bluuebunny/crossref_metadata_2025 huggingface dataset:
Two classes of ouabain binding sites in ferret heart and two forms of Na+-K+-ATPase
Authors: Ng Y. C. , Akera T.
Published: December 2017

In partially purified Na+-K+-adenosinetriphosphatase (ATPase) obtained from ferret heart, ouabain produced a monophasic inhibition curve; however, the curve spanned over 5 logarithmic units, indicating the presence of more than one classes of enzyme. [3H]ouabain binding studies revealed high-and low-affinity binding sites in approximately equal abundance, with apparent dissociation constants of 10 and 230 nM, respectively. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of phosphoenzyme formed from [gamma-32P]ATP showed two distinct K+-sensitive bands of approximately 100,000 molecular weight. Phosphoenzyme formation from the high-molecular-weight alpha(+) form was selectively inhibited by N-ethylmaleimide. Ouabain caused a 50% inhibition of phosphorylation of the alpha(+) form at 40 nM and the lower-molecular-weight alpha form at 300 nM. In papillary muscle preparations, 1-30 nM ouabain produced a modest positive inotropic effect that reached an apparent plateau at 30 nM. Further increases in ouabain concentrations, however, produced additional and prominent inotropic effects at 0.1-10 microM. These results indicate for the first time in cardiac muscle that the high- and low-affinity ouabain binding sites are associated with the alpha(+) and alpha forms of the Na+-K+-ATPase, respectively, and that binding of ouabain to either of these sites causes enzyme inhibition and the positive inotropic effect.
Cardiac sympathetic nerve activity and catecholamine kinetics in cat hearts
Authors: Honda T. , Ninomiya I. , Azumi T.
Published: December 2017

To understand the catecholamine kinetics in the heart during hypotension, we simultaneously measured cardiac sympathetic nerve activity (CSNA), concentrations of norepinephrine (NE) and epinephrine (Epi) in arterial and coronary sinus blood, and coronary sinus plasma flow in 11 cats. With hypotension, NE and Epi concentrations in arterial blood increased more than those in coronary sinus blood. The arteriovenous difference between NE and Epi concentrations increased, whereas coronary sinus plasma flow decreased. The net cardiac uptake of NE from coronary arterial blood was not significant (0.826 +/- 0.506 ng/min) under the control condition. With hypotension, it increased significantly to 9.658 +/- 3.182 ng/min (P less than 0.05) in spite of a CSNA increase to 302.0 +/- 30.3% of that during the control condition. The net cardiac uptake of Epi was significant (1.574 +/- 0.542 ng/min) under the control condition, and, with hypotension, it increased significantly to 4.721 +/- 1.049 ng/min (P less than 0.01). We concluded that during hypotension NE was supplied to the heart from sympathetic nerve endings distributing to the heart and also from coronary arterial blood.
Atrial natriuretic peptide increases resistance to venous return in rats
Authors: Chien Y. W. , Frohlich E. D. , Trippodo N. C.
Published: December 2017

To examine mechanisms by which administration of atrial natriuretic peptide (ANP) decreases venous return, we compared the hemodynamic effects of ANP (0.5 microgram X min-1 X kg-1), furosemide (FU, 10 micrograms X min-1 X kg-1), and hexamethonium (HEX, 0.5 mg X min-1 X kg-1) with those of vehicle (VE) in anesthetized rats. Compared with VE, ANP reduced mean arterial pressure (106 +/- 4 vs. 92 +/- 3 mmHg; P less than 0.05), central venous pressure (0.3 +/- 0.3 vs. -0.7 +/- 0.2 mmHg; P less than 0.01), and cardiac index (215 +/- 12 vs. 174 +/- 10 ml X min-1 X kg-1; P less than 0.05) and increased calculated resistance to venous return (32 +/- 3 vs. 42 +/- 2 mmHg X ml-1 X min X g; P less than 0.01). Mean circulatory filling pressure, distribution of blood flow between splanchnic organs and skeletal muscles, and total peripheral resistance remained unchanged. FU increased urine output similar to that of ANP, yet produced no hemodynamic changes, dissociating diuresis, and decreased cardiac output. HEX lowered arterial pressure through a reduction in total peripheral resistance without altering cardiac output or resistance to venous return. The results confirm previous findings that ANP decreases cardiac output through a reduction in venous return and suggest that this results partly from increased resistance to venous return and not from venodilation or redistribution of blood flow.
Effects of dihydropyridines on stress, myosin phosphorylation, and V0 in smooth muscle
Authors: Moreland S. , Moreland R. S.
Published: December 2017

