bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of the heart to stimulation of aortic body chemoreceptors in dogs.
Authors: Karim F , Hainsworth R , Sofola O A , Wood L M
Published: June 2012

We stimulated the aortic chemoreceptors in dogs that were anesthetized with chloralose and artificially ventilated by perfusing the isolated aortic arch with venous blood. Inotropic responses were determined by measuring the maximum rate of change of left ventricular pressure (dP/dt max) with aortic pressure and heart rate held constant. Stimulation of the aortic chemoreceptors resulted in an average increase in heart rate of 14 +/- 2.0 beats/min (mean +/- SE) from 166 +/- 7.7 beats/min and an increase in dP/dt max of 501 +/- 85 mm Hg/sec from 3508 +/- 154 mm Hg/sec. These changes were statistically significant (P less than 0.001). The afferent pathway of the reflex was shown to be in the vagus nerves and the efferent pathway in the cardiac sympathetic nerves. In some of the dogs, the carotid chemoreceptors were also stimulated. This resulted in decreases in heart rate and dP/dt max of 48 +/- 24 beats/min and 795 +/- 142 mm Hg/sec. Thus we have shown that stimulation of aortic chemoreceptors evokes chronotropic and inotropic responses opposite to those evoked from stimulation of carotid chemoreceptors.
Suppression of myocardial protein degradation in the rat during fasting. Effects of insulin, glucose, and leucine.
Authors: Curfman G D , O'Hara D S , Hopkins B E , Smith T W
Published: June 2012

To study the effects of leucine, glucose, and insulin on myocardial protein degradation in fed and fasted nutritional states, we developed and validated a sensitive method for measuring rates of total protein degradation in rat isolated left atrial preparations. Fasting resulted in a progressive decrease in myocardial protein breakdown to 71% of control over a 24-hour period, with no further reduction in degradation rate between 24 and 72 hours of fasting. Insulin (100 mU/ml) suppressed atrial protein degradation by 38% in fed animals (P less than 0.001) and by 51% in fasted animals (P less than 0.001). Glucose alone had no effect on protein degradation in either nutritional state. At 5 times normal plasma levels, leucine suppressed protein breakdown by 21% in fed and by 15% in fasted animals. The decrease in degradation induced by fasting and the absence of an effect of glucose are in contrast to the behavior reported for skeletal muscle.
The effect of antiarrhythmic drugs on depressed conduction and unidirectional block in sheep Purkinje fibers.
Authors: Wald R W , Waxman M B , Downar E
Published: June 2012

We studied the effect of therapeutic concentrations of lidocaine, procainamide, quinidine, propranolol, and diphenylhydantoin on two models of depressed conduction and unidirectional block produced by asymmetric focal cooling and crushing in sheep Purkinje fibers. All drugs were shown to induce reversible deterioration of conduction. Unidirectional block was converted to bidirectional block with each drug. Improvement of conduction was rare and conversion of unidirectional block to bidirectional conduction never was observed. These experiments suggest that all five drugs may act by a uniform mechanism of action in some reentrant ventricular arrhythmias involving a zone of depressed conduction or unidirectional block within the Purkinje network.
The relative time course of early changes in mitochondrial function and intracellular pH during hypoxia in the isolated toad ventricle strip.
Authors: LaManna J C , Saive J J , Snow T R
Published: June 2012

Changes in the intracellular H+ ion concentration (pHi) and in the oxidation-reduction state of the respiratory chain were measured spectrophotometrically in the isolated ventricle strip from the toad (Bufo marinus). The relative time course of the delta pHi as indicated by changes in light absorption of the pH dye neutral red, cytochrome c, and peak isometric twitch tension were compared during transient hypoxic episodes. The first detectable change in pH occurred 4.5 minutes after the peak twitch tension began to decrease with the onset of hypoxia. The initial decrease in tension and reduction of cytochrome c occurred at a similar time prior to the change in pHi. On reoxygenation, cytochrome c rapidly became oxidized, and the pHi and tension recovered more slowly. During acidification by increasing superfusate PCO2, pHi and tension decreased together, and cytochrome c did not change significantly. Thus, although changes in pHi do affect mechanical performance, these results show that mechanical dysfunction pursuant to hypoxia is not directly attributable to intracellular acidification.
Nonlinearities of the human carotid baroreceptor-cardiac reflex.
Authors: Eckberg D L
Published: June 2012

Carotid baroreceptors of nine healthy young men and women were stretched or compressed with neck suction or pressure, before and after beta-adrenergic and cholinergic blockade, to evaluate several nonlinearities of sinus node baroreflex responses. Sinus node inhibition was related linearly to the intensity of brief baroreceptor stimuli over a range extending from carotid-distending pressures of about 101 +/- 5 (mean +/- SE) to 160 +/- 6 mm Hg (the subject's average systolic pressure was 108 +/- 2 mm Hg). Sinus node response to sustained (5 seconds) neck suction or pressure were strikingly asymmetrical. Responses were abolished by atropine, or by atropine and propranolol. Propranolol alone augmented sinus node responses to both neck suction and pressure. These results suggest that, in normal human subjects, sinus node responses to abrupt alterations of afferent baroreceptor traffic are nonlinear and are mediated by fluctuations of efferent cholinergic activity. Most of the observed nonlinear behavior of the integrated reflex can be explained on the basis of known properties of afferent and central portions of the baroreflex arc.
Automaticity and entrance block induced by focal depolarization of mammalian ventricular tissues.
Authors: Ferrier G R , Rosenthal J E
Published: June 2012

