bluuebunny/crossref_metadata_2025 huggingface dataset:
Participation of Central Noradrenergic Neurons in Arterial Baroreceptor Reflexes in the Rabbit: A STUDY WITH INTRACISTERNALLY ADMINISTERED 6-HYDROXYDOPAMINE
Authors: CHALMERS J. P. , Reid J. L.
Published: June 2012

Rabbits were given intracisternal injections of 6-hydroxydopamine (6-OH-DA) that caused selective ablation of central noradrenergic neurons without damaging peripheral sympathetic nerves. Administration of 6-OH-DA (600 µg/kg, intracisternally) to normal rabbits produced a permanent bradycardia of about 30%, which was initiated centrally and mediated mainly through the vagus, and caused a brief reduction in mean arterial blood pressure, which was due to transient withdrawal of alpha-sympathetic tone. Treatment with 6-OH-DA (600 µg/kg) completely prevented the increases in arterial blood pressure seen on the seventh and the fourteenth day after sinoaortic denervation in control rabbits, although there was a transient increase in blood pressure for 1 day after denervation in the group treated with 6-OH-DA. Central norepinephrine concentrations were reduced in all areas, especially in the spinal cord (to less than 10% of control), in the denervated rabbits treated with 6-OH-DA compared with the levels in denervated controls. When 6-OH-DA (600 µg/kg, intracisternally) was given to rabbits with neurogenic hypertension produced by buffer nerve section, it caused an immediate and persistent return of pressure to the level that existed before denervation. Probably, the integrity of central noradrenergic neurons is necessary for the development of sustained increases in arterial blood pressure following sinoaortic denervation. We suggest that central noradrenergic nerves form an essential link in the baroreceptor reflex arc, possibly at the bulbospinal level.
Renin in Rats with Spontaneous Hypertension
Authors: SEN SUBHA , SMEBY ROBERT R. , BUMPUS F. Merlin
Published: June 2012

An age-dependent study of plasma renin activity (PRA), kidney renin activity (KRA), and plasma renin substrate was carried out in rats with spontaneous hypertension during the prehypertensive, the early hypertensive, and the established hypertensive phases of their disease. PRA and KRA were both significantly elevated before and during the initial phase of hypertension and normal or subnormal during the established phase. In normal controls, neither KRA nor PRA was significantly different during the entire growth period. Plasma renin substrate was elevated throughout the growth period in rats with hypertension. This relationship between renin and blood pressure suggests that renin may play a primary role, possibly along with other factors, in the initiation of hypertension in rats with spontaneous hypertension.
Effect of Insulin on the Performance and Metabolism of the Anoxic Isolated Perfused Rat Heart
Authors: WEISSLER ARNOLD M. , ALTSCHULD RUTH A. , GIBB LORRAINE E. , POLLACK MARY ELLEN , KRUGER FRED A.
Published: June 2012

When the oxygen supply to the myocardium is compromised, glycolysis may provide the critical energy necessary for the heart's survival. We investigated whether insulin, through its effects on myocardial glycolysis, influences the performance and the metabolism of the perfused rat heart during anoxia. Hearts in a modified Langendorff apparatus were perfused for 30 minutes with anoxic media containing glucose (50-500 mg/100 ml) with and without insulin (100 munits/ml) or with anoxic media containing 200 mg glucose/100 ml and varying insulin concentrations (0.1-100 munits/ml). Hearts were paced, and left ventricular pressure, maximum rate of rise of left ventricular pressure, and lactate production were monitored. Increasing glucose concentration alone progressively enhanced performance and lactate generation in the beating anoxic heart. Addition of insulin resulted in significant increases in left ventricular performance and lactate production at all levels of glucose concentration. The myocardial content of high energy intermediates (creatine phosphate, adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate) after 30 minutes of anoxia was not altered by varying concentrations of glucose or insulin. To assess the effects of insulin and glucose in the absence of contraction, hearts were arrested with media containing a high potassium concentration (26 mEq/liter). Although lactate production was lower in arrested hearts than it was in beating hearts, it was enhanced by insulin. Insulin also produced significant increases in high-energy intermediates in arrested hearts. It was concluded that insulin increases the utilization of glucose and thus causes the enhancement of ventricular performance in the anoxic heart.
Pressure and Flow Generated by the Left Ventricle against Different Impedances
Authors: ELZINGA GIJS , WESTERHOF NICOLAAS
Published: June 2012

To study selective changes in capacitive and resistive load under constant left atrial filling pressure, isolated cat hearts were loaded with a hydraulic model simulating the input impedance of the systemic arteries. The model was constructed so that resistive (peripheral resistance) and capacitive (total arterial compliance) characteristics could be changed independently. Aortic and left ventricular pressure and aortic flow, as generated by the left ventricle against the different impedances, were measured. An increase in resistance resulted in an increase in systolic, diastolic, and mean aortic pressure. A decrease in capacitance caused a small increase in systolic pressure and a decrease in diastolic and mean aortic pressure. Mean left ventricular pressure increased when resistance increased or capacitance decreased. Both peak flow and mean flow decreased when resistance increased or capacitance decreased. We attempted to explain these observations by the concept of source impedance. This concept had been, until now, incorrectly approached, because the nonlinearity arising from the aortic valves had been neglected. The correct computations met with difficulties, but it was shown that the isolated heart, with constant atrial filling pressure, behaved as neither a flow source nor a pressure source.
Evidence for Direct Control of Coronary Vascular Tone by Oxygen
Authors: GELLAI MIKLOS , NORTON JAMES M. , DETAR REED
Published: June 2012

