k2, increased significantly in regions with severe ischemia. The results suggest that quantification of regional myocardial perfusion is possible in centers using 82Rb for estimates of myocardial perfusion when a physiologically appropriate, two-compartment model is used.
Developmental changes in membrane Ca2+ and K+ currents in fetal, neonatal, and adult rabbit ventricular myocytes.
Authors: Huynh T V , Chen F , Wetzel G T , Friedman W F , Klitzner T S
Published: June 2012

Whole-cell calcium current (ICa) and inwardly rectifying potassium current (IK1) were studied in 21-day fetal, 28-day fetal (total gestation, 31 days), 2-5-day neonatal, and adult rabbit ventricular myocytes isolated by enzymatic dissociation. Whole-cell peak ICa and IK1 at -100 mV increased significantly after birth. Cell size approximated from cell membrane capacitance also increased with age, with the most significant increase occurring after birth. When normalized to cell surface area, peak ICa density increased from day 21 of gestation to the neonate and then increased again from neonate to adult. In all age groups, peak ICa occurred at a test potential of +10 mV, and the shape of the Ca2+ current-voltage relation did not change with age. These findings suggest that there are no significant developmental changes in the voltage dependence of ICa. Therefore, the measured age-related increase in Ca2+ current density may result from increased channel expression. IK1 also exhibited a pattern of increasing current density with age. For IK1, the increase in current density was most rapid between day 21 and the perinatal period and much slower after birth. These results demonstrate that ICa and IK1 undergo significant changes during late fetal and postnatal development.
Power-afterload relation in the failing human ventricle.
Authors: Chiu Y C , Arand P W , Carroll J D
Published: June 2012

Animal studies have shown that the power output of the left ventricle is related to afterload by a bell-shaped curve. Furthermore, the normal ventricle operates at the maximum power point, whereas the diseased ventricle operates off the maximum power point because of increased afterload. We studied this relation in eight patients with dilated cardiomyopathy. A high-fidelity catheter with micromanometer pressure and electromagnetic velocity transducers was used to measure blood pressure and flow velocity in the ascending aorta. The latter was converted into volumetric flow by calibrating with the simultaneously determined thermodilution cardiac output. Ventricular power was calculated by dividing the integral of the aortic blood pressure-flow product by the duration of the cardiac cycle. Intravenous nitroprusside was used to alter afterload and the power-afterload relation was obtained by plotting power against mean aortic blood pressure. In all patients, as blood pressure was lowered initially, the power output of the left ventricle increased. As the dose of nitroprusside was increased further, the total power either plateaued or actually decreased. The averaged power and the mean blood pressure at control were 1.00 +/- 0.62 W and 92 +/- 9.3 mm Hg, respectively. The averaged maximum increase in power with nitroprusside was 22%, to 1.22 +/- 0.73 W, and this occurred at a mean pressure of 80 +/- 8.8 mm Hg. This study showed that the power-afterload relation in the human ventricle has a maximum power point at some intermediate level of afterload, similar to that found in animal studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased heart rate prevents the isomyosin shift after cardiac transplantation in the rat.
Authors: Geenen D L , Malhotra A , Buttrick P M , Scheuer J
Published: June 2012

The heterotopically transplanted rat heart undergoes significant atrophy and a shift from V1 to V3 isomyosin. The purpose of this study was to pace the cardiac isograft and determine whether an increase in heart rate would attenuate the changes in cardiac mass and isoenzyme distribution. Nonpaced transplanted hearts were compared with hearts in which pacing was initiated at 7 Hz, 24 hours after transplantation, and continued for 7 days. There was a 29% decrease in myosin ATPase activity and a 22% decrease in alpha-myosin in the nonpaced isograft; both decreases were completely prevented by pacing. The decrease in cardiac mass was also significantly attenuated. Pacing did not alter intrinsic heart rate, systolic pressure, dP/dt, or norepinephrine concentration in the isograft. These results suggest that the adaptation in both cardiac mass and isoenzymes may be related to the rate or the rate-pressure product in the transplanted paced heart independent of left ventricular pressure, tissue catecholamines, or neural activity.
Cryoblockade in limbic brain (amygdala) prevents or delays ventricular fibrillation after coronary artery occlusion in psychologically stressed pigs.
Authors: Carpeggiani C , Landisman C , Montaron M F , Skinner J E
Published: June 2012