Isolated canine interventricular septa were studied with standard microelectrode techniques. Focal automaticity was induced by applying depolarizing current through an extracellular pipet in contact with the right bundle branch (RBB) of the ventricular specialized conducting system. Automaticity appeared with depolarization to transmembrane potentials of -50 mV or less. The spontaneous activity was neither depressed nor accelerated when overdrive suppression was attempted. Activity originating within the focus propagated into fully polarized surrounding tissue. However, entrance block, phasically related to the spontaneous cycle length, was an intrinsic property of these foci. Early premature beats initiated outside the focus failed to enter the focus, but the resulting electrotonus delayed the next automatic beat. Late premature beats captured and thereby accelerated the focus. Thus, the automatic foci could be extrafocal activity. Consequently, continous pacing at various rates precipitated complex rhythms with fixed coupling. Similar foci with exit conduction, entrance block, and electrotonic modulation also were demonstrated in focally depolarized papillary muscles in feline septal preparations. The unique properties of focally depolarized areas in which spontaneous activity is generated at low membrane potentials provide a mechanism capable of generating a wide array of arrhythmias.
Comparison of the distribution of intramyocardial pressure across the canine left ventricular wall in the beating heart during diastole and in the arrested heart. Evidence of epicardial muscle tone during diastole.
Authors: Stein P D , Sabbah H N , Marzilli M , Blick E F
Published: June 2012

Computations of compliance of the left ventricle (LV) during diastole assume passive tissue characteristics. To evaluate this assumption, we measured diastolic LV intramyocardial pressure simultaneously in the subepicardium and subendocardium in 18 open-chest dogs, using 1-mm in diameter micromanometers. Subepicardial pressure, 26 +/- 1 mm Hg (mean +/- SEM) exceeded subendocardial pressure, 14 +/- 1 mm Hg (P less than 0.001), and it exceeded left ventricular end-diastolic pressure (LVEDP) (9 +/- 1 mm Hg) (P less than 0.001). After an infusion of dextran-40 (10 dogs), subepicardial diastolic pressure increased to 42 +/- 4 mm Hg which was higher than diastolic subendocardial pressure, 26 +/- 2 mm Hg (P less than 0.001) and LVEDP, 24 +/- 2 mm Hg (P less than 0.001). Following cardiac arrest (12 dogs) with the intramyocardial probes unchanged in position, LV intracavitary pressure, 9 +/- 1 mm Hg, and subendocardial pressure, 13 +/- 3 mm Hg, did not differ significantly from the pressures in the beating heart. Subepicardial pressure, 9 +/- 1 mm Hg, was lower than in the beating heart (P less than 0.001). Following distention of the arrested LV (12 dogs), subepicardial pressure, 31 +/- 7 mm Hg, was lower than both subendocardial pressure, 58 +/- 12 mm Hg (P less than 0.001) and LV intracavitary pressure, 54 +/- 11 mm Hg (P less than 0.001). These observations indicate that tone is maintained by the subepicardium during diastole. Furthermore, the LV wall does not appear to behave as a passive shell during ventricular filling.
Morphometric study of early postnatal development of the thoracic aorta in the rat.
Authors: Olivetti G , Anversa P , Melissari M , Loud A V
Published: June 2012

Tissue, cellular, and subcellular morphometry of the thoracic aorta in 1-, 5- and 11-day-old rats was used to quantify the cellular hypertrophy and proliferation of smooth muscle cells and the absolute increases in volume of elastic laminase and collagen during the early postnatal period. In the 1- to 5-day interval, total wall volume increased 2.9-fold, wall thickness and the number of smooth muscle cells doubled, mean cell volume increased by 40%, and the volumes of elastic laminae and collagen increased 3.7- and 3.3-fold, respectively. From 5 to 11 days, circumferential growth of the aortic wall, without further thickening, produced smaller and unequal growth increments of each of its component structures, with increases in collagen (3.2-fold) > elastic laminae (2.3-fold) > muscle cells (1.6-fold). In the overall growth of smooth muscle cells (4.6-fold) from 1 to 11 days, only the cytoplasmic volume fractions of glycogen aggregates and rough endoplasmic reticulum were altered significantly (-76%, +32%). Certain aspects of normal postnatal aortic growth paralleled the response of adult aorta to experimentally induced hypertension.
Angiotensin II increases electrical coupling in mammalian ventricular myocardium.
Authors: Hermsmeyer K
Published: June 2012

Electrical measurements of current flow in ventricular myocardium immersed in silicone oil showed that angiotensin II increases the cell-to-cell spread of current within seconds. The increases in current spread and conduction velocity occur without any changes in resting membrane potential or maximum rate of rise of the action potential. The concentration range was 10 nM to 10 microM, with an ED50 of 100 nM for angiotensin exposures lasting about 10 seconds. The larges effects were an apparent decrease in resistance through the cellular pathway to 50% of control and a 40% increase in conduction velocity, which returned to control in about 15 minutes. Continuous or repeated exposure to angiotensin caused desensitization to appear. These effects were found with or without denervation by 6-hydroxydopamine and beta-adrenergic blockade by 1 microM propranolol in calf, pig, sheep, and rabbit ventricular myocardium. Therefore, angiotensin appears to increase electrical conduction rapidly and directly in cardiac muscle by decreasing resistance through the cellular pathway.
Atrioventricular conduction disturbances during hypoxia. Possible role of adenosine in rabbit and guinea pig heart.
Authors: Belardinelli L , Belloni F L , Rubio R , Berne R M
Published: June 2012

