bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of heart rate on myocardial blood flow in dogs with left ventricular hypertrophy
Authors: Vrobel T. R. , Ring W. S. , Anderson R. W. , Emery R. W. , Bache R. J.
Published: December 2017

Because of the previous suggestion that subendocardial perfusion may be inadequate in the hypertrophied heart, this study was carried out to examine the response of transmural myocardial blood flow to pacing induced tachycardia in dogs with chronic left ventricular hypertrophy. Myocardial hypertrophy, produced by banding the ascending aorta of puppies at 5-6 wk of age, resulted in an 87% average increase in relative left ventricular mass compared with the control dogs. Myocardial blood flow was examined during ventricular pacing at heart rates of 100, 200, and 250 beats/min using radionuclide-labeled microspheres. Mean blood flow per unit myocardial mass was similar in the two groups of dogs at a heart rate of 100 beats/min and increased regularly during pacing in both groups of animals. Increasing heart rates did not change the transmural pattern of myocardial blood flow in the normal dogs, but in the animals with left ventricular hypertrophy pacing at 250 beats/min resulted in a significant redistribution of perfusion away from the subendocardium, with the ratio of subendocardial/subepicardial blood flow falling from 1.03 +/- 0.08 at 100 beats/min to 0.83 +/0 0.06 at 250 beats/min (P < 0.01). This redistribution of blood flow away from the subendocardium was especially marked in the regions encompassing the papillary muscles and the intervening left ventricular lateral wall.
Sensitization of cardiac receptors (vagal afferents) by intracoronary acetylstrophanthidin
Authors: Thames M. D. , Waickman L. A. , Abboud F. M.
Published: December 2017

The purpose of this study was to determine if sensitization of cardiac receptors with acetylstrophanthidin augments the inhibition of renal nerve activity resulting from expansion of the blood volume or from coronary artery occlusion. Ten chloralose-anesthetized dogs with sinoaortic baroreceptor denervation were subjected to volume expansion with dextran in saline. Under control conditions, volume expansion resulted in decreases in renal nerve activity (% or control) that were inversely related to left atrial pressure (-13.0%/mmHg left atrial pressure). After intracoronary acetylstrophanthidin, volume expansion resulted in a significantly greater suppression of renal nerve activity (-20.6%/mmHg). Occlusion of the circumflex coronary artery in 19 dogs with carotid baroreceptor denervation resulted in a 29 +/- 5% (SE) reduction in renal nerve activity. After intracoronary acetylstrophanthidin, circumflex occlusion resulted in a significantly greater decrease in renal nerve activity (45 +/- 4%). Vagotomy abolished the decreases in renal nerve activity, which resulted from volume expansion and from circumflex coronary occlusion. These data show that volume expansion and coronary occlusion reflexly decrease renal nerve activity via cardiac afferent vagal endings. These reflex inhibitory influences are augmented after intracoronary acetylstrophanthidin. The results are consistent with the view that intracoronary acetylstrophanthidin sensitizes cardiac afferent vagal endings.
Effects of graded hypoxia on contraction of cultured chick embryo ventricular cells
Authors: Barry W. H. , Pober J. , Marsh J. D. , Frankel S. R. , Smith T. W.
Published: December 2017

The quantitative relationship between a given decrease in O2 tension (Po2) and the degree of depression of contractile function is difficult to define in intact myocardial tissues because of uncertainty in estimation of diffusion limitations. We therefore have studied the effects of hypoxia on contractility in a system with minimal series diffusion barriers, consisting of single cells within spontaneously contracting monolayers cultured from 10-day-old chick embryo ventricles. Reversible decreases in amplitude and velocity of cell wall motion occurred over a 3- to 4-min period when perfusate Po2 was less than 12 mmHg, and a maximum depression to about 30% of control levels occurred at Po2 values less than 4 mmHg. On reoxygenation, recovery of amplitude and velocity of contraction occurred in less than 15 s. Inhibition of glycolysis with 0.1 mM iodoacetate resulted in a more marked decrease in contraction amplitude and a significant slowing of beating rate during hypoxia. In addition, the critical Po2 at which contractile function became impaired was increased to about 16 mmHg. Thus, high-energy phosphates derived from anaerobic glycolysis appear to be able to support a reduced level of contractility during brief periods of hypoxia in these cultured heart cells.
Myocardial infarction in dogs with chronic hypertension and left ventricular hypertrophy
Authors: Mueller T. M. , Tomanek R. J. , Kerber R. E. , Marcus M. L.
Published: December 2017

Chronic hypertension increases the risk of myocardial infarction and the morbidity and mortality associated with it. Although accelerated atherosclerosis is partially responsible, other abnormalities in the coronary circulation associated with hypertension, such as decreased coronary vascular capacity and capillary density, could also contribute. To evaluate the effects of these nonatherosclerotic abnormalities, we produced sudden coronary occlusion in nine chronically hypertensive dogs. The mean aortic pressure and left ventricular mass were about 50% greater in hypertensive dogs than in the nine controls. Before occlusion and 5 min and 49 h after occlusion, myocardial blood flow was measured with tracer microspheres. Also, the extent of infarction in selected myocardial segments was quantified histologically. We found that coronary occlusion reduced flows to a similar extent, and that, over a 48-h period, collateral flow increased to a similar extent in the two groups. In addition, the amount of necrosis associated with a given degree of ischemia was similar in the two groups. Although the extent of the left ventricle that became ischemic was greater in the hypertensive dogs (28 +/- 2 vs. 18 +/- 4%; P < 0.05), chronic hypertension and left ventricular hypertrophy did not limit the recruitment of collateral supply or increase the amount of necrosis associated with a given degree of ischemia.
Hemodynamic and metabolic responses to repeated blood sampling in the rat
Authors: Walsh G. M. , Ferrone R. A. , Tsuchiya M. , Woods E. F. , Deland E. C.
Published: December 2017