Neomammalian and paleomammalian (limbic) brain structures control different behaviors and the autonomic support specific to each. Both neural systems are involved in cardiovascular disorders. Our previous studies showed that bilateral cryoblockade of a neomammalian structure (the frontal lobes) reduces blood pressure elevations in experimental hypertension and prevents lethal arrhythmogenesis in experimental myocardial infarction. Other studies showed that bilateral lesions in a paleomammalian structure (amygdala) also reduce the blood pressure elevations. Thus, we hypothesized that cryoblockade of the amygdala would prevent lethal arrhythmogenesis. We found that cooling of cryoprobes implanted bilaterally in the amygdala prevented ventricular fibrillation in five of eight pigs during a 20-minute period of reversible myocardial ischemia, whereas cryoblockade in structures surrounding the amygdala (five pigs), unilateral cryoblockade in the amygdala (two pigs), or sham operations (three pigs) did not prevent ventricular fibrillation (p less than 0.003). In two of the five pigs with amygdaloid blockade, the cooling was reversed at 20 minutes while the coronary occlusion continued (24 hours), and still ventricular fibrillation did not occur. In all other cases, ischemia was reversed at 20 minutes so that the heart could recover; this enabled histochemical documentation that the heart was normal at the time(s) ischemia was induced, and it allowed within-subject control experiments. Amygdaloid cryoblockade produced a small but significant increase in heart rate (10 beats per minute) without a change in blood pressure. We conclude that the paleomammalian brain, like its neomammalian counterpart, mediates brain effects on fatal arrhythmogenesis.
Regulation of acetylcholinesterase in avian heart. Studies on ontogeny and the influence of vagotomy.
Authors: Jo S A , Higgins D M , Berman H A
Published: June 2012

This article examines the role of innervation in regulating expression of acetylcholinesterase (AchE), butyrylcholinesterase (BuchE), and the muscarinic acetylcholine receptor (mAchR) in avian heart. Two distinct approaches are taken. The first approach examines the relation between the onsets of parasympathetic and sympathetic innervation and the appearance of AchE and BuchE. All molecular forms of AchE and BuchE are present in early embryonic chick heart well before the onset of parasympathetic and sympathetic innervation. These molecular forms are characterized by sedimentation coefficients of 4.5S, 11S, 15S, and 19S. With further development, the amounts of AchE fall; the reductions in AchE parallel the onset of functional parasympathetic innervation. The amounts of BuchE increase progressively throughout embryonic development, independent of autonomic innervation, and in mature chick heart predominate over the much less abundant amounts of AchE. The 15S and 19S forms of AchE in heart are lost during early embryogenesis but reappear in skeletal muscle during later embryogenesis. The second approach examines the influence of vagotomy and sympathetic denervation of 8-day-old chick myocardium on expression of the molecular forms of AchE, BuchE, mAchR, and beta-adrenergic receptors. The amounts of AchE and BuchE molecular forms in avian heart are not measurably influenced by bilateral vagotomy for a duration of 4 days, unilateral vagotomy for a duration of 25 days, or sympathetic denervation. A measurable upregulation is observed in muscarinic receptors (35-46%) after vagotomy but not sympathectomy and in beta-adrenergic receptors (29%) after sympathectomy but not vagotomy. In all cases, results in atria and ventricles are nearly identical. The present results indicate that expression of AchE in the myocardium is unique and different from that in skeletal muscle and not directly linked with autonomic innervation.
Increased messenger RNA level of the inhibitory G protein alpha subunit Gi alpha-2 in human end-stage heart failure.
Authors: Eschenhagen T , Mende U , Nose M , Schmitz W , Scholz H , Haverich A , Hirt S , Döring V , Kalmár P , Höppner W
Published: June 2012

In human heart failure the positive inotropic and cAMP-elevating effects of both beta-adrenoceptor agonists and phosphodiesterase inhibitors are diminished. This has been explained at least in part by an increase in the inhibitory signal-transducing G protein (Gi) and unchanged stimulatory G protein (Gs). In the present study we determined the mRNA expression pattern of the alpha subunits of Gi-1, Gi-2, Gi-3, and Gs in myocardial tissue samples of patients undergoing heart transplantation. Northern blot analysis of total RNA extracted from left ventricles with 32P-labeled cDNAs demonstrated expression of Gi alpha-2, Gi alpha-3, and Gs alpha mRNA. In contrast, Gi alpha-1 mRNA was not detectable. To investigate whether the increased ratio of Gi/Gs might be due to altered gene expression, we compared mRNA levels of Gi alpha-2, Gi alpha-3, and Gs alpha in left ventricular myocardium from failing hearts with idiopathic dilated cardiomyopathy (n = 8) and ischemic cardiomyopathy (n = 6) and from nonfailing hearts from transplant donors (n = 8). Compared with nonfailing control hearts, the Gi alpha-2 mRNA was increased by 75 +/- 26% (p less than 0.05) in idiopathic dilated cardiomyopathy hearts and 90 +/- 26% (p less than 0.05) in ischemic cardiomyopathy hearts. Gi alpha-3 and Gs alpha mRNA levels were similar in the three groups. The results suggest that as in other mammalian species, Gi alpha-2 and Gi alpha-3 mRNA are the predominant Gi alpha mRNA subtypes in human ventricular myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of simulated ischemia and reperfusion on the sarcoplasmic reticulum of digitonin-lysed cardiomyocytes.
Authors: Hohl C M , Garleb A A , Altschuld R A
Published: June 2012