Adenosine and related compounds can produce atrioventricular (A-V) conduction block. Similar conduction disturbances are observed in myocardial hypoxia. To investigate the possibility that adenosine might be causally involved in hypoxic conduction disturbances, we measured A-V conduction times, subdivided into atrial-to-His bundle (A-H) and His bundle-to-ventricular (H-V) intervals, with extracellular electrodes in isolated rabbit and guinea pig hearts perfused with modified Krebs-Henseleit solution. Adenosine produced dose-dependent prolongation of A-V conduction time in both species, although guinea pig hearts responded to lower doses (10(-7) M) and showed a steeper dose-response relationship than rabbit hearts. Higher adenosine doses produced second-degree heart block in both species. Conduction delay was confined to the A-H interval, implicating action on A-V node cells. Further investigation of guinea pig hearts revealed a specific antagonism towards adenosine's effects by 10(-5) M aminophylline. Conduction disturbances produced by acetylcholine or MnCl2 were unaffected by aminophylline as were adenosine's effects by atropine. Perfusion with hypoxic perfusate caused A-V conduction delays and second-degree block in guinea pigs hearts. This effect was dramatically attenuated by aminophylline. We conclude that endogenously released adenosine may cause at least some of the A-V conduction disturbances associated with acute myocardial hypoxia. Furthermore, methylxanthines may prove to be of therapeutic value in combatting such disturbances in a clinical setting.
Effects of infarcted myocardium on regional blood flow measurements to ischemic regions in canine heart.
Authors: Murdock R H , Cobb F R
Published: June 2012

The present study assesses effects of acutely infarcted myocardium on apparent microsphere loss as a function of time, determines effects of apparent microsphere loss on blood flow measurements to ischemic regions, and determines to what extent apparent microsphere loss alters interpretation of serial measurements of collateral blood flow. Studies were performed in 35 awake mongrel dogs chronically instrumented with catheters in the aorta and left atrium and an occluder on the proximal circumflex coronary artery. Myocardial blood flow was measured before and 15 minutes after complete occlusion. Dogs were randomly divided into four groups to be killed at 6 and 24 hours, and 3 and 6 days. In the 3-day group, an additional blood flow measurement was made 24 hours postocclusion. The entire left ventricle was sectioned into 1- to 2-g samples and myocardial blood flow determined. The ratio of preocclusion blood flow in each ischemic sample to mean nonischemic flow was used to calculate apparent microsphere loss and to correct ischemic blood flow in each sample. Significant apparent microsphere loss occurred in epicardial layers at 24 hours and in epi- and endocardial layers at 3 and 6 days; maximum loss at each interval was 22.3, 19.4, and 22.2% respectively. Absolute blood flow corrections for ischemic myocardium were small, range -0.035 to 0.083 ml/min per g. Changes in flow to ischemic regions between 15 minutes and 24 hours were comparable before and after correction for apparent microsphere loss. Although infarction resulted in significant apparent microsphere loss, effects on ischemic blood flow measurements were very small and consequently did not prevent interpretation of serial blood flow measurements after infarction in animals killed at 3 days.
An analysis of the mechanical disadvantage of myocardial infarction in the canine left ventricle.
Authors: Bogen D K , Rabinowitz S A , Needleman A , McMahon T A , Abelmann W H
Published: June 2012

An isotropic, initially spherical, membrane model of the infarcted ventricle satisfactorily predicts ventricular function in the infarcted heart when compared to clinical information and available ventricular models of higher complexity. Computations based on finite element solutions of this membrane model yield end-diastolic and end-systolic pressure-volume curves, from which ventricular function curves are calculated, for infarcts of varying size and material properties. These computations indicate a progressive degradation of cardiac performance with increasing infarct sizes such that normal cardiac outputs can be maintained with Frank-Starling compensation and increased heart rate for acute infarcts no larger than 41% of the ventricular surface. The relationship between infarct stiffness and cardiac function is found to be complex and dependent on both infarct size and end-diastolic pressure, although moderately stiff subacute infarcts are associated with better function than extensible acute infarcts. Also, calculations of extensions and stresses suggest considerable disruption of the border zone contraction pattern, as well as elevated border zone systolic stresses.
Developmental changes in the sensitivity of the chick embryo ventricle to beta-adrenergic agonist during adrenergic innervation.
Authors: Higgins D , Pappano A J
Published: June 2012

As early as the 4th embryonic day, the ventricle of the chick embryo responded to isoproterenol (Iso) with an increase in the force of contraction; at all ages studied, this positive inotropic effect was accompanied by an increased rate of tension development. There was a transient, 10-fold decrease in the sensitivity (increase in ED50) of the right ventricle to Iso between the 16th and 21st embryonic day. This change in the sensitivity to Iso was not due either to an increased inactivation of Iso by non-neuronal cells or to a change in the thickness of the ventricle. It was found that adrenergic nerves were first capable of altering ventricular contractility on the 16th embryonic day. Whereas they interfered with the function of adrenergic nerves, injections of reserpine or 6-hydroxydopamine had no effect on the subsensitivity to Iso. Furthermore, these agents did not affect the normal developmental changes in heart weight. We conclude that the local release of transmitter from adrenergic nerves does not cause the transient subsensitivity of the ventricle of the chick embryo to beta-adrenergic agonists.
Partition of carotid sinus baroreceptor response in dogs with chronic renal hypertension.
Authors: Koushanpour E , Kenfield K J
Published: June 2012