Repeated blood sampling (0.2 ml) in the conscious rat during the course of 10 cardiac index measurements using the Fick procedure did not alter the cardiac index as measured initially (285 ml x min-1 x kg-1). However, oxygen consumption and hematocrit were reduced 7-19% and 4-14%, respectively. Replacement of blood removed during sampling with donor blood prevented these responses, but also led to reduced cardiac index and arterial oxygen content, 22-28% and 10-21%, respectively. In additional studies in anesthetized rats, hemorrhage (25 ml/kg) increased plasma K+ by 29% and reduced plasma Na+ by 3%, suggesting that compensatory fluid replacement originated in cells as well as interstitium. This fluid replacement after blood loss helps sustain normal systemic hemodynamics, but blood loss can produce metabolic alterations that should be taken into account in any biochemical study. Although metabolic alterations can be prevented by replacing lost blood with donor blood, cardiopulmonary function may be adversely affected.
Participation of regional sympathetic outflows in the centrogenic pulmonary pathology
Authors: Chen H. I. , Lin J. D. , Liao J. F.
Published: December 2017

In anesthetized and vagotomized rats, a mechanical cerebral compression (CC) evoked systemic arterial hypertension (SAH) and pulmonary venous hypertension (PVH) followed by massive pulmonary hemorrhagic edema (PHE). The hemodynamic and pulmonary changes induced by CC were more pronounced in the right heart bypass (RHB) preparation (venous return to reservoir and constant pulmonary inflow). Additional observations in RHB included a marked reduction in reservoir volume (RV) without significant change in pulmonary vascular resistance (PVR). In either natural circulation or RHB, an upper thoracic sympathectomy did not affect the SAH, RV reduction, and PVR change, but reduced the PVH and PHE by approximately one-third. Such effects were not attributed to cardiac denervation, because beta 1-adrenergic blockade (metaprolol) did not alter the CC-induced PHE. Splanchnic denervation greatly diminished the SAH and prevented the RV reduction, PVH, and PHE. The results suggest that the centrogenic PHE is initiated from an intense arteriolar constriction, principally in the splanchnic beds. The latter causes left heart failure leading to volume and pressure loading and blood loss in the lungs. Direct sympathetic impulses to the lungs do not affect the PVR and RV changes and are not essential for the genesis of PHE. However, they may alter the vascular compliance and thereby exacerbate the PVH and PHE when passive accumulation of blood is produced in the lungs.
Rapid-freezing transmural cardiac biopsy drill
Authors: Allard J. R. , Conhaim R. L. , Vlahakes G. J. , O'Neill M. J. , Hoffman J. I.
Published: December 2017

We have built a transmural cardiac biopsy drill that uses an air turbine (10,000 rpm) to turn a stainless steel bore of either 2.0 or 4.5 mm diam. Vacuum draws the cut biopsies through the drill into isopentane chilled to -150 degrees C with liquid nitrogen. The steel bores cut through the beating canine left ventricular free wall in 0.14 +/- 0.04 (SD) permitting sampling in discrete portions of the cardiac cycle. Small and large biopsies traverse the drill in 0.48 +/- 0.19 and 0.15 +/- 0.04 s, respectively. Large biopsies freeze in 1.46 +/- 0.73 s, whereas small biopsies are calculated to freeze in 0.28 s. Average biopsy weights are 34 +/- 14 and 180 +/- 71 mg. Left ventricular myocardial blood flow measured with radionuclide-labeled microspheres showed that muscle plugs sutured into wound sites of 4.5-mm-diam biopsies cause a 30% reduction in myocardial blood flow within 0.5 cm of the biopsy site. Light microscopy shows normal cardiac muscle with little damage from drill rotation.
Effects of volume expansion and vasodilators in acute pericardial tamponade
Authors: Gascho J. A. , Martins J. B. , Marcus M. L. , Kerber R. E.
Published: December 2017

Pharmacologic therapy may be useful as emergency treatment for acute pericardial tamponade while preparing for pericardiocentesis. We studied the effects of volume expansion and vasodilators in acute pericardial tamponade in spontaneously breathing mongrel dogs. Hemodynamic parameters and blood flow (15-micrometer microspheres) to brain, heart, kidney, colon, stomach, liver, and temporalis muscle were measured. Arterial pressure and cardiac output rose, and blood flow to all major organs, except stomach, increased after volume expansion (n = 17) by infusion of 20 ml/kg of dextran after tamponade. With nitroprusside (8-75 microgram/min) after volume expansion (n = 5), ventricular filling pressures were reduced to control levels, whereas the favorable effects of volume expansion on cardiac output, blood pressure, and kidney and heart blood flow were maintained. Hydralazine alone or hydralazine plus volume expansion was not as effective as the combination of nitroprusside and volume expansion. Thus, volume expansion alone or the combination of volume expansion and nitroprusside infusion should be beneficial as emergency therapy while preparing for pericardiocentesis in patients with acute pericardial tamponade.
Blockade of frontocortical-brain stem pathway prevents ventricular fibrillation of ischemic heart
Authors: Skinner J. E. , Reed J. C.
Published: December 2017