The interaction between the effects of oxygen and adenosine on acetylcholine-induced contractile tension was observed in helical coronary arterial strips suspended in physiological salt solution. It was found that (1) steady-state contractile tension was unaffected or depressed 5-20% when oxygen pressure (Po
2
) was diminished to levels as low as 5-10 mm Hg, (2) contractile tension was markedly depressed at a Po
2
of 0 mm Hg, (3) adenosine-induced relaxation of contractile tension was inversely proportional to Po
2
in the tissue bath, and (4) in the presence of adenosine at a concentration just adequate to inhibit contractile tension at a Po
2
of 10 mm Hg, contractile tension was directly proportional to bath Po
2
. The latter two observations were usually most apparent at a Po
2
between 10 and 40 mm Hg. It is proposed that the vasodilating effect of adenosine on the intact coronary vasculature may be most effective during myocardial hypoxia and that physiological control of coronary vascular tone may be more closely related to variations in local Po
2
than to variations in local concentrations of adenosine.
Effect of Chronic Myocardial Ischemia on the Activity of Carnitine Palmitylcoenzyme A Transferase of Isolated Canine Heart Mitochondria
Authors: WOOD JEANIE MCMILLIN , SORDAHL LOUIS A. , LEWIS ROBERT M. , SCHWARTZ ARNOLD
Published: June 2012

The effect of chronic ischemia on the activity of carnitine palmitylcoenzyme A transferase (PCoAT) was examined. Control mitochondria were isolated from the left ventricle of normal hearts and from the uninvolved areas of ischemic hearts. Mitochondria from ischemic tissue were isolated from the left ventricle of chronically ischemic hearts. Formation of the enzyme product, palmityl-
14
C-carnitine, was markedly depressed in control mitochondria isolated from ischemic hearts; however, the pH optimums of the enzymes from control and ischemic mitochondria were in the same range. After 1 day of chronic ischemia, the kinetics of the enzyme from ischemic mitochondria (compared with that of the enzyme from control mitochondria) showed marked changes in Vmax. Periods of ischemia longer than 1 day significantly decreased the K
m
of carnitine PCoAT for carnitine from 2.59 ± 0.476 mM to 0.713 ± 0.148 mM, and Vmax was still depressed (15 to 3 nmoles/min mg
-1
). The K
m
for palmitylCoA was not significantly affected. Arrhenius plots for the enzyme from ischemic (32 hours) mitochondria revealed a single phasic response to temperature change. Two nonintersecting slopes were characteristic of the normal 1-day ischemic and the normal sonicated activity. As a result of ischemia, changes in the lipid components in the membrane containing carnitine PCoAT were postulated: alterations in the hydrophobic environment of the enzyme produce interference in the binding of palmitylCoA to the second substrate site and may result in a decrease in the K
m
of the enzyme for carnitine. The single phasic response of the enzyme to temperature change may be additional evidence for membrane lipid alterations. A defect in the transport of long-chain fatty acids may be an early change associated with myocardial ischemia.
Effect of Calcium on Force-Velocity-Length Relations of Heart Muscle of the Cat
Authors: BRUTSAERT DIRK L. , CLAES VICTOR A. , GOETHALS MARK A.
Published: June 2012

The influence of calcium concentration in the bathing solution on the force-velocity relations of the isolated, electrically excited cat papillary muscle was examined. Shortening velocity was directly measured at minimum loads by unloading or load clamping the muscle from the preload (at the length, Lmax, where maximum active tensio was developed) to 0 (zero-load clamp), 2, 5, 10, and 15% of the total tension, P
0
. All measurements were made in the physiological length range between Lmax and 12.5% below Lmax. Increasing the calcium concentration augmented the measured maximum unloaded shortening velocity and shifted the normalized force-velocity relation when force was expressed as a fraction of P
0
. These observations suggest that the activating calcium has an action more complex than the binding to troponin alone.
Impaired Atrial Receptor Responses in Dogs with Heart Failure Due to Tricuspid Insufficiency and Pulmonary Artery Stenosis
Authors: GREENBERG TOKOKO T. , RICHMOND WILLIAM H. , STOCKING REGINALD A. , GUPTA PURSHOTIM D. , MEEHAN JOHN P. , HENRY JAMES P.
Published: June 2012

In a study of the effects of heart failure on the responses of cardiac receptors, ten dogs were subjected to tricuspid avulsion and pulmonary artery stenosis. One case of spontaneous heart failure was included in the series, and the electrical spike responses of atrial receptors to progressive changes in atrial stretch induced by infusion and hemorrhage were contrasted with those in normal control dogs. In the control dogs, the number of spikes per cycle increased very sharply with moderate, i.e., 5-10 cm H
2
O, venous pressure increments before reaching a maximum at 20 cm H
2
O. In the experimental dogs, the firing rate failed to increase to the same extent despite large increases in pressure. The resulting sets of curves exhibited a sharp dichotomy. This evidence for the impaired response of elements of the subendocardial receptor network is compatible with a decrease in the sensitivity of feedback mechanisms responsible for the regulation of sodium and water metabolism.
Reversal of Ouabain-Induced Electrophysiological Effects by Potassium Canrenoate in Canine Purkinje Fibers
Authors: YEH BILLY K. , LAZZARA RALPH
Published: June 2012