This study was designed to determine whether resetting of the carotid sinus baroreceptors in chronic renal hypertension is due to altered distensibility of the wall, or changes in the properties of the receptor elements, or both. Dogs were made hypertensive by 50% constriction of the left renal artery with a Goldblatt clamp and by right nephrectomy one week later. Five to nine weeks after nephrectomy, when mean blood pressure had risen by 35-46 mm Hg, the isolated carotid sinus wall deformation, measured from still photographs, and gross baroreceptor nerve action potentials (N) were recorded in response to step intrasinus pressure forcings (P), ranging from zero to 300 mm Hg, in increments of 25 mm Hg. Measured wall deformation was converted to strain-energy density (SED), a scalar value, as the best indicator of the mechanical state of the sinus wall. Plots of N vs. P data followed an S-shaped pattern, but were shifted toward the P-axis, as compared to controls. Plots of SED vs. P, though linear over most of the pressure range, were shifted toward the SED-axis, as compared to controls. A plot of N vs. SED, derived from the composite plots of N vs. P and SED vs. P, followed an S-shaped pattern and also was shifted toward the SED-axis. We conclude that the nonlinearity in the N vs. P curve is due largely to the inability of the receptor elements to respond to increasing wall strain and to resetting of the baroreceptors due to changes in the receptor properties rather than in the wall elements.
Cholesterol potentiates the coronary artery response to norepinephrine in anesthetized and conscious dogs.
Authors: Rosendorff C , Hoffman J I , Verrier E D , Rouleau J , Boerboom L E
Published: June 2012

We investigated the effect of hypercholesterolemia on coronary and cardiac hemodynamic responses to intracoronary norepinephrine (NE) (0.01 to 10.0 micrograms/min as the bitartrate) in a Gregg cannula autoperfusion system. Coronary blood flow was measured by the radioactive microsphere technique in two groups of open-chest dogs anesthetized with pentobarbital: 10 controls and 8 that were fed a cholesterol-rich diet (CD) which doubled the serum cholesterol level. In the control dogs, NE in doses of 0.01 to 1.0 micrograms/min had no effect on coronary vascular resistance (CVR) but 10 micrograms/min caused a significant decrease to 0.58 +/- 0.12 of control. In the CD dogs, NE at doses of 1.0 and 10.0 micrograms/min significantly reduced CVR, to 0.72 +/- 0.06 and 0.52 +/- 0.11 of control, respectively. There was no consistent effect of NE, at these doses, on myocardial oxygen uptake, left ventricular stroke work index, or maximal positive dP/dt. In a second series of experiments we measured coronary flow with electromagnetic flowmeters in 11 chronically instrumented conscious dogs, 5 controls, and 6 CD. In the control dogs, intravenously administered NE hydrochloride, 0.01 microgram/min, reduced CVR to 0.74 +/- 0.07 of control, and 1.0 microgram/min increased CVR to 1.26 +/- 0.09 of control. In the CD animals, these effects were seen at a 10-fold lower NE dose, 0.001 microgram/min (0.83 +/- 0.11 of control) and 0.1 microgram/min (1.32 +/- 0.06 of control). The vasodilation was blocked by propranolol, and vasoconstriction by phentolamine. We conclude that NE at low doses activates beta-adrenoreceptors to reduce CVR and at higher doses activates alpha-adrenoreceptors to increase CVR; the vasoconstrictor response is inhibited in pentobarbital anesthetized dogs, and hypercholesterolemia sensitizes coronary vessels to both the dilator and constrictor effects of NE.
Coarctation of the aorta and baroreceptor resetting. A study of carotid baroreceptor stimulus-response characteristics before and after surgical repair in the dog.
Authors: Igler F O , Boerboom L E , Werner P H , Donegan J H , Zuperku E J , Bonchek L I , Kampine J P
Published: June 2012

We studied baroreceptor function in dogs before and after surgical repair of coarctation of the aorta by direct recording of multifiber carotid sinus (CS) nerve activity (NA) during alteration of pulsatile arterial pressure with systemic phenylephrine and nitroprusside, and during static pressure changes using a CS pouch preparation. Coarctation was induced by banding the proximal thoracic aorta in ten 3- to 5-day old puppies. One and one-half years later, five of these coarctated animals were studied before, and five were studied 3-7 months after, surgical repair. Five adult animals also were studied 4-6 months after the proximal thoracic aorta had been banded. Controls were eight normal adult dogs. Threshold pressure at which NA began, saturation pressure at which NA reached a maximum, and slope (% Max NA/mm Hg) of the linear portion of the stimulus-response curve were determined. Pulsatile manipulations of pressure elicited normal sensitivity (slope) in dogs with coarctation but static nonpulsatile pressure changes showed depressed sensitivity compared to controls. After surgical repair, threshold and saturation returned toward normal; sensitivity determined with static pressure manipulations returned to control value. Coarctation reset CS baroreceptors to operate at higher pressures in both puppies and adult dogs and repair of coarctation returned function toward normal. We conclude that resolution of hypertension after repair of coarctation may depend upon baroreceptor readaptation.
The effect of hemorrhagic hypotension on urinary kallikrein excretion, renin activity, and renal cortical blood flow in the pig.
Authors: Maier M , Starlinger M , Wagner M , Meyer D , Binder B R
Published: June 2012