The hypothesis tested was that functional blockade of a pathway known to travel from the frontal cortex through the posterior hypothalamus to the brain stem might prevent the occurrence of ventricular fibrillation (VF) in the ischemic heart of conscious stressed pigs. The hypothesis was based on previous findings that 1) psychological stress is a necessary factor for the initiation of VF in the ischemic heart of conscious pigs, 2) the frontal cortex and its related thalamic gating mechanism, uniquely show neuroelectric responses to stressful stimuli, and 3) direct electric stimulation of either the frontal cortex, posterior hypothalamus, or fields of Forel will produce ventricular arrhythmias and myocardial necrosis. In the present study it was found that cryogenic blockade of the forebrain, posterior hypothalamus, or fields of Forel prevents or delays VF after left anterior descending coronary artery occlusion in conscious stressed pigs (P less than 0.01). Blockade of control structures adjacent to these loci in another group of pigs had no effect on VF latency. Neither heart rate nor electroencephalographic changes could explain the differences between the groups. The results show that blockade of the frontocortical-brain stem pathway prevents the lethal consequences of myocardial ischemia in stressed animals.
Angiotensin-induced relaxation in isolated dog renal and cerebral arteries
Authors: Toda N. , Miyazaki M.
Published: December 2017

Helically cut strips of dog renal and cerebral (basilar and middle cerebral) arteries contracted with prostaglandin (PG) F2 alpha relaxed in response to angiotensin II (AII; 10(-9) to 10(-7) M) in a dose-dependent manner. In renal arterial strips, the relaxation was preceded by a transient contraction. Both the relaxation and the contraction induced by AII were suppressed by [Sar1,Ala8]AII or [Sar1,Ile8]AII. Treatment with propranolol, atropine, hexamethonium, cocaine, aminophylline, cimetidine, or ouabain failed to alter the relaxing effect of AII. The peptide-induced relaxation was reversed to a contraction by aspirin or indomethacin. Treatment with tranylcypromine or 15-hydroperoxy arachidonic acid suppressed the relaxation induced by AII in renal and cerebral arteries but did not alter relaxations induced by PGI2 or K+ (5 mM). In experiments with superfused dog renal and coronary arteries and rat stomach strips, the renal arteries in response to AII released a prostaglandin like substance; the release was suppressed by [Sar1,Ala8]AII or indomethacin. It appears that the relaxation of isolated dog renal and cerebral arteries induced by AII is mediated by the release of PGI2, which is associated with stimulation of AII receptors.
Excitation-contraction coupling in hypothermic ischemic myocardium
Authors: Hess M. L. , Krause S. M. , Robbins A. D. , Greenfield L. J.
Published: December 2017

The excitation-contraction coupling system of the global ischemic hypothermic myocardium was studied by evaluating the functional integrity of the isolated sarcoplasmic reticulum (SR) and myofibrils and determining glycogen decay 30 and 60 min after the onset of surgically induced global ischemia. Calcium uptake by the SR from both the 30- and 60-min groups was depressed (control 0.940 +/- 0.05, 30 min 0.430 +/- 0.033, 60 min 0.535 +/- 0.033 mumol Ca2+ . mg-1 . min-1; P less than 0.001). In contrast SR Ca2+-ATPase activity was not different in the three groups (control 1.150 +/- 0.080, 30 min 1.468 +/- 0.025, 60 min 1.338 +/- 0.199 mumol Pi . mg-1 . min-1; P greater than 0.2). Glycogen decay in the hypothermic group was depressed compared to control (control 7.52 +/- 2.01, 30 min 6.152 +/- 1.16, 60 min 5.814 +/- 1.76 mumol glycogen/mg myocardium; P less than 0.05). Myofibrillar pCa-ATPase curves in both hypothermic ischemic groups were depressed (maximal ATPase activity; control 0.160 +/- 0.028, 30 min 0.1130 +/- 0.01, 60 min 0.127 +/- 0.008 mumol Pi . mg-1 . min-1; P less than 0.01). Kinetic analysis of the myofibrillar pCa-ATPase data, utilizing double-reciprocal plots, demonstrated an increase in Km for the hypothermic ischemic groups. It is concluded that the excitation-contraction coupling system of the hypothermic ischemic myocardium at 1 h is characterized by a defect in the calcium transport system of the sarcoplasmic reticulum with preservation of the Ca2+-ATPase, a depression of the myofibrillar ATPase activity, a decrease in affinity, and the preservation of adequate glycogen stores. It is hypothesized that these defects may explain an observed depression in myocardial function following reperfusion.
Direct effects of gram-negative endotoxin on skeletal muscle glucose uptake
Authors: Raymond R. M. , Harkema J. M. , Emerson T. E.
Published: December 2017

The effect of locally infused endotoxin on gracilis muscle glucose uptake was determined in anesthetized mongrel dogs. Locally infused endotoxin consistently caused an increase in skeletal muscle glucose uptake with no alterations in any other metabolic variable. These data demonstrate that endotoxin can act locally to increase glucose uptake by skeletal muscle, independent of the action of insulin or other metabolic factors. On the other hand, when endotoxin was given systemically to induce shock, gracilis muscle glucose uptake did not increase. These differences may reflect the reduction in plasma endotoxin concentration mediated by the reticuloendothelial system (RES). However, live Escherichia coli shock was associated with an increase in glucose uptake in the constant flow perfused gracilis muscle after 4.5 h of shock. We believe this increase in muscle glucose uptake resulted from the direct effects of endotoxin, the plasma concentration of which presumably increased as the RES was overwhelmed and became less effective. The contribution of this phenomenon to the hypoglycemia of gram-negative endotoxin or septic shock cannot be evaluated from this study.
Pulmonary injury and prostaglandin production during endotoxemia in conscious sheep
Authors: Demling R. H. , Smith M. , Gunther R. , Flynn J. T. , Gee M. H.
Published: December 2017