Canrenoate, an aldosterone antagonist, was administered to normal and ouabaintreated Purkinje fibers excised from the hearts of mongrel dogs and perfused with Tyrode's solution at 35-37°C. Intra- and extracellular potentials were recorded with conventional techniques. Potassium canrenoate in concentrations up to 1 x 10
-3
M or sodium canrenoate in concentrations up to 5 x 10
-3
M had inconspicuous electrophysiological effects on untreated Purkinje fibers. The duration of the action potential was slightly shortened. Amplitude of resting and action potentials, rate of rise of action potentials, conduction velocity, membrane responsiveness, automaticity, and excitability were not significantly altered by canrenoate. In contrast, potassium canrenoate in concentrations of 1 x 10
-4
M to 5 x 10
-4
M produced rapid restoration toward normal of fibers moderately or severely affected by ouabain (10
-7
M). Resting and action potentials were augmented, rate of rise of action potentials was increased, excitability was restored, and conduction was enhanced. Also ouabain-induced spontaneous rapid firing could be terminated. Twice equimolar doses of KCI were ineffective. The data suggest that canrenoate might be a specific antagonist to the electrophysiological effects of digitalis.
Impairment of the Diurnal Fibrinolytic Response in Man
Authors: ROSING DOUGLAS R. , REDWOOD DAVID R. , BRAKMAN PIETER , ASTRUP TAGE , EPSTEIN STEPHEN E.
Published: June 2012

Diurnal patterns of plasma euglobulin fibrinolytic activity, estimated by the fibrin plate method, were determined in groups of young normal and older normal subjects, in subjects with type IV hyperlipoproteinemia, and in subjects with coronary artery disease who had normal lipid profiles. The marked diurnal increases in fibrinolytic activity observed in the young normal subjects were significantly reduced in a large percent of the older normal subjects and in most of the subjects with coronary artery disease or type IV hyperlipoproteinemia. Although not conclusive, these findings were compatible with the hypothesis that an impairment in the responsiveness of the fibrinolytic system may be related to the development of coronary artery disease.
Measurement of Total Myocardial Blood Flow in Dogs with
43
K and the Scintillation Camera
Authors: ISHII YASUSHI , MACLNTYRE WILLIAM J. , PRITCHARD WALTER H. , ECKSTEIN RICHARD W.
Published: June 2012

To establish an innocuous method for evaluating myocardial ischemia, a technique was devised utilizing a scintillation camera to record the distribution of
43
K in the myocardium following an intravenous injection of the tracer. The objective was achieved by determining with the camera the fraction of the total amount of injected material deposited in the myocardium and calculating the total myocardial blood flow as a fraction of cardiac output according to the indicator fractionation principle. Following in vivo measurements in dogs, the entire heart was excised, compared with an aliquot of the injected dose as a standard, and assayed by a well scintillation counter. Reasonable agreement was achieved between estimations determined in vivo and those determined in vitro. Because of difficulties in ascertaining the heart border on the scans, a deconvolution program which used a digital computer was applied to the 40 x 40 matrix of digitized scan data to sharpen the transition between counting levels and improve the distributional image of
43
K deposition in the myocardium.
Adrenergic Control of the Peripheral Circulation in Cardiomyopathic Hamsters with Heart Failure
Authors: MARK ALLYN L. , MAYER HOWARD E. , SCHMID PHILLIP G. , HEISTAD DONALD D. , ABBOUD FRANCOIS M.
Published: June 2012

Adrenergic control of the peripheral circulation was studied in cardiomyopathic hamsters to determine if the functional status of terminal vascular sympathetic nerve endings is augmented in heart failure. Four groups of hamsters were studied: myopathic hamsters with heart failure (average age 296 days), myopathic hamsters without heart failure (average age 171 days), and two corresponding control groups of randomly bred hamsters matched for age. In hamsters with heart failure, the concentration of catecholamines in hearts, aortas, and femoral arteries was reduced compared with that in corresponding control hamsters. In myopathic hamsters without heart failure, the concentration of catecholamines was reduced in femoral arteries, but it was not reduced in hearts or aortas. Resting vascular resistance and vasoconstrictor responses to sympathetic nerve stimulation, norepinephrine, and angiotensin in the perfused hindquarters was reduced in hamsters with heart failure but not in myopathic hamsters without heart failure. These studies suggest that the functional status of terminal sympathetic nerve endings in blood vessels of the extremities is not augmented and may be reduced in this model of heart failure. Studies on other models of heart failure are needed to determine whether the absence of increased vascular catecholamines and the absence of augmented responses to sympathetic nerve stimulation are characteristic of heart failure in general or are unique to this model that has characteristics of highoutput failure.
Responsiveness of Isolated Cerebral and Peripheral Arteries to Serotonin, Norepinephrine, and Transmural Electrical Stimulation
Authors: TODA NOBORU , FUJITA YUZO
Published: June 2012

Spirally cut strips of cerebral and peripheral arteries from dogs were used for comparing the vasoconstricting effect of serotonin, norepinephrine, K
+
, and transmural electrical stimulation. Sensitivity of cerebral (basilar, posterior cerebral, and middle cerebral) arterial strips to serotonin was markedly greater than that to norepinephrine with respect to the median effective concentration (ED
50
) and the maximum response. Contractile responses of isolated human cerebral arteries to serotonin and norepinephrine were similar to those observed in the dog arteries. In contrast, proximal and distal strips from superior mesenteric arteries and strips from renal arteries were more sensitive to norepinephrine than they were to serotonin. Mean values of contractions caused by 5 x 10
-6
M serotonin relative to those caused by 30 mM K
+
in cerebral, internal carotid, external carotid, common carotid, and superior mesenteric arteries were in a descending order, whereas those for norepinephrine were in an ascending order. These studies demonstrate that a gradual transition occurs from characteristic responses seen in mesenteric arteries (high sensitivity to norepinephrine, low sensitivity to serotonin) to those seen in cerebral arteries (high sensitivity to serotonin, low sensitivity to norepinephrine). Transmural stimulation did not produce contractions of cerebral and internal carotid arteries, but contractions were produced in external carotid, common carotid, and superior mesenteric arteries. It appears that sympathetic nerves cannot play an important role in the regulation of vascular tone in large cerebral arteries.
Sympathetic Control of Canine Abdominal Aorta
Authors: GEROVÁ MÁria , GERO JÁN , DOLEŽEL SVATOPLUK , BLAŽKOVÁ-HuzulÁKOVÁ IDA
Published: June 2012