ATP-dependent, inorganic phosphate-supported 45Ca2+ uptake by digitonin-lysed adult rat ventricular cardiomyocytes was used to evaluate the effects of simulated ischemia and reperfusion on the physically intact sarcoplasmic reticulum. Mitochondrial reactions were inhibited with rotenone and oligomycin. 45Ca2+ accumulation in the presence of the calcium efflux inhibitors, procaine (10 mM) and ruthenium red (30 microM), was used to characterize unidirectional uptake kinetics. A decrease in pH from 7.2 to 6.6 increased the [Ca2+] K0.5 from 0.5 to 2.0 microM and reduced the apparent Vmax by 28%. In the absence of procaine and ruthenium red, at a free [Mg2+] of 0.5 mM, maximum net uptake occurred at pCa 6.2 when pH was 7.2 and at pCa 6.0 when pH was 6.6. At lower pCa, net Ca2+ accumulation declined. Increasing free [Mg2+] from 0.5 to 1 mM at pH 6.6 or to 2.5 mM at pH 7.2 increased net 45Ca2+ accumulation in the absence of procaine and ruthenium and shifted maximum uptake to pCa 5.6 and 6.0, respectively. Increases in cytosolic free [Mg2+] thought to occur during myocardial ischemia are therefore capable of inhibiting calcium efflux from the sarcoplasmic reticulum. Reducing [ATP] from 10 to 1 mM reduced maximum net 45Ca2+ uptake by 30% both in the presence and absence of efflux inhibitors. Preincubation of intact myocytes under conditions designed to simulate ischemia and reperfusion decreased 45Ca2+ uptake greater than or equal to 50%. The data indicate that myocardial ischemia and reperfusion can alter both Ca2+ accumulation and calcium release by the sarcoplasmic reticulum.
Specific receptor-guanine nucleotide binding protein interaction mediates the release of endothelium-derived relaxing factor.
Authors: Liao J K , Homcy C J
Published: June 2012

High affinity agonist-binding (HAB) sites are formed from specific receptor interaction with guanine nucleotide-binding (Gi) proteins. To determine whether the release of endothelium-derived relaxing factor (EDRF) is regulated by specific receptor-Gi protein coupling, we treated bovine aortic endothelial cells with 100 ng/ml pertussis toxin (PTX) for 16 hours to effect receptor-Gi protein uncoupling. The degree of receptor uncoupling as measured by the loss of HAB sites for the alpha 2-adrenergic receptor and bradykinin receptor was assessed by radioligand binding studies using partially purified bovine aortic endothelial cell membranes. The release of EDRF in response to UK14304 (an alpha 2-adrenergic receptor agonist) and bradykinin stimulation was measured with a bioassay apparatus. The Gi protein isoforms were characterized by Western blotting, and complete ADP-ribosylation of these proteins was confirmed by PTX-catalyzed [32P]NAD ribosylation. PTX produced a greater inhibition of EDRF release via the alpha 2-adrenergic receptor pathway compared with the bradykinin receptor pathway (80% versus 46%, p less than 0.01). This corresponded to the loss of HAB sites from the alpha 2-adrenergic receptor and bradykinin receptor pathway (72% versus 46%, p less than 0.01) as compared with complete loss of both HAB sites in the presence of GppNHp (0.1 mM). Since loss of HAB sites from PTX-mediated receptor uncoupling parallels the inhibition of EDRF release, these data suggest that Gi proteins contribute to a greater proportion of HAB sites derived from alpha 2-adrenergic receptor rather than bradykinin receptor interaction and that the inhibition of EDRF release by PTX is mainly due to the loss of these HAB sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of endothelin on plasma volume and albumin escape.
Authors: Zimmerman R S , Martinez A J , Maymind M , Barbee R W
Published: June 2012