We measured urinary kallikrein by its esterolytic and kinin-forming activity in 5-minute urine samples obtained throughout continuous bleeding experiments in pigs to correlate possible changes in urinary kallikrein excretion during hemorrhagic hypotension with resin activity and renal cortical blood flow. Renin activity was determined in venous blood samples and renal cortical blood flow was estimated by the radiolabeled microsphere technique. The rate of urinary kallikrein excretion was increased about 4-fold within an arterial pressure range of 100-70 mm Hg, whereas below 70 mm Hg, arterial pressure urinary kallikrein activity declined to undetectable values. Renin activity was increased only 2-fold in the arterial pressure range between 100 and 70 mm Hg but was increased 4-fold at pressures below 70 mm Hg. The pressure range of 100 to 70 mm Hg corresponded to the autoregulation of renal cortical blood flow and glomerular filtration rate; below that pressure range, renal cortical blood flow dropped to about 10% of the initial value. Therefore, it seems that urinary kallikrein is activated mainly during the period of autoregulation, whereas renin activity is, in the main, increased below the autoregulatory range of pressure. The vasodilatory urinary kallikrein kinin system might be involved in maintaining sufficient local blood flow during autoregulation whereas a decrease in blood pressure below the autoregulatory range leads to a major increase in renin activity, thus illustrating the attempt of the organism to reestablish sufficient blood pressure to maintain autoregulation.
Pulmonary vasodilator responses to catecholamines and sympathetic nerve stimulation in the cat. Evidence that vascular beta-2 adrenoreceptors are innervated.
Authors: Hyman A L , Nandiwada P , Knight D S , Kadowitz P J
Published: June 2012

We investigated the effects of catecholamines and sympathetic nerve stimulation in the feline pulmonary vascular bed under conditions of controlled pulmonary blood flow. Norepinephrine and nerve stimulation caused dose- and stimulus frequency-dependent increases in pulmonary vascular resistance. However, when pulmonary vascular tone was enhanced and alpha receptors blocked, norepinephrine and nerve stimulation caused dose- and frequency-dependent decreases in pulmonary vascular resistance. The decreases in pulmonary vascular resistance were blocked with propranolol and were of greater magnitude than were constrictor responses observed under basal conditions. Vasodilator responses to nerve stimulation were not modified by atropine. Epinephrine and isoproterenol had marked vasodilator activity in the pulmonary vascular bed when pulmonary vascular tone was elevated. When alpha receptors were blocked, isoproterenol and epinephrine had similar vasodilator activity, and when beta receptors were blocked, epinephrine and norepinephrine had marked vasoconstrictor activity. Selective beta-1 receptors antagonists had little effect on vasodilator responses to isoproterenol, whereas responses to this substance were blocked by propranolol. These results suggest that presence of alpha-and beta-2 adrenoreceptors in the feline pulmonary vascular bed and that both types of adrenergic receptors are innervated by the sympathetic nervous system.
Reflex alpha-adrenergic coronary vasoconstriction during hindlimb static exercise in dogs.
Authors: Aung-Din R , Mitchell J H , Longhurst J C
Published: June 2012

We studied 18 alpha-chloralose-anesthetized dogs to determine if alpha-adrenergic coronary vasoconstriction occurs with hindlimb static exercise. Exercise was elicited by spinal cord ventral nerve root stimulation. Regional coronary blood flow was determined by the radioactive microsphere method. Animals were studied under four experimental conditions: control rest and static exercise, rest and static exercise after beta-adrenergic blockade with propranolol (2 mg/kg), rest and exercise after alpha-adrenergic blockade with phentolamine (.35 mg/kg), and rest and exercise after combined alpha- and beta-adrenergic blockade. Myocardial oxygen consumption during exercise was determined during control and during alpha-adrenergic blockade conditions. Control hindlimb static exercise resulted in significant increases in systolic (10.6%) and diastolic (12.5%) arterial pressures, heart rate (12.2%), and double product (24.6%). Associated with the increased demand for oxygen, myocardial oxygen consumption increased (33.6%) as did left ventricular myocardial flow (29.6%). However, left ventricular coronary vascular resistance was unchanged during static exercise. After beta-adrenergic blockade, systolic (12.2%) and diastolic (11.6%) arterial pressures and double product (10.7%) still increased significantly, but heart rate did not change with static exercise. In contrast, alpha-adrenergic vasoconstriction was unmasked as left (LV) and right (RV) ventricular myocardial blood flow decreased (LV: -30.0%, RV: -25.0%) and coronary vascular resistance increased (LV: 52.5%, RV: 45.3%) with static exercise. Combined alpha- and beta-adrenergic blockade abolished the reduction in myocardial blood flow and the increase in coronary vascular resistance which occurred with static exercise after beta-adrenergic blockade. These data suggest that, during static exercise, reflexes from skeletal muscles can cause alpha-adrenergic coronary artery vasoconstriction.
Development of dyadic junctional complexes between sarcoplasmic reticulum and plasmalemma in rabbit left ventricular myocardial cells. Morphometric analysis.
Authors: Page E , Buecker J L
Published: June 2012