In anesthetized dogs the peripheral ends of the cut sympathetic chains (LG
1
-LG
2
level) were stimulated while blood pressure was held constant artificially, and the diameter of the abdominal aorta was monitored. Bilateral stimulation induced a reduction in diameter that was directly related to the stimulation frequency. Maximal diameter reduction of the aorta above the iliac bifurcation averaged 8.01±0.74% of resting diameter. The half-time of contraction (36.5±2.1 to 51.5±3.6 seconds) was indirectly related to the stimulation frequency. The effects of right or left sympathetic chain stimulation were quantitatively similar to each other (51.3±4.4% and 46.7±4.5%, respectively), and the response to bilateral stimulation (92.8±6.1%) did not differ from the calculated value for paired unilateral stimulation (100%). A significant proximo-distal gradient of response (below the branching off of the renal arteries 2.97±0.28%, at the midpoint 5.15±0.52%, and above the iliac bifurcation 8.56±0.79% of resting diameter) along the abdominal aorta was established during bilateral stimulation. Histochemical examination showed no corresponding differences in the density or the distribution of monoaminergic terminals. Dose-response relations for spiral strips taken from analogous aortic segments, however, displayed sensitivity to norepinephrine in the same order as the gradient in the in vivo experiments.
Nonlinear Analysis of Aortic Flow in Living Dogs
Authors: LING SUNG C. , ATABEK H. BÜLENT , LETZING WILLIAM G. , PATEL DALI J.
Published: June 2012

A nonlinear theory which considered the convective accelerations of blood and the nonlinear elastic behavior and taper angle of the vascular wall was used to study the nature of blood flow in the descending thoracic aorta of living dogs under a wide range of pressures and flows. Velocity profiles, wall friction, and discharge waves were predicted from locally measured input data about the pressure-gradient wave and arterial distention. Precision pressure-gradient waves free of static errors were obtained through forward and backward pressure-gradient measurements, and the arterial pressure-radius relation was obtained through cinematography using a telephoto lens. The results indicated that a major part of the mean pressure gradient was balanced by convective accelerations; the theory, which took this factor into account, predicted the correct velocity distributions and flow waves. The results also showed that for high flow rates the magnitude of the peak wall-shear stress became comparable to the yield stress of the endothelial surface and that radial flows of significant magnitude existed with respect to the arterial wall.
Multiple Pacemaker Sites in Spontaneously Active Vascular Muscle
Authors: HERMSMEYER KENT
Published: June 2012

Multiple-electrode extracellular recording was used to determine the degree to which membrane electrical activity spreads through the rat anterior mesenteric-hepatic portal vein. Glass-pore electrodes filled with physiological salt solution were placed against the isolated intact vein or longitudinal strips of vein at 1-mm intervals to record spontaneous spiking. No pressure electrode effect was found in the rat portal vein. Patterns and amplitudes of spiking indicated that spike activity was conducted for only a few millimeters. Multiple pacemaker sites and decremental conduction were found in both normal physiological solution and solution in which calcium concentration was halved or doubled and potassium concentration was doubled or tripled. An average of three or four pacemaker sites was found in all solutions. Approximate equipotential contours were constructed from a grid map of average spike amplitudes, and they showed the multiple regions of high-amplitude spiking, the nonuniform spatial decay of spike amplitude, and the shift of high-amplitude sites with time.
Mechanism for Flow Distribution in Normal and Ischemic Myocardium during Increased Ventricular Preload in the Dog
Authors: KJEKSHUS JOHN K.
Published: June 2012

The effects of increased ventricular preload on the distribution of regional blood flow in normal and ischemic myocardium were determined in deep and superficial regions of the left ventricle by using labeled microspheres. The ratio of flow in deep regions to flow in superficial regions in nonischemic tissue was 1.06 ± 0.06 and increased to 1.14 ± 0.06 when left ventricular end-diastolic pressure was raised from 4.8 ± 1 mm Hg to 18 ± 2 mm Hg by intravenous infusion of blood. In ischemic areas the ratio of flow in deep regions to flow in superficial regions fell simultaneously from 0.71 ± 0.12 to 0.45 ± 0.07 (
P
<0.001). Control of coronary flow during increased preload was studied in a separate preparation in which coronary flow was decreased in steps by reducing coronary perfusion pressure during periods of constant cardiac performance. The increased preload was associated with loss of autoregulation of coronary flow. It is suggested that, in myocardium with unrestricted coronary supply, regional distribution of flow is independent of gradients in tissue pressure during the described changes in preload due to an autoregulatory mechanism. However, when autoregulation of coronary flow is abolished by coronary artery occlusion, the coronary bed is fully dilated, and distribution of flow is directly dependent on gradients in myocardial tissue pressure. Increased ventricular preload consequently augments the underperfusion of the subendocardial regions of an ischemic area.
Role of the Adrenal Glands in the Development of Severe Hypertension
Authors: CARRETERO OSCAR A. , ENZMANN GARY , POLOMSKI CARL , PIWONSKA ALEXSANDRA , OZA NARENDRA B. , SCHORK ANTHONY
Published: June 2012