Contraction of swine carotid medial fibers with KCl results in stress development associated with high levels of myosin light chain (MLC) phosphorylation and maximum shortening velocity (V0) indicative of rapidly cycling phosphorylated cross bridges. The period of stress maintenance is characterized by low levels of MLC phosphorylation and V0; the maintained stress is postulated to be supported by dephosphorylated, slowly cycling cross bridges (latch bridges). This study was designed to examine the roles of calcium in both stress development and stress maintenance. Medial strips were contracted with 110 mM KCl in the presence of varying concentrations of the calcium channel blocker nifedipine (1-100 nM) or were contracted with varying concentrations of the calcium channel activator BAY-K 8644 (0.3-3 microM). Nifedipine significantly depressed stress maintenance and V0, but had little effect on either stress development or MLC phosphorylation. Conversely, BAY-K 8644 produced contractions that were equal to those elicited with 110 mM KCl but that were characterized by low levels of V0 and basal or low levels of MLC phosphorylation. These data suggest that the mechanisms by which the cellular calcium concentration increases and the limitations on this increase may impact differently on different regulatory processes of contraction and, thereby, on cross bridge behavior.
Reflex regulation of atrioventricular conduction
Authors: Warner M. R. , Loeb J. M.
Published: December 2017

We evaluated the time course of baroreflex modulation of atrioventricular (AV) nodal conduction in anesthetized dogs (n = 28). Beat-by-beat changes in heart rate (HR) and AV interval (AVI) evoked by transient alterations in arterial pressure (AP) were recorded in the intact state, after vagotomy, and following stellectomy. Under each experimental condition, alterations in AP induced parallel changes in HR and AVI with maximum HR and AVI responses occurring simultaneously. In three animals, AP alterations elicited pacemaker shifts that markedly altered AVI. Reflex changes in AVI were also examined during atrial pacing. When pacing at a low (120 beats/min) versus a high (190 beats/min) level of heart rate, reductions in AP decreased AVI to a significantly lower absolute value in the intact state, after vagotomy, and following stellectomy. However, under each experimental condition, decreases in AP elicited marked changes in AVI at either level of pacing. We conclude that baroreflex-induced changes in sympathetic and parasympathetic activity influence the sinoatrial and AV nodes simultaneously, predominate over the effects of changes in HR at the AV node, and may induce pacemaker shifts that influence the measurement of AVI.
Maximum myocardial oxygen transport during anemia and polycythemia in dogs
Authors: Baer R. W. , Vlahakes G. J. , Uhlig P. N. , Hoffman J. I.
Published: December 2017

The purpose of this study was to determine the effect of hematocrit changes on coronary pressure-flow relations during maximum vasodilation to define the relative importance of changes in hemoglobin concentration, blood viscosity, and perfusion pressure in determining maximum myocardial oxygen transport. An anemic group and a polycythemic group of dogs were studied under halothane anesthesia at the hematocrit extremes and after serial exchange transfusions to intermediate hematocrits. Circumflex pressure-flow relations were generated at each hematocrit during maximum pharmacological vasodilation (adenosine 20 micrograms X kg-1 X min-1 or chromonar 8 mg/kg). Maximal coronary vascular conductance (incremental conductance) decreased in an approximately linear fashion with increasing hematocrit. Maximum myocardial oxygen transport showed an "inverted U-shape" relation to hematocrit with the peak occurring at or slightly above normal hematocrit. Hemoglobin concentration, viscosity, and perfusion pressure were all found to be physiologically important determinants of maximal myocardial oxygen transport. Given normal perfusion pressure, arterial oxygen saturation, and myocardial oxygen extraction, we found that maximum myocardial oxygen delivery greatly exceeds the level necessary to supply basal myocardial oxygen needs at all hematocrits studied.
Tolerance to hypoxia of myocardium from adult and aged spontaneously hypertensive rats
Authors: Brooks W. W. , Ingwall J. S. , Conrad C. H. , Holubarsch C. , Bing O. H.
Published: December 2017