Prostaglandins F2 alpha, E2, and I2 (as 6-keto-PGF1 alpha) and TxA2 (as TxB2) were measured by radioimmunoassay in plasma and lymph from 12 conscious sheep with chronic lung lymph fistulas given Escherichia coli endotoxin (2-10 micrograms/kg) and followed for 24 h. Endotoxin produced a two-phase pulmonary injury. Phase 1 was characterized by transient severe pulmonary hypertension and increased lymph flow rate (QL). Plasma and lymph PGF2 alpha concentrations increased from base-line values of 0.13 +/- 0.08 and 0.30 +/- 0.10 ng/ml to 0.96 +/- 0.37 and 2.8 +/- 0.80 ng/ml, respectively. Values for TxB2 increased from 0.7 +/- 0.1 to 5.5 +/- 1.1 ng/ml in lymph and to 3.2 +/- 0.6 in plasma. Plasma PGI2 increased from 0.48 +/- 0.29 to 4.97 +/- 1.21 ng/ml and lymph PGI2 from 1.80 +/- 0.73 to 14.19 +/- 2.79 ng/ml. Phase 2 was characterized by moderately elevated pulmonary vascular pressures and a maintained high flow rate of protein-rich lymph. Lung lymph and plasma PGF2 alpha concentrations returned to base line. Lymph PGI2 decreased significantly to 5.23 +/- 2.47 ng/ml, whereas plasma PGI2 decreased to 2.70 +/- 1.07 ng/ml. We conclude that prostaglandins, particularly PGF2 alpha and prostacyclin, are released from the lung after endotoxemia and appear in lung lymph as sensitive indicators of pulmonary microvascular injury. Prostanoid production appears to temporally correspond with changes in the pulmonary microcirculation.
Role of sinoaortic reflexes in hemodynamic patterns of natural defense behaviors in the cat
Authors: Baccelli G. , Albertini R. , Del Bo A. , Mancia G. , Zanchetti A.
Published: December 2017

To evaluate whether sinoaortic afferents contribute to the hemodynamic pattern of fighting, cardiovascular changes associated with fighting were studied in cats before and after sinoaortic denervation. Sinoaortic denervation exaggerates the decrease in heart rate, cardiac output, and arterial pressure during immobile confrontation (hissing, staring but no movement). During nonsupportive fighting (fighting with forelimbs while lying on one side) and supportive fighting ( fighting while standing on four feet) sinoaortic denervation reduces the increase in heart rate and cardiac output, minimizes the mesenteric vasoconstriction, induces a fall in arterial blood pressure, but does not affect iliac vasoconstriction or vasodilatation. The hemodynamic pattern of fighting is similarly changed by temporary inactivation of carotid sinus baroreflexes by common carotid occlusion as by chronic section of sinoaortic nerves. It is concluded that sinoaortic reflexes play an important role in the cardiovascular patterns accompanying natural fighting. They favor cardiac action and allow a marked visceral vasoconstriction to occur, thus minimizing or preventing a fall in blood pressure during emotional behavior.
Release of acetylcholine in the isolated heart
Authors: Loffelholz K.
Published: December 2017

This article summarizes methods for studying release of acetylcholine (ACh) in the heart and reviews the literature on release, synthesis, and inactivation of ACh. Cholinergic mechanisms involved in cardiac neuroeffector transmission are, in principle, the same as in ganglia and motor endplates, but their relative functional significance exhibits unique features. First, release of ACh evoked by nerve stimulation is maintained at a high level due to rapid formation of free extracellular choline from phospholipids. Choline derived from ACh hydrolysis plays a minor role in ACh synthesis. The constant efflux of choline allows continuous monitoring of changes in formation and removal of extracellular choline, e.g., by activation of neuronal uptake during nerve stimulation. Second, ACh released from terminal nerve fibers is rapidly washed into the circulation and thereby escapes hydrolysis by cholinesterase activity to a functionally significant extent. Hydrolysis and diffusion appear as equally important mechanisms of transmitter inactivation in the heart. The cardiac neuroeffector junction is not a morphological or functional entity restricted to adjacent pre- and postsynaptic elements.
Relaxing effect of pharmacologic interventions increasing cAMP in rat heart
Authors: Vittone L. , Grassi A. , Chiappe L. , Argel M. , Cingolani H. E.
Published: December 2017

The relationship between cAMP and relaxation was studied in the isolated rat heart beating at constant rate and perfused at constant coronary flow. After treatment during 1 min with different positive inotropic interventions, cyclic nucleotide levels (cAMP and cGMP) and cAMP-dependent protein kinase activity were determined in heart homogenates. Glucagon, norepinephrine, and isoproterenol increased cAMP from 0.503 +/- 0.025 pmol/mg wet wt to 1.051 +/- 0.099, 0.900 +/- 0.064, and 0.982 +/- 0.138, respectively. Simultaneously glucagon, norepinephrine, and isoproterenol increased cAMP-dependent protein kinase activity ratio from 0.21 +/- 0.02 to 0.45 +/- 0.04, 0.33 +/- 0.02, and 0.34 +/- 0.02, respectively. The ratio between maximal velocities of contraction and relaxation (+T/-T) was significantly decreased by these interventions, whereas time to peak tension (TTP) was shortened by norepinephrine and isoproterenol. High calcium, ouabain, and paired stimulation did not affect cAMP levels, TTP, or +T/-T. A striking correlation was found between cAMP-dependent protein kinase activity and relaxation induces, i.e., TTP, -T, or +T/-T (r = +/- 0.7 to -0.9). Results suggest that inotropic interventions increasing cAMP levels might be primarily affecting intracellular mechanisms causing relaxation.
Influence of exercise on excitation-contraction coupling in rat myocardium
Authors: Tibbits G. F. , Barnard R. J. , Baldwin K. M. , Cugalj N. , Roberts N. K.
Published: December 2017