It has been previously shown that angiotensin II is involved in the pathogenesis of severe hypertension resulting from ligation of the aorta between the origins of the renal arteries. To see if part of the effect of the angiotensin II was due to the stimulation of mineralocorticoid secretion, blood pressure and plasma renin activity were studied after ligation of the aorta in adrenalectomized rats receiving maintenance doses of steroids. Rats subjected to adrenalectomy and aortic coarctation developed hypertension as severe as that in rats with intact adrenal glands. Thus, an increase in the secretory rate of adrenal hormones is not a pathogenetic factor in the development of severe hypertension after aortic coarctation.
Ventricular Conduction Delay and Arrhythmias during Regional Hyperkalemia in the Dog
Authors: ETTINGER PHILIP O. , REGAN TIMOTHY J. , OLDEWURTEL HENRY A. , KHAN MOHAMMAD I.
Published: June 2012

Coronary arterial potassium (K
+
) infusion induces RS-T elevation and ventricular arrhythmias. To explore electrical and metabolic events in this model, which simulates ischemia-induced injury currents and rhythm disturbances, isotonic KCl was infused at 0.5-2.0 ml/min into the left anterior descending or the left circumflex coronary artery of 37 intact anesthetized dogs. Conduction was monitored with His and left bundle branch recording catheters and with bipolar electrodes at endocardial and epicardial levels in the perfused zone. RS-T segments rose progressively in the perfused region despite normal coronary blood flow (
85
Kr) some dogs progressed rapidly to multifocal ventricular extrasystoles and ventricular fibrillation (group 1), but others continued for 20 minutes without developing fibrillation (group 2). His-Q and bundle branch conduction times were not altered by regional perfusion, but the QRS complex was locally prolonged. Ventricular extrasystoles were frequently coupled and left bundle branch depolarizations never preceded them, suggesting origin within the myocardium. Intramural electrodes showed increasing delay in the perfused region; epicardial depression was uniformly more profound and preceded significant arrhythmias, often with 2:1 or higher intramural block and slowing sufficient to allow reentry. Epicardial activation preceding endocardial activation was observed during extrasystoles in the perfused zone, further indicating origin within the myocardium. These phenomena were associated with tissue concentrations of K
+
in the outer wall significantly higher than those in the inner wall; and sodium was also significantly elevated. Therefore, it was postulated that reentry from depressed epicardial layers into more normal surrounding tissue constitutes a possible basis for the arrythmias in this model.
Effects of Increased Myocardial Oxygen Consumption on Coronary Reactive Hyperemia in the Awake Dog
Authors: BACHE ROBERT J. , COBB FREDERICK R. , GREENFIELD JOSEPH C.
Published: June 2012

This study was undertaken to determine whether coronary reactive hyperemia is coupled to myocardial metabolic activity and thus proportional to myocardial oxygen consumption or whether it is mechanically determined, resulting from direct myogenic relaxation of coronary vascular smooth muscle in response to loss of the stretch stimulus provided by arterial blood pressure. In ten unanesthetized dogs, coronary artery occlusions 1-7 seconds in duration produced reactive hyperemia resulting in 260-420% repayment of the blood flow debt incurred during occlusion. When myocardial oxygen consumption and coronary blood flow were increased by paired ventricular stimulation, reactive hyperemia increased to a commensurate degree so that debt repayments remained unchanged at 270-420%. That this augmentation of reactive hyperemia was actually related to increased myocardial metabolic activity during the occlusion was demonstrated by a similar increase in the hyperemic response when paired ventricular stimulation was applied during the occlusion only. To demonstrate that augmented reactive hyperemia during paired ventricular stimulation did not merely represent direct myogenic relaxation imposed on a vascular bed more dilated from the onset, coronary blood flow was increased by infusion of adenosine with no increase in myocardial oxygen consumption. During adenosine infusion, the total volume of reactive hyperemic blood flow was similar to that observed during the control situation. Thus, in the coronary system reactive hyperemia is related to myocardial metabolic activity during the interval of arterial occlusion and not influenced by alterations in resting coronary blood flow which occur independently of myocardial oxygen consumption.
Spontaneous and Induced Cardiac Arrhythmias in Subendocardial Purkinje Fibers Surviving Extensive Myocardial Infarction in Dogs
Authors: FRIEDMAN PETER L. , STEWART JAMES R. , WIT ANDREW L.
Published: June 2012

The cellular electrophysiological mechanisms underlying the ventricular arrhythmias that accompany myocardial infarction were studied in isolated, superfused infarcted myocardium excised from dogs previously subjected to a two-stage ligation of the anterior descending coronary artery. Ventricular arrhythmias frequently occurred in the intact heart 24 hours after coronary occlusion. Surviving subendocardial Purkinje fibers in infarcts excised at this time were highly arrhythmic when they were studied with intracellular microelectrodes in vitro. These arrhythmias consisted of rapid, repetitive depolarizations and occurred spontaneously or could be induced by premature electrical stimulation. Premature stimulation also resulted in single unstimulated responses. In such instances, premature impulses conducted extremely slowly through the infarcted region where surviving Purkinje fiber action potential durations were extraordinarily prolonged. Conduction block at some sites in the infarct caused phenomena which were interpreted as reentrant beats. Some surviving subendocardial Purkinje fibers in the infarct demonstrated spontaneous diastolic depolarization and appeared to function as pacemakers in the absence of electrical stimulation. In some instances, these fibers constituted typical parasystolic foci, demonstrating both entrance and exit block. These results suggest that subendocardial Purkinje fibers which survive in an infarct may be the site of origin of some of the ventricular arrhythmias that accompany myocardial infarction.
Inhibition of Adrenergic Outflow to Peripheral Blood Vessels by Vagal Afferents from the Cardiopulmonary Region in the Dog
Authors: MANCIA GIUSEPPE , DONALD DAVID E. , SHEPHERD JOHN T.
Published: June 2012