Myocardial mechanics and high-energy phosphate content [ATP and creatine phosphate (CrP)] of isolated left ventricular papillary muscle preparations from male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were compared at 6 and 18 mo of age. In comparison with oxygenated (95% O2-5% CO2) glucose-supplied (5.5 mM) papillary muscles from hearts of WKY rats, papillary muscles from hypertrophied hearts of the 18-mo-old SHR exhibited a prolonged time to peak tension, electromechanical delay time, and an increase in resting tension measured at the apex of the length-tension curve. Adenine nucleotide (ATP and ADP) contents of oxygenated papillary muscles were not significantly different between SHR and WKY strains at 6 or 18 mo of age, but CrP content of hearts from adult WKY and SHR were higher than for aged WKY and SHR rats. For up to 30 min of hypoxia (95% N2-5% CO2), muscles from the 18-mo-old SHR and WKY rats demonstrated improved tolerance to hypoxia compared with muscles from younger animals. However, at 60 min of hypoxia the 18-mo-old SHR demonstrated lower active tension and adenylate energy charge [(1/2 ADP + ATP)/(ATP + ADP + AMP)]. At higher glucose concentrations (22 mM), both 18-mo-old WKY and SHR demonstrated improved tolerance to hypoxia; moreover, the differences between strains were no longer evident. Following reoxygenation with 5.5 mM glucose, contracture tension and CrP content recovered to near prehypoxic control levels, whereas developed tension and ATP content remained moderately depressed for all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Vasomotor properties of immature canine coronary collateral circulation
Authors: Hautamaa P. V. , Dai X. Z. , Homans D. C. , Robb J. F. , Bache R. J.
Published: December 2017

This study examined the ability of the immature coronary collateral circulation to undergo vasodilation in response to nitroglycerin and vasoconstriction in response to alpha-adrenoceptor stimulation. Studies were performed in 12 anesthetized dogs. Collateral flow was estimated from measurements of retrograde flow from the acutely ligated and cannulated anterior descending branch of the left coronary artery. Antegrade flow into the collateral-dependent myocardium was minimized by embolizing the anterior descending artery with 25-microns microspheres. Drugs to be tested were introduced into the left main coronary artery to reach collateral vessels arising from the left circumflex and septal arteries. Intracoronary administration of nitroglycerin (6 micrograms X kg-1 X min-1) resulted in a 33 +/- 7.7% increase in retrograde blood flow (P less than 0.01) and a 23 +/- 3.8% decrease in calculated collateral resistance (P less than 0.01). No significant change occurred in retrograde blood flow or calculated collateral resistance during cardiac sympathetic nerve stimulation after beta-adrenergic blockade with propranolol, selective alpha-adrenergic stimulation with phenylephrine (1 microgram X kg-1 X min-1), or selective alpha 2-stimulation with BHT 933 (2 micrograms X kg-1 X min-1). Thus, the immature coronary collateral circulation was capable of active vasomotion, as demonstrated by vasodilation in response to nitroglycerin, but did not undergo vasoconstriction in response to alpha-adrenoceptor stimulation.
Nuclear magnetic resonance studies of intracellular ions in perfused frog heart
Authors: Burstein D. , Fossel E. T.
Published: December 2017

Intracellular sodium, potassium, and lithium were observed in a perfused frog heart by nuclear magnetic resonance (NMR) spectroscopy. A perfusate buffer containing the shift reagent, dysprosium tripolyphosphate, was used in combination with mathematical filtering or presaturation of the extracellular resonance to separate the intra- and extracellular sodium NMR signals. Addition of 10 microM ouabain to the perfusate, perfusion with a zero potassium, low-calcium buffer, and replacement of 66% of the perfusate sodium with lithium resulted in the following percent changes in the intracellular sodium levels (mean +/- SD): ouabain + 460 +/- 60% (n = 6), zero potassium + 300 +/- 30% (n = 3), and lithium - 51 +/- 6% (n = 3). An increase of 45% in the intracellular sodium was observed when changing the pacing rate from 0 to 60 beats/min (with proportional changes for intermediate pacing rates). The ratio of intracellular potassium to sodium concentration was determined to be 2.3 by NMR, indicating that a substantial amount of the intracellular potassium is undetectable with these NMR methods. In addition, intracellular lithium was observed during perfusion with a lithium-containing perfusate.
Role of adrenal catecholamines in cerebrovasodilation evoked from brain stem
Authors: Iadecola C. , Lacombe P. M. , Underwood M. D. , Ishitsuka T. , Reis D. J.
Published: December 2017

We studied whether adrenal medullary catecholamines (CAs) contribute to the metabolically linked increase in regional cerebral blood flow (rCBF) elicited by electrical stimulation of the dorsal medullary reticular formation (DMRF). Rats were anesthetized (alpha-chloralose, 30 mg/kg), paralyzed, and artificially ventilated. The DMRF was electrically stimulated with intermittent trains of pulses through microelectrodes stereotaxically implanted. Blood gases were controlled and, during stimulation, arterial pressure was maintained within the autoregulated range