Dyadic junctional couplings between cardiac sarcoplasmic reticulum (SR) and plasma membrane presumably are implicated in release of Ca2+ from terminal cisterns of SR during excitation-contraction coupling. We measured the areas of SR and plasma membrane involved in such couplings in late embryonic and neonatal rabbit left ventricles during a developmental period characterized by rapid cell growth and rapid accumulation of myofibrils. By morphometric methods previously applied to adult hearts, it could be shown that from the inception of the nascent T-system the surface density of dyadic couplings at T-tubular plasmalemma exceeds by about four-fold that at the external plasmalemmal envelope. Before the development of a T-system (similar to or approximately 10 days after birth) surface density of dyads, as well as total dyad areas per unit cell volume and per unit myofibrillar volume, increase progressively during embryonic life until they approach constancy at near adult values one day after birth. Constancy of total dyadic membrane area per unit myofibrillar volume during neonatal cell growth confirms that the membrane area of the activating system and the volume of myofibrils to be activated accumulate in a constant proportion.
Effects of exercise on the coronary and collateral vasculature of beagles with and without coronary occlusion.
Authors: Scheel K W , Ingram L A , Wilson J L
Published: June 2012

The purpose of this study was to determine if exercise stimulates coronary collateral vessel growth and if exercise after coronary occlusion can promote additional collateral growth. One group of 10 beagles served as control. The second group considered of 10 normal beagles exercised at 50% of maximum O2 consumption 7 days/week for 6 weeks. In the third group, the circumflex was occluded (Ameroid method) in eight beagles for 5 months. In the fourth group, seven beagles were exercised for 8 weeks following 3 months of circumflex occlusion. The coronary and collateral circulation was assessed, using an isolated heart preparation. It was found that exercise did not stimulate collateral growth in normal beagles. However, exercise after coronary occlusion doubled collateral conductance to be impaired vascular bed compared to animals with only coronary occlusions. Our study shows that, in beagles with coronary occlusion, exercise after a 3-month convalescent period promotes epicardial and intramyocardial (septa) collateral growth. Coronary reserve in the trained animals returned to 52% of initial capacity vs. 34% for the untrained animals.
Postnatal development of the M-band in rat cardiac myofibrils.
Authors: Anversa P , Olivetti G , Bracchi P G , Loud A V
Published: June 2012

Cardiac muscle fibers in rats at 1 and 5 days after birth showed little evidence of M-bands. An ultrastructural analysis of myofibrils failed to demonstrate dense M-band material in longitudinal sections or M-bridges in transverse sections of sarcomeres. M-bands began to increase in number after 5 days of postnatal life and were present in 60% of all sarcomeres at 11 days of age. Polypeptides with molecular weights of 190,000 (Ma) and 175,000 (Mb) were obtained by polyacrylamide-sodium dodecyl sulfate (SDS) gel electrophoresis of myofibril preparations. These two proteins were found in both 1- and 11-day-old rats and were considered to be specific components of the M-band. The densitometric analysis demonstrated that Ma and mb polypeptides increased approximately 2-fold during the interval from 1 to 11 days after birth. These structural and biochemical changes of the M-band material in myocytes appear to be related to the maturation of contractile function in the young heart.
The electrophysiological properties of normal neonatal and adult canine cardiac Purkinje fibers.
Authors: Reder R F , Miura D S , Danilo P , Rosen M R
Published: June 2012

To determine the basis for age-related changes that occur in the transmembrane action potentials (AP) of canine cardiac Purkinje fibers (PF), we used standard microelectrode techniques to study PF from normal neonatal and adult beagles. As previously shown, neonatal PF AP have a less negative maximum diastolic potential (MDP), a lower AP amplitude (amp) and maximum upstroke velocity of phase 0 (Vmax), and shorter AP duration measured at 50% and 100% repolarization than have those of adults. Further, the termination of phase 1 and the peak of phase 2 occur at more positive levels of membrane potential in neonatal PF. The less negative MDP in neonatal PF is associated with a lower intracellular potassium activity (aKi) as demonstrated with a K+-sensitive microelectrode. Neonatal PF showed greater depression of AP amp and Vmax during superfusion with the rapid Na+ channel blocker, tetrodotoxin (TTX), than did adult PF. The attainment of more negative voltages at the termination of phase 1 in adult compared to neonatal PF was not attributable to age-related differences in response to changes in drive cycle length, temperature, or external Cl- concentration. However, 4-aminopyridine, a blocker of the early, repolarizing potassium current, altered this variable in adult and not in neonatal PF. The effects of verapamil and AHR-2666, both slow inward current blockers; of TTX, which blocks a background inward Na+ current; and of TEA+, which blocks repolarizing K+ current, were studied on AP repolarization. Adult PF AP were more sensitive to the effects of AHR-2666, verapamil, and TEA+ and less sensitive to the effects of TTX than neonates.
Operational sensitivity and acute resetting of aortic baroreceptors in dogs.
Authors: Coleridge H M , Coleridge J C , Kaufman M P , Dangel A
Published: June 2012