In closed-chest atropinized dogs anesthetized with chloralose and ventilated artificially, the aortic nerves were cut beneath the nodose ganglion, and the carotid sinuses were either denervated or vascularly isolated and maintained at a pressure of 40 mm Hg. Denervation was established by the failure of the pressoreceptor systems to respond to mechanical stimulation. Cold block or section of the cervical vagi resulted in statistically significant increases in arterial blood pressure (18%), heart rate (3%), central venous pressure (13%), hind-limb perfusion pressure (12%), pressure within the occluded spleen (18%), and efferent renal sympathetic nerve activity (28%). There was no change in saphenous vein perfusion pressure. The vascular responses were abolished by a-receptor blockade and were not affected by section of the vagi at the diaphragm. When the pressure in the vascularly isolated innervated carotid sinuses was varied from 40 to 220 mm Hg, the vascular responses to vagal block decreased steeply between 100 and 160 mm Hg and were absent at 200 mm Hg. Thus, receptors in the cardiopulmonary region with afferent vagal fibers exert a continuous restraint on the sympathetic adrenergic outflow to resistance and capacitance vessels, especially when the input from the carotid baroreceptors is decreased.
Arterial Baroreceptor Activity in Rabbits with Experimental Atherosclerosis
Authors: ANGELL-JAMES JENNIFER E.
Published: June 2012

A total of 16 rabbits developed atherosclerosis after receiving a diet containing 1% cholesterol and 6% sunflower seed oil for up to 67 weeks. Their mean blood pressure rose from 85 to 114 mm Hg. The aortic arch region was isolated and perfused with Krebs-Henseleit solution, and the impulse activity of 70 single aortic and 8 right subclavian baroreceptor fibers was studied during step increases and decreases in perfusion pressure. The threshold pressure of the aortic baroreceptor fibers from the atherosclerotic rabbits was only slightly higher (
P
> 0.4) than that of 29 fibers from 17 normal rabbits, but the impulse frequency was less (
P
< 0.02). The gradient of the impulse frequency-pressure curves (0.73 impulses/sec mm Hg
-1
), was significantly lower (
P
< 0.01) than normal (1.19 impulses/sec mm Hg
-1
), as was the gradient of the curves from the right subclavian baroreceptor region. The curves resulting from first increasing and then decreasing the perfusion pressure were more separated in the atherosclerotic rabbits than they were in the normal rabbits. There was a correlation between the amount of the reduction in the sensitivity of the aortic baroreceptors and the length of time the rabbits had been on the lipemic diet (
r
= 0.96). The changes in the baroreceptor activity were associated with a reduction in the distensibility of the perfused area and with histological lesions in the baroreceptors and the arterial walls. The mild hypertension in the atherosclerotic rabbits could partly be accounted for by the reduction in aortic baroreceptor activity. Similar mechanisms might contribute to blood pressure anomalies in humans with atherosclerosis.
Effective Compliance of the Total Vascular Bed and the Intrathoracic Compartment Derived from Changes in Central Venous Pressure Induced by Volume Changes in Man
Authors: ECHT MARTIN , DÜWELING JOHANNES , GAUER OTTO H. , LANGE LOTHAR
Published: June 2012

In eight male subjects the blood volume was changed (± 10%) by hemorrhage and transfusion. One cycle of blood infusion and withdrawal or hemorrhage and reinfusion was completed within 9 minutes. The effective compliance of the total circulation was calculated from the changes in central venous pressure recorded simultaneously with the changes in blood volume. The effective compliance was 2.3 ml/mm Hg kg
-1
body weight. This procedure was repeated while the capacity of the circulatory system was restricted by infusion of norepinephrine (15 µg/min), lower body positive pressure, or both. The compliance values thus obtained were: norepinephrine 1.7 ml/mm Hg kg
-1
body weight, lower body positive pressure 1.2 ml/mm Hg kg
-1
body weight, and both norepinephrine and lower body positive pressure 0.9 ml/mm Hg kg
-1
body weight. The effective compliance of the intrathoracic vascular bed was assumed to be between 1.2 ml/mm Hg kg
-1
body weight (lower body positive pressure) and 0.9 ml/mm Hg kg
-1
body weight (norepinephrine and lower body positive pressure). These values constitute 55% and 42% of the effective compliance of the total circulation, respectively.
Role of the Cerebellum and the Vestibular Apparatus in Regulation of Orthostatic Reflexes in the Cat
Authors: DOBA NOBUTAKA , REIS DONALD J.
Published: June 2012