The present studies were conducted to investigate further the mechanisms by which the myocardium adapts to exercise training. Sixty female rats were randomly divided into sedentary control (group C) and trained (group T) groups. Group T was progressively trained for 12 wk. After the rats were killed, left ventricular papillary muscles were mounted in a tissue bath for mechanical studies. Muscles from group T generated greater peak isometric twitch tension per unit cross-sectional area than muscles from group C with [Ca2+]o ranging from 0.25 to 3.5 mM. Analyses of these data indicated that the Km for Ca2+ was not different but that the predicted number of sarcolemmal Ca2+ binding sites was 63% higher in group T. The ATPase activity of the purified cardiac myofibrils was not different between the two groups in the pCa range of 8.53-4.42. Action potentials were recorded with microelectrodes impaled into left ventricular muscle fibers of the subendocardium. Although there was no difference in the resting membrane potential, overshoot, or 90% duration, there was a significant prolongation of the action potential at 0 mV (20.2 +/- 1.0 vs 30.0 +/- 1.3 ms) in group T. These data further support the hypothesis that treadmill exercise enhances cardiac performance by increasing Ca2+ availability to the contractile element. This adaptation is mediated, at least in part, by a sarcolemmal adaptation induced by the exercise paradigm.
Mechanism of coronary vasoconstriction induced by carbocyclic thromboxane A2
Authors: Smith E. F. , Lefer A. M. , Nicolaou K. C.
Published: December 2017

The mechanism of carbocyclic thromboxane A2 (CTA2) vasoconstriction was studied in thoracic aortic strips and isolated perfused cat coronary arteries. CTA2, a stable thromboxane analog, produced coronary constriction at 50 pg/ml or greater. At constant flow, 5 ng/ml CTA2 increased perfusion pressure 40 +/- 4 mmHg. The calcium antagonist nifedipine reduced CTA2-induced vasoconstriction by 8% at 1 ng/ml (NS), 22% at 10 ng/ml (NS), 65% at 100 ng/ml (P less than 0.01), and 75% at 1,000 ng/ml (P less than 0.005). Other calcium antagonists also significantly reduced CTA2-induced coronary constriction. Inhibition of vasoconstriction by calcium antagonists was not due to direct thromboxane-receptor antagonism, inasmuch as nifedipine did not prevent CTA2-induced contraction in cat aortas, vessels that are not dependent on external calcium for contraction. Reducing external Ca2+ concentration to 0.63 mM significantly reduced coronary constriction over most of the CTA2 concentration-response range. Phentolamine (1-50 micrograms/ml), phenoxybenzamine (1-100 micrograms/ml), and saralasin (0.1-10 micrograms/ml) were all without significant effect on CTA2-induced coronary constriction. The results indicate that the mechanism of thromboxane coronary vasoconstriction is by a specific thromboxane receptor that is dependent on an inward calcium flux. The data also suggest that the efficacy of calcium antagonists in coronary vasospasm may be related to their ability to noncompetitively inhibit thromboxane-induced vasoconstriction.
Inhibition of carotid pressor response by left aortic depressor nerve in dogs
Authors: Walgenbach S. C. , Donald D. E. , Melcher A.
Published: December 2017

In 12 conscious dogs, the mean increase of 26 mmHg in arterial pressure during carotid occlusion was augmented by 52 mmHg after section of the left cervical vagus nerve and 6 mmHg after right vagal section. In 18 anesthetized dogs, in which the cervical vagal nerves were reversibly cold blocked, corresponding values were 33, 28, and 6 mmHg, respectively. In nine of these dogs, this left-sided dominance was present after bilateral section of the vagal cardiopulmonary afferents; it was absent after bilateral section of the aortic nerves in the other nine dogs. In five dogs on cardiopulmonary bypass with heart and lungs excluded, pressure within the isolated aorta and major intrathoracic arteries was raised from 120 to 220 mmHg. The resultant hypotension reflexly induced by activation of aortic baroreceptors was reduced by left but not by right vagal cold block. It was concluded that, in the dog, the left aortic nerve provided the major inhibition of the increase in arterial pressure after carotid occlusion.
Regulation of coenzyme A synthesis in heart muscle: effects of diabetes and fasting
Authors: Reibel D. K. , Wyse B. W. , Berkich D. A. , Neely J. R.
Published: December 2017

Regulation of coenzyme A (CoA) synthesis was studied in the isolated perfused rat heart. Incorporation of [14C]pantothenic acid ([14C]PA) into CoA was determined to estimate rates of CoA synthesis. Although CoA levels were elevated in hearts removed from fasted and diabetic animals, in vitro rates of CoA synthesis were not elevated. The presence of 1.2 mM palmitate, 5 mM pyruvate, or 10 mM beta-hydroxybutyrate in the perfusate-reduced PA incorporation into CoA in control hearts by 40, 60, and 80%, respectively. Insulin (25 mU/ml) reduced incorporation by 90%. The alterations in CoA synthesis in hearts perfused with buffer containing palmitate, pyruvate, beta-hydroxybutyrate, and insulin were associated with no change in myocardial PA uptake. Data indicate that these substrates and insulin inhibit the first step in the pathway of CoA synthesis, pantothenate kinase. Because insulin is a strong inhibitor of CoA synthesis in vitro, decreased circulating levels of insulin in fasted and diabetic animals may account for the increased levels of CoA in vivo.
Contrasting reflex influences of cardiac afferent nerves during coronary occlusion
Authors: Weaver L. C. , Danos L. M. , Oehl R. S. , Meckler R. L.
Published: December 2017