Stimulus-response curves of aortic baroreceptors constructed by alternately increasing and decreasing pressure from a normal baseline or set-point differ from curves constructed by varying pressure in one direction only from an abnormally high or low pressure. In anesthetized dogs we recorded impulses from aortic baroreceptors with myelinated fibers, using a pressurized reservoir to control mean aortic blood pressure (MABP). After setting MABP to a baseline of 100 mm Hg (normal MABP in unanesthetized dogs), we constructed baroreceptor response curves by alternately decreasing MABP from 100 to 30 mm Hg, and increasing it from 100 to 180 mm Hg, in each case returning MABP to the baseline to obtain hysteresis loops. All baroreceptors were active at 100 mm Hg, their discharge averaging 15-16 impulses/sec. At all pressures above threshold, baroreceptors fired more when pressure was increasing than when pressure was decreasing. This hysteresis caused the steepest part of the response curve constructed in this manner to span the baseline value, demonstrating that, contrary to previous views, aortic baroreceptors signal decreases in pressure below the normal level, as well as increases above it. We also constructed response curves after holding MABP at a "hypertensive" baseline of 125 mm Hg for 20 minutes. "Hypertensive" curves demonstrated reversible resetting, shifting significantly to the right of "normotensive" curves so that baroreceptor threshold increased on average by 7 mm Hg (P less than 0.01). Both hysteresis and short-term resetting probably result from the viscoelastic behavior of wall elements with which baroreceptors are coupled.
Influence of secobarbital and alpha-chloralose, and of vagal and sympathetic interruption, on left ventricular activation after acute coronary artery occlusion in the dog.
Authors: Ruffy R , Lovelace D E , Knoebel S B , Zipes D P
Published: June 2012

The purpose of this study was to examine the effect of secobarbital vs. alpha-chloralose anesthesia, and of tonic autonomic influence, upon ischemia-induced subepicardial and subendocardial bipolar electrogram changes during acute coronary artery occlusion in the open-chest dog. We found that the degree of bipolar electrogram alterations for similar reductions of regional myocardial blood flow was less in dogs anesthetized with alpha-chloralose than in those anesthetized with secobarbital. We also noted greater electrogram change when the sympathetic system was unopposed by the vagus nerves. Finally, this study demonstrates the reproducibility of ischemia-induced changes in bipolar electrograms during serial, short term, acute coronary artery occlusions.
Variable effect of nifedipine on myocardial blood flow at three grades of coronary occlusion in the dog.
Authors: Weintraub W S , Hattori S , Agarwal J , Bodenheimer M M , Banka V S , Helfant R H
Published: June 2012

The effect of nifedipine on myocardial blood flow at various grades of coronary stenosis is unknown, Thus 22 open-chest dogs underwent carotid to left anterior descending perfusion with flow and perfusion pressure monitoring. Grades of coronary occlusion were defined by minimum diastolic perfusion pressure. six dogs (group 1) underwent moderate occlusion to 50 to 55 mm Hg diastolic perfusion pressure; (group 2), severe occlusion to 40 mm Hg perfusion pressure; and six (group 3), more severe occlusion at 25 mm Hg. Regional myocardial blood flow was measured with radioactive microspheres before and after the intracoronary injection of 10 microgram of nifedipine. In group 1, nifedipine induced epicardial hyperemia and little change in endocardial flow in the ischemic zone. In group 2, nifedipine induced epicardial hyperemia from 1.06 to 1.39 mg/g per min, but endocardial flow decreased from 0.70 to 0.60 ml/g per min. In group 3, there was no change in blood flow. Thus the effect of nifedipine on myocardial blood flow depends on the extent of occlusion. Furthermore for certain degrees of occlusion, redistribution of blood flow from endocardium to epicardium has been shown to occur.
Changes in cellular Na+, K+, and Ca2+ contents, monovalent cation transport rate, and contractile state during washout of cardiac glycosides from cultured chick heart cells.
Authors: Barry W H , Biedert S , Miura D S , Smith T W
Published: June 2012

To delineate more clearly the importance of altered monovalent cation transport rate in the mediation of the positive inotropic effects of cardiac glycosides, we studied changes in the contractile state and rate of uptake of K+ and Rb+ by monolayer cultures of chick embryo ventricular cells during exposure to and washout of ouabain and dihydro-ouabain. These cardiac glycosides produced a positive inotropic effect in this system, accompanied by a significant reduction in monovalent cation transport rate, by increases in cellular contents of Na+ and Ca2+, and by a decrease in cellular content of K+ as judged by radioisotopic tracer studies. Following removal of glycosides from media bathing the cultures, monovalent cation transport rate returned to normal within 1 minute, followed by a loss of inotropy which was complete by 7 minutes, a time at which cellular [Ca2+] had returned to normal. The bulk cellular concentration of Na+ remained increased, however, and that of K+ depressed for longer periods. Veratrine (1 microgram/ml) induced a positive inotropic effect, but caused a less marked increase in cellular [Na+] than did equipotent concentrations of ouabain and dihydroouabain. These results indicate that there is not a simple relationship between bulk cellular [Na+] and magnitude of inotropic effect in these cells, and are consistent with the proposal that there is a subsarcolemmal space in which [Na+] regulates Ca2+ fluxes and contractility, and in which [Na+] is regulated primarily by the balance between transsarcolemmal influx and Na+ pump rate and, to a lesser degree, by bulk [Na+].
Redundancy reduction for improved display and analysis of body surface potential maps. I. Spatial compression.
Authors: Lux R L , Evans A K , Burgess M J , Wyatt R F , Abildskov J A
Published: June 2012