The contribution of the fastigial nucleus and the vestibular nerves (eighth cranial nerves) to the orthostatic reflexes in anesthetized, paralyzed cats was studied. Bilateral lesions of the rostral fastigial nucleus resulted in impairment of the reflex changes in blood pressure, femoral arterial flow, and resistance evoked by head-up tilting to 30° or 60°. The deficit consisted of an increase in the magnitude of the initial fall in blood pressure during tilting. The effects on blood pressure were paralleled by decreased vasoconstriction in the femoral artery. Extracranial lesions of the vestibular nerves produced comparable deficits which were not enhanced by subsequent lesions of the fastigial nucleus. Denervation of the baroreceptors impaired the reflexes, and subsequent lesion of the fastigial nucleus increased this deficit. The pressor response evoked by electrical stimulation of the rostral fastigial nucleus also reversed the deficit in orthostasis produced by hemorrhage. Small doses of sodium pentobarbital which did not alter the resting blood pressure or the pressor response to carotid occlusion impaired the responses to stimulation of the fastigial nucleus and tilting. Therefore, the rostral fastigial nucleus, which might be triggered by the vestibular apparatus, appears to participate in concert with the baroreceptors in the initiation and possibly the maintenance of the orthostatic reflexes.
Regional Myocardial Blood Flow in Lambs with Concentric Right Ventricular Hypertrophy
Authors: ARCHIE JOSEPH P. , FIXLER DAVID E. , ULLYOT DANIEL J. , BUCKBERG GERALD D. , HOFFMAN JULIEN I. E.
Published: June 2012

Chronically hypertrophied right ventricles function normally under high systolic pressures, whereas normal right ventricles fail when they are acutely subjected to similar pressures. This phenomenon may be partly due to adaptation of the coronary circulation as well as to hypertrophy. Knowledge of the magnitude and distribution of coronary blood flow and the degree of coronary vascular reserve are important in understanding the function of hypertrophied myocardium. We studied these variables in 16 awake, 5-12-week-old, tranquilized lambs; 9 of the lambs had had their main pulmonary artery banded at 2 days of age. Pressures, cardiac output, and coronary blood flow (radioactive microsphere method) were measured at rest and during two stress states--isoproterenol and dextran infusion. Ventricular function was similar in control and banded lambs. We found significant right ventricular hypertension and both right ventricular and septal hypertrophy in the banded lambs. Total coronary blood flow per gram was slightly higher in banded lambs in all states, and right ventricular flow per gram was significantly elevated at rest and during isoproterenol infusion. Right ventricular coronary resistance per gram was significantly lower in banded lambs in all states. These changes demonstrate that hypertrophied right ventricular tissue is not ischemic at rest, since there is vascular reserve. The changes also raise the question of increased vascularity in hypertrophied myocardium. Right ventricular oxygen supply per unit oxygen demand was increased in banded lambs at rest and during isoproterenol infusion. This finding suggests that hypertrophied myocardium has inefficient oxygen utilization, low oxygen extraction, or both.
Characteristics of the Cholesterol-Esterifying Activity in Normal and Atherosclerotic Rabbit Aortas
Authors: HASHIMOTO SAM , DAYTON SEYMOUR , ALFIN-SLATER ROSLYN B. , BUI PHIET T. , BAKER NOME , WILSON LEON
Published: June 2012

Esterification of cholesterol with [1-
14
C]palmityl-CoA by an atherosclerotic cell-free homogenate was approximately 16-50-fold greater than that by a normal cell-free homogenate for a given amount of protein in the homogenate. This difference was due to hyperactivity of the cholesterol-esterifying system in the atherosclerotic cell-free homogenate rather than to depletion of radioactive palmityl-CoA in the reaction mixture containing normal homogenate. Neither an activator of cholesterol esterification in the soluble fraction of the atherosclerotic aortic homogenate nor an inhibitor in the soluble fraction of the normal aortic homogenate could be demonstrated. The pH optimum within the pH range covered for esterification and the apparent K
m
values were approximately the same in normal and atherosclerotic microsomes, suggesting that the enzymes were probably the same. The results suggested a higher concentration or a higher activity of the enzyme in or on atherosclerotic microsomes. An alternative possibility is that high concentrations of free cholesterol in the atherosclerotic microsomes were responsible for the augmented cholesterol esterification. This possibility seems unlikely, because the observed 2.3-fold increase in the free cholesterol concentration should not produce a 25-fold increase in cholesterol esterification. The rate of cholesterol esterification by atherosclerotic microsomes varied with the substrate: oleyl-CoA > palmityl-CoA > linoleyl-CoA.
Reflex Venoconstriction and Capacity Vessel Pressure-Volume Relationships in Dogs
Authors: DREES JOHN A. , ROTHE CARL F.
Published: June 2012

Reflexogenic control of vascular capacity was studied by measuring the mean circulatory pressure (P

MC

) at various blood volumes. P

MC

was obtained by fibrillating the heart for 10 seconds and rapidly transferring blood from the aorta to the vena cava until the pressures equilibrated. It was measured 0.5, 2, and 5 minutes after randomized changes in blood volume of 0 to ± 30% of the control volume in chloralose-urethane anesthetized dogs. Active venoconstriction was suppressed by administering hexamethonium and enhanced by administering norepinephrine. The effective total vascular compliance, expressed as the reciprocal of the slopes of P

MC

vs
. blood volume curves in the controls, was linear. Compliance values differed significantly from each other and increased between 0.5, 2, and 5 minutes after a change in blood volume (2.60, 3.47, and 4.17 ml/kg body weight mm Hg
-1
, respectively). With ganglionic blockade, only an 8-ml/ kg hemorrhage was required to bring P

MC

from the control level of 7.8 mm Hg to 4 mm Hg within 0.5 minutes. With reflexes intact, a 17-ml/kg hemorrhage reduced P