Afferent neurons contained within cardiac sympathetic nerves may have important influences on the circulation when activated during myocardial ischemia. Although such activation is known to reflexly excite upper thoracic sympathetic efferent neurons, effects on other components of sympathetic outflow are unknown. Therefore, cardiac sympathetic afferent nerves were stimulated by occlusion of coronary arteries to investigate their reflex influences on renal sympathetic nerve activity and systemic arterial blood pressure. Responses were observed in anesthetized cats in which sympathetic and/or vagal cardiac afferent nerves remained intact and arterial baroreceptors remained intact or had been denervated. Stimulating sympathetic afferent neurons caused excitation of renal nerve activity, which was accompanied by variable changes in arterial pressure. Stimulation of vagal afferents by coronary occlusion consistently produced inhibition of renal nerve activity and marked depressor responses. When both components of cardiac innervation remained intact, increases or decreases in renal nerve activity and blood pressure were elicited by coronary artery occlusion in the presence or absence of arterial baroreceptors. These results illustrate that cardiac sympathetic afferent nerves can contribute significantly to cardiovascular control during myocardial ischemia.
Exogenous substrate utilization in Ca2+-tolerant myocytes from adult rat hearts
Authors: Montini J. , Bagby G. J. , Burns A. H. , Spitzer J. J.
Published: December 2017

A preparation of isolated noncontracting adult rat heart myocytes can be obtained in which viability is high, yield is adequate, and the cells are not sensitive to the deleterious effects of Ca2+ at physiological levels. Myocytes are enzymatically dispersed and maintained in a medium containing amino acids and 1% bovine serum albumin at 37 degrees C. The initial viability of 77% fell to 70% after a 60-min incubation in the presence of 1.5 mM Ca2+. The initial cellular ATP content of the myocytes was 27 nmol/mg protein. Cellular ATP content fell to 21 and 17 nmol/mg protein when cells were incubated for 60 min with and without 1.5 mM Ca2+, respectively. The oxidation of glucose and lactate was increased by 50 and 30%, respectively, by the addition of Ca2+. A decrease in the oxidation rate of these two substrates was noted when the myocytes were incubated with medium containing ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid. No changes in the rate of palmitate oxidation were observed. The significant increase in glucose and lactate oxidation due to ca2+ provides further evidence that ca2+ influences myocardial substrate utilization independent of its effects on mechanical performance of the myocardium.
Autonomic nervous system and cellular injury from circumflex ligation in dogs
Authors: Elson J. J. , Ten Eick R. E. , Singer D. H.
Published: December 2017

The role of the autonomic nerves in the development of irreversible cellular injury (ICI) after circumflex coronary occlusion was examined in dogs with intact, acutely, or chronically decentralized cardiac nerves. Cardiac nerves were chronically decentralized 2 wk before ligation (CD) or acutely at the time of ligation (AD). In one group of AD dogs, the beta-blocker oxprenolol (0.3 mg/kg) was administered before ligation (AD + Ox). Hearts were paced at 160 beats/min to exclude any contribution of rate change secondary to autonomic intervention. The results are expressed in terms of percent of the cross-sectional area of the posterior papillary muscle (PPM) sustaining ICI after 40-min occlusion: intact 64 +/- 4% (SE), 6 +/- 4%, AD 39 +/- 10%, and AD + Ox 2 +/- 2%. Both acute and chronic denervation protect against ICI even in the absence of changes in heart rate. Furthermore, in dogs with intact cardiac nerves, reduction in pacing rate from 160 to 60 beats/min also decreased the extent of ICI from 64 +/- 4 to 34 +/- 10%. Experiments defining the time course of development of ICI in the PPM indicate that protection was only temporary, delaying the onset of injury by 25 min. These findings suggest that 1) neural activity in extrinsic cardiac sympathetic nerves activate beta-receptors, thereby influencing the development of ICI, and 2) differences in protection afforded by acute denervation with and without beta-blockade indicated that intrinsic postganglionic sympathetic nerve terminals can liberate transmitter in response to ischemia even in the absence of extrinsic neural activity.
Glutathione peroxidase, selenium, and prostaglandin synthesis in platelets
Authors: Doni M. G. , Avventi G. L. , Bonadiman L. , Bonaccorso G.
Published: December 2017

Glutathione peroxidase (GSH-Px) contains 4 selenium atoms/molecule; its activity is increased by selenium dietary intake. The enzyme destroys H2O2 and organic hydroperoxides, contributing to the integrity of biological membranes. GSH-Px activity increased (+100%) in washed platelets of rats administered selenium (0.3 ppm given as sodium selenite) for 60 days from 10.44 +/- 1.10 U/g protein (control rats fed a standard diet) to 20.50 +/- 1.21 U/g protein (mean +/- SE; P less than 0.001). GSH-Px in washed erythrocytes was also stimulated (+70%) after 80 days of selenium dietary intake from 11.60 +/0 0.82 U/g Hb to 19.74 +/- 0.94 U/g Hb (P less than 0.001). Malondialdehyde (MDA), the typical breakdown product of peroxidized lipid and a suitable indicator of platelet prostaglandin production, increased from 0.343 +/- 0.035 nM/3 X 10(8) platelets (control) to 0.478 +/- 0.052 nM/3 X 10(8) platelets after 30 days of selenium treatment (P less than 0.05) and to 0.527 +/- 0.051 nM/3 X 10(8) platelets after 80 days (P less than 0.01). MDA was measured by the thiobarbituric acid method after stimulation with 25 X 10(-4) M arachidonic acid. It is concluded that platelets are very rich in GSH-Px, i.e., activity is greatly increased by oral administration of selenium and that the synthesis of prostaglandins is stimulated too.
Role of vasopressin, catecholamines, and plasma volume in hypertonic saline-induced hypertension
Authors: Hatzinikolaou P. , Gavras H. , Brunner H. R. , Gavras I.
Published: December 2017