Previous studies have demonstrated that endothelin-1 (ET-1) is a potent vasoconstrictor that decreases cardiac output and increases hematocrit. The present study was designed to determine if the rise in hematocrit and decrease in cardiac output are in part due to shifts of plasma from the vascular space to the interstitial space. Red blood cell volume and plasma volume were determined by using chromium-51-labeled erythrocytes and iodine-125-labeled albumin, respectively, in anesthetized, nephrectomized, splenectomized rats. The present study demonstrates that ET-1 increases mean arterial pressure and hematocrit. This effect is associated with an increase in total-body albumin escape, which is reflected by a marked reduction in whole-body plasma volume. ET-1 enhanced albumin escape primarily in the liver, lung, and heart at low doses. At high doses, albumin escape increased primarily in the liver, heart, and gastrointestinal tract but not the lung. The present study demonstrates that ET-1 increases hematocrit independent of splenic contraction or renal losses by enhancing loss of plasma volume to the interstitial space without affecting red blood cell volume. Because of the profound pressor effects of ET-1, it is likely that the plasma loss results from increased capillary hydrostatic pressure.
Hemodynamic performance and myosin light chain-1 expression of the hypertrophied left ventricle in aortic valve disease before and after valve replacement.
Authors: Sütsch G , Brunner U T , von Schulthess C , Hirzel H O , Hess O M , Turina M , Krayenbuehl H P , Schaub M C
Published: June 2012

Previously, we have reported on the selective accumulation of an atrial-like myosin light chain-1 (ALC1) in different forms of human ventricular hypertrophy. The present study involves the determination of ALC1 content in a control group and in patients with aortic stenosis or insufficiency before and 56 +/- 23 months after valve replacement and compares the hemodynamic and angiographic parameters. ALC1 was quantified densitometrically after two-dimensional electrophoretic resolution of biopsy specimens from the left ventricle and was expressed in percent of total ventricular light chain-1. The mean ALC1 content was 11.2 +/- 9.2% in preoperative aortic stenosis and 4.5 +/- 1.4% in aortic insufficiency, both being significantly (p less than 0.001) higher than the control value of 0.3 +/- 0.3%. After valve replacement, mean ALC1 content was lower than before, 4.2 +/- 3.3% (p less than 0.05) in stenosis and 3.4 +/- 3.1% (p = NS) in insufficiency. Left ventricular systolic pressure yields a significant (p less than 0.01) linear correlation (r = 0.45) with the ALC1 content in all preoperative and postoperative patients. Patient group averages of ALC1 content correlate directly with left ventricular systolic and end-diastolic pressure and wall thickness (r = 0.94-0.98) and, in an exponential fashion, with peak systolic circumferential wall stress (r = 0.98) but not with muscle mass or any other parameter. The ventricular ALC1 binds to myosin in proportion to its occurrence in the myocardium. The content of the endogenous ventricular light chain-1 did not change under pathological hemodynamics. The response in expression of the ALC1 to pressure and volume overload suggests an adaptational process.(ABSTRACT TRUNCATED AT 250 WORDS)
Activation of the cardiac ATP-sensitive K+ channel by ER-001533, a newly synthesized vasorelaxant.
Authors: Shen W K , Tung R T , Kurachi Y
Published: June 2012

Effects of ER-001533 (ER), a newly synthesized vasorelaxant, on the membrane currents were examined in single ventricular cells of guinea pigs. The patch-clamp technique was used in the "whole-cell" and "inside-out" patch configurations. In the whole-cell clamp condition, ER induced a time-independent K(+)-dominant current, which was inhibited by glibenclamide (1-3 microM), suggesting that ER activated the cardiac ATP-sensitive K+ channel (KATP). To elucidate the mechanism of ER-mediated KATP channel activation, the drug was applied to the inside-out patches before and after channel "run-down." Since nucleotide diphosphates could induce the channel openings after complete run-down, effects of the drug on the nucleotide diphosphate-induced channel openings were also examined. Before run-down, ER activated the KATP channel only in the presence of ATP. ER shifted the relation between [ATP]i and the channel activity to the right in a concentration-dependent fashion without a significant alteration of the slope. After channel run-down, ER did not affect the channel openings either in the absence or in the presence of UDP. However, ER could relieve the ATP-gamma-S inhibition of the UDP-induced channel openings. Thus, we conclude that ER antagonizes the inhibitory effect of ATP on the KATP channel in a competitive manner, thereby enhancing the channel openings.