MC

from a control of 10.7 mm Hg to 4 mm Hg. To maintain this pressure for 5 minutes, an additional 8.2 and 9.1 ml/kg, respectively, had to be hemorrhaged, suggesting that the compensation after about 30 seconds was mostly from passive viscoelastic creep and fluid shifts. Less than half of the compensation for hemorrhage during the first 5 minutes came from the reflex venoconstriction.
Initiation of Sustained Rhythmic Activity by Single Propagated Action Potentials in Canine Cardiac Purkinje Fibers Exposed to Sodium-Free Solution or to Ouabain
Authors: CRANEFIELD PAUL F. , ARONSON RONALD S.
Published: June 2012

Canine cardiac Purkinje fibers were exposed to sodium-free solutions containing 128 mM tetraethylammonium chloride and 16.2 mM calcium. Some fibers exposed to these solutions were spontaneously active. Other fibers were quiescent, but they could be thrown into sustained rhythmic activity by a single driven action potential; the sustained activity resulted from the depolarizing phase of an oscillatory after-potential. Premature action potentials often showed prolonged plateaus, and their repolarization continued to a more negative level than that seen during the regular sustained activity. This condition caused a temporary slowing of rhythm and, on rare occasions, a cessation of spontaneous activity. Other canine cardiac Purkinje fibers were exposed to normal Tyrode's solution containing 0.125 mg ouabain/liter. In such fibers driven activity caused progressive loss of resting potential. Concomitant with that loss of resting potential, oscillatory after-potentials appeared. These oscillatory after-potentials sometimes grew into sustained rhythmic activity that occurred at a level of resting potential at which the normal sodium-dependent upstroke was presumably inactivated.
Hydrolysis of Bradykinin by Angiotensin-Converting Enzyme
Authors: DORER FREDERIC E. , KAHN JOSEPH R. , LENTZ KENNETH E. , LEVINE MELVIN , SKEGGS LEONARD T.
Published: June 2012

Two dipeptides, phenylalanylarginine (Phe-Arg) and serylproline (Ser-Pro), are released sequentially from bradykinin by angiotensin-converting enzyme purified from hog lungs; chloride increases the rate of release of both dipeptides. Using an automated ninhydrin-reagent method, we studied the kinetics of bradykinin hydrolysis. The reaction proceeded in the absence of chloride; however, the addition of chloride increased the rate of hydrolysis by decreasing K
m
and increasing V
m
. The K
m
values for bradykinin were 3.9 x 10
-6
M in the absence of chloride and 0.85 x 10
-6
M in the presence of 0.01m NaCl (optimal concentration). Both of these K
m
values were well below the value of 30 x 10
-6
M determined for angiotensin I at its optimal chloride concentration of 0.1M. Hydrolysis of bradykinin had a pH optimum of 7 and was inhibited by low concentrations (10
-6
M) of ethylenediaminetetraacetic acid or the nonapeptide pyroglutamyl (Pyr)-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro. It is concluded that one enzyme, acting as a dipeptidyl carboxypeptidase, catalyzes both the conversion of angiotensin I to angiotensin II and the hydrolysis of bradykinin.
Regression of Left Ventricular Dilation and Hypertrophy after Removal of Volume Overload
Authors: PAPADIMITRIOU JOHN M. , HOPKINS BARRY E. , TAYLOR ROGER R.
Published: June 2012

Gross and ultrastructural changes occurring in the left ventricle in response to chronic volume overload were studied in dogs. One group of dogs was examined 28-43 days after an aortocaval fistula had been created; congestive heart failure had developed at the time of the examination. Two other groups of dogs were investigated 78 ± 17 (
SD
) days and 178 ± 4 days after similar fistulas had been closed. A group of control dogs was also studied. Aortocaval fistulas produced significant left ventricular dilation and hypertrophy. Ultrastructural changes included enlargement and distortion of intercalated disks, increase in number but decrease in size and relative volume of mitochondria, and loss of lateral alignment of sarcomeres. Left ventricles, 78 days after the fistulas had been closed, were not different ultrastructurally or grossly from those in dogs with patent fistulas. After 178 days of closure, ventricular mass and volume had decreased; mass was still significantly greater than that in normal dogs, but cavity volume was not. Ultrastructural abnormalities in dogs after 178 days of closure were much less marked than those in dogs with patent fistulas, and ultrastructure was hardly distinguishable from normal. The findings in these experiments indicate that gross and ultrastructural abnormalities produced in the left ventricle by chronic volume overload are largely, if not completely, reversible.
Importance of Atrial Compliance in Cardiac Performance
Authors: SUGA HIROYUKI
Published: June 2012

Effects of changes in atrial compliance on cardiac performance were analyzed using a circulatory analog model. The atrium was assumed to be a noncontracting chamber with a constant compliance. It connected the venous return system, which was represented by mean circulatory filling pressure and a venous return resistance in accordance with Guyton's concept, with the ventricle, which was characterized by a time-varying elasticity. Atrial compliance was increased from near zero to a value at which atrial volume was twice ventricular stroke volume, while the parameters of ventricular contractility were kept unchanged. Cardiac output increased from 2,400 to 3,240 ml/min with increases in atrial compliance from 0.1 to 20 ml/mm Hg (venous return resistance 0.1 mm Hg sec/ml), whereas mean atrial pressure simultaneously decreased from 3.0 to 2.2 mm Hg. This result indicates that cardiac performance in terms of the cardiac output-mean atrial pressure relationship was markedly improved by increases in atrial compliance in spite of constant ventricular contractility. The analysis of the model strongly suggests that natural atrial compliance in situ, by pooling venous return flow during systole and supplying it to the ventricle during diastole, facilitates the transformation of the continuous venous return flow into the intermittent ventricular filling flow.