Elevation of blood pressure induced by an acute sodium and fluid load in the anephric state has been attributed to intravascular fluid volume expansion. The present experiments were designed to study the role of vasopressin and catecholamines in this type of hypertension. Normotensive anephric rats, adrenergically intact or pretreated with alpha- and beta-adrenoceptor blockade, and deoxycorticosterone (DOC)-salt-treated anephric rats, intact or pretreated with alpha- and beta-adrenoceptor blockade, received an infusion of 2 ml containing 3 meq NaCl, followed by intravenous administration of an analogue antagonist of the vasopressor effect of arginine-vasopressin (AVP). Pressure increments induced by hypertonic saline were abolished by an AVP antagonist partly in the adrenergically intact animals (leaving a small residual pressure elevation) and completely in adrenergically blocked animals, which had a larger AVP component. Volumes expansion did not necessarily accompany increase in blood pressure after saline infusion. In fact some DOC-salt-treated animals with the highest blood pressures and norepinephrine levels exhibited contraction of plasma volume. Increments in blood pressure were negatively correlated with plasma volume changes (r = -0.687, P less than 0.05) in these animals and positively with norepinephrine levels in all adrenergically intact animals (r = 0.818, P less than 0.001). It is concluded that the hypertensive response elicited by acute hypertonic saline load is due to vasoconstriction mediated partly by vasopressin and partly by the sympathetic system, which may in some way attenuate the effect of vasopressin.
Measurement of left and right ventricular volume from implanted radiopaque markers
Authors: Santamore W. P. , Carey R. , Goodrich D. , Bove A. A.
Published: December 2017

To better understand biventricular mechanics, an algorithm was developed to simultaneously calculate right and left ventricular volumes from randomly placed subendocardial radiopaque markers. Mathematically, the ventricle is represented as a stack of circular discs. The radius R of each disc is calculated as the distance from the subendocardial radiopaque marker to a computer generated base-to-apex line, and the height H of each disc is determined by the projected distance between radiopaque markers along the base-to-apex line. Accordingly, the volume (V) is calculated as V = pi . sigma Hi . Ri2. The validity of this algorithm was tested on 10 canine left ventricular casts, on 10 human right ventricular casts, and in five experiments. For the left ventricle, the regression line between the casts (VT) and calculated (VC) volumes was VC = 0.55 VT + 6.6, with r = 0.95, standard error of estimate (Sy) = 1.9 ml, and the standard deviation of percent error = 12.6%. For the right ventricle, VC = 1.75 VT = 42.5, with r = 0.86, Sy = 16.2 ml, and the standard deviation of percent error = 24.8%. In five animal experiments, radiopaque markers were implanted into the endocardium of the left and right ventricles and comparisons were made between angiographic- and marker-determined ventricular volumes. For the five experiments, the mean correlation coefficient, relating the marker volumes to the angiographic volumes, were 0.92 +/- 0.01 for the left ventricle and 0.89 +/- 0.02 for the right ventricle. The results, which are similar to other volume-determination methods, indicate that this method can be applied to determine right and left ventricular volume. Once implanted, fluoroscopy of these markers provides a noninvasive means of calculating ventricular volume.
Muscle and nonmuscle cell RNA polymerase activities in early myocardial hypertrophy
Authors: Cutilletta A. F.
Published: December 2017

RNA polymerase was solubilized from separated rat cardiac muscle and nonmuscle cells during the development of myocardial hypertrophy 1 or 3 days after sham operation or aortic constriction. Six fractions of enzymes designated IA, IB, IIA, IIB, IIIA, and IIIB were identified by DEAE-Sephadex chromatography in each cell population. Fractions designated IA and IB, IIA and IIB, and IIIA and IIIB were similar to RNA polymerase I, II, and III, respectively, found in other eukaryotes. Muscle cell enzyme activity from sham-operated and aortic-constricted rats did not significantly differ 1 day after intervention. By 3 days there was a significant increase in the activity of each enzyme fraction in muscle cells from aortic-constricted rats. There was a slight increase in IIA activity in nonmuscle cells from aortic-constricted rats at 1 day. By 3 days after aortic constriction RNA polymerase IIA, IIB, and IIIB activities increased in nonmuscle cells, but no change was noted in nonmuscle RNA polymerase IA, IB, and IIIA. Changes in RNA polymerase activities in cardiac muscle and nonmuscle cells occur during the development of myocardial hypertrophy but do not appear to correlate with reported changes in RNA synthesis. chromatin-template activity, however, did increase in cardiac muscle cells at both 1 and 3 days after aortic constriction. A similar increase was not seen in nonmuscle cell chromatin-template activity until 3 days. These data suggest that the initial increase in RNA synthesis during the development of myocardial hypertrophy is related to changes in chromatin-template activity in muscle cells. The activities of the RNA polymerase increase after a short delay and vary in their response.
Effect of thyroid hormone on canine cardiac Purkinje fiber transmembrane potential
Authors: Jaeger J. M. , Houser S. R. , Freeman A. R. , Spann J. F.
Published: December 2017

The electrophysiological effects of chronic 3,5,3'-triiodo-L-thyronine (T3) administration on cardiac Purkinje fibers were studied using intracellular recording techniques. Adult mongrel dogs receiving T3 injections (1 mg/kg sc) three times daily for 7-12 days demonstrated elevated resting heart rates and serum total T3 content, atrophied thyroid glands, and a small body weight loss when compared with controls. Isolated Purkinje fibers from control and T3-treated animals were superfused with an oxygenated Tyrode solution containing 4 mM K+ at 35 degrees C. Preparations were stimulated externally at 1.0, 2.0, and 3.1 Hz for 2-3 min while measurements of action potentials were made. At 1.0 Hz, action potential duration (APD) of T3-treated Purkinje fibers was significantly (P less than 0.01) greater than controls at both 20% (APD20) and 80% (APD80) of repolarization to the maximum diastolic potential (Emax). The overshoot, plateau height, and Emax were not different. Raising the stimulus frequency to 2.0 and 3.1 Hz produced a slight increase in the overshoot and a rate-dependent shortening of the action potential duration until it resembled controls. APD20 shortened proportionately more than APD80, giving the action potential a triangular appearance. The K+ selectivity of the resting membrane was not affected as evidenced by Nernst plots, which were identical in normal and T3-treated fibers. These results demonstrate that thyroid hormone influences the action potential of isolated cardiac Purkinje fibers.
Transmural distribution of blood flow during activation of coronary muscarinic receptors
Authors: Gross G. J. , Buck J. D. , Warltier D. C.
Published: December 2017

The role of coronary muscarinic receptors in the distribution of transmural blood flow across the left ventricular wall of the working heart was studied in anesthetized open-chest dogs. Tissue blood flow in subepicardium, midmyocardium, and subendocardium was determined with radioactive microspheres before and during activation of muscarinic vasodilator receptors by intracoronary infusions of acetylcholine. Myocardial and coronary vascular beta-receptors were blocked by sotalol (2.0 mg/kg iv). Equivalent submaximal coronary vasodilator doses of acetylcholine and adenosine were compared for effects on transmural blood flow. Intracoronary infusions of acetylcholine (5.0 and 10.7 micrograms/min) produced a dose-related increase in the subendocardial-subepicardial blood flow ratio (endo/epi) from 1.07 to 1.32 and 1.57, respectively. A progressively larger decrease in coronary vascular resistance occurred in the subendocardium than midmyocardium or subepicardium following acetylcholine administration. In contrast, intracoronary administration of adenosine (54.4 micrograms/min) produced no change in endo/epi. Atropine effectively blocked acetylcholine-induced coronary vasodilation but not vasodilation produced by adenosine. Neither agent affected heart rate, left ventricular pressure, coronary perfusion pressure, or myocardial contractility. These results suggest that activation of muscarinic coronary vasodilator receptors redistributes blood flow preferentially to the subendocardium independent of cardiac mechanical influences.
Contractile dysfunction of atrial myocardium from endotoxin-shocked guinea pigs
Authors: Parker J. L. , Adams H. R.
Published: December 2017

Atrial muscle isolated from guinea pigs subjected to Escherichia coli endotoxin shock was used to study the myocardial changes associated with this experimental disease state. Isometric contractile tension and its first derivative (dT/dt) consistently were depressed by about 45% in muscle from the shock group (P less than 0.001), but contraction time intervals of the shock tissues were not significantly altered. The inotropic deficit of shock was completely antagonized by high concentrations of Ca2+ (greater than 4.5 mM). However, the maximal positive inotropic response to increased frequency of stimulation (0.1-2.2 Hz) only partially antagonized shock-induced cardiac depression. Heart muscle from shocked animals exhibited increased sensitivity to the negative inotropic effects of Mn2+, low Ca2+, and gentamicin; recovery from the depressant actions of these agents was prolonged 3.6- to 4.8-fold in shock. However, the negative inotropic potency of slow Ca2+ channel blockers, D 600 and nifedipine, was unaffected by shock. Similarly, studies with an isoproterenol-activated slow Ca2+ channel technique demonstrated equivalent inotropic responses of shock and control heart muscle. Present data provide evidence for a disruption of myocardial Ca2+ metabolism associated with endotoxin-induced inotropic depression of the heart but suggest that slow Ca2+ channels of the sarcolemma remain functional in this disease state.
Different sites of adenosine formation in the heart
Authors: Schutz W. , Schrader J. , Gerlach E.
Published: December 2017

In an attempt to further define the site of myocardial adenosine formation, isolated guinea pig hearts were perfused with potent inhibitors of 5'-nucleotidase [alpha, beta-methylene adenosine 5'-diphosphate (AOPCP)] and of nucleoside transport [4-nitrobenzyl thioinosine (NBMPR)]. AOPCP (50 microM) inhibited the activity of cardiac ecto-5'-nucleotidase by 85% but did not influence the release of adenosine, inosine, and hypoxanthine formed at an accelerated rate by the heart during hypoxic perfusion (30% O2). In contrast, NBMPR (5 microM) diminished the hypoxia-induced release of adenosine and its degradatives and greatly potentiated the increase of myocardial tissue levels of respective purine compounds. Studies carried out with 5'-deoxyadenosine, an adenosine derivative that is not metabolized, indicate NBMPR to inhibit both uptake and release of adenosine in the isolated heart and in human erythrocytes. Cell fractionation studies on guinea pig ventricular muscle revealed that 5'-nucleotidase, though mainly associated with the membrane fraction, is also found in the cardiac cytosol (200,000-g supernatant), exhibiting a different substrate specificity. Furthermore, S-adenosylhomocysteine hydrolase as well as adenosine kinase and adenosine deaminase proved to be exclusively present in the cytosolic fraction. Our findings suggest that in the hypoxic heart a) ecto-5'-nucleotidase most likely is not involved in the formation of adenosine, b) release of adenosine from the heart requires adenosine to be transported across the sarcolemma membrane, and c) adenosine is predominantly formed intracellularly, a process involving cytosolic 5'-nucleotidase and/or S-adenosylhomocysteine hydrolase.