The Karhunen-Loeve technique of random process representation was investigated as a method of quantitatively characterizing body surface potential maps. One hundred ninety-two lead body surface potential maps from 124 normal subjects and 97 patients with independently documented heart disease were used in the study. Each map frame in QRS and ST-T of 34 maps in a test set was represented as a linear sum of orthonormal distributions derived from the covariance matrix estimated from all QRS frames in the 221 training maps. A 16:1 reduction in spatial data of the test set was achieved with rms errors of 45 and 21 microV in QRS and ST-T, respectively. Results suggest that 12 independent waveforms, derived from the 192 measured ECGs, may be used in place of those 192 ECGs. In addition to providing a convenient and familiar method of display for map data, the technique puts the data in an appropriate form for quantitative statistical analysis.
Redundancy reduction for improved display and analysis of body surface potential maps. II. Temporal compression.
Authors: Evans A K , Lux R L , Burgess M J , Wyatt R F , Abildskov J A
Published: June 2012

This paper describes use of the Karhunen-Loeve expansion to identify and reduce temporal redundancy in electrocardiographic body surface potential maps (192 body surface leads recorded simultaneously at 1 kHz/channel for approximately 600 msec). Temporal data compression of about 20 to 1 was obtained with accurate representation of the original data. Use of separate sets of orthonormal basis functions for QRS and ST-T provided a more accurate representation than the basis derived from QRST. Combined with the spatial compression described in the preceding paper, overall map data compression of about 320 to 1 was obtained without significant loss of accuracy of representation or map appearance. With both spatial and temporal compression the 100,000 numbers which typically comprise a single cardiac complex were accurately represented by 216 coefficients. Using basis functions derived from a single cardiac complex were accurately represented by 216 coefficients. Using basis functions derived from a training set of 221 maps, the estimated average rms error of representation was 60 microV during the ST-T. For 34 test maps which were not part of the training set, measured average errors were 64 microV during the QRS and 23 microV during the ST-T. This technique provides a basis for quantification of the diagnostic content of maps and automated classification of maps.
Effects of myocardial ischemia on quantitative ultrasonic backscatter and identification of responsible determinants.
Authors: Mimbs J W , Bauwens D , Cohen R D , O'Donnell M , Miller J G , Sobel B E
Published: June 2012

Quantitative characterization of myocardial properties represent a rapidly emerging area of echocardiographic investigation. Because measurement of the ultrasonic integrated backscatter is theoretically applicable to analysis in vivo with reflected ultrasound, this study was performed to develop and evaluate a suitable method for measurement of quantitative backscatter in vivo. In view of the desirability of characterizing ischemic myocardium noninvasively, the study was performed with animal preparations simulating myocardial ischemia in humans. In one series of open-chest dogs, integrated backscatter among 22 ischemic regions was increased by 200% (P less than 0.01) compared to values in control regions within 1 hour after coronary occlusion and by 400% (-45.1 +/- 0.7 dB compared to -50.9 +/- 0.4 dB) (P less than 0.001) within 6 hours. In a second series of open-chest dogs, ischemia was quantified with 141Ce microspheres, and mean integrated backscatter was found to increase (280% of control) (P less than 0.01) in regions with flow less than 20% of control 2 hours following coronary occlusion. Additional studies with perfused hearts revealed two determinants of the increased ultrasonic backscatter observed: (1) an increase in cardiac fluid content reflected by the wet-to-dry weight ratio, and (2) the contributions of formed elements in whole blood. The results indicate that ultrasonic integrated backscatter distinguishes severely ischemic from nonischemic myocardium in vivo in open-chest animals. Because it was possible to obtain these results in the reflection mode, potential extension of the approach to clinical applications is promising.
Interactions among inflammatory mediators on edema formation in the canine forelimb.
Authors: Amelang E , Prasad C M , Raymond R M , Grega G J
Published: June 2012

Prostaglandin E1, 4 microgram/min, infused locally intra-arterially (ia) for 60 minutes into forelimbs perfused at constant pump controlled inflow produced decreases in perfusion pressure, increases in lymph total protein concentration (approximately equal to g/100 ml), and small increases in weight (23 g) owing to edema formation. Histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, infused locally ia for 60 minutes produced large increases in lymph flow, lymph total protein concentration, total protein transport, and weight (70 g and 130 g, respectively). However, the local ia infusion of prostaglandin E1, 4 microgram/min, together with histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, produced weight increases of 180 g and 236 g, respectively, and the rate of weight gain during the combination infusions greatly exceeded that produced by infusions of histamine or bradykinin alone. Moreover, the increases in lymph flow and in total protein transport far exceeded those produced by infusions of prostaglandin E1 and histamine or bradykinin alone or additively. The edema produced by the local ia infusion of prostaglandin E1, 4 microgram/min, together with bradykinin, 10 microgram base/min, was even more more marked in naturally perfused forelimbs. Similarly, the local ia infusion of histamine, 4 microgram base/min, or bradykinin, 0.8 microgram base/min, for 60 minutes into forelimbs perfused at constant inflow produced increases in lymph flow, lymph total protein concentration, total protein transport, and weight (38 g and 14 g, respectively). In contrast, histamine, 4 microgram base/min, and bradykinin, 0.8 microgram base/min, infused together locally ia for 60 minutes produced increases in weight of 118 g. The increase in lymph flow and total protein transport was considerably more marked during the combined infusions than during the infusions of histamine or bradykinin alone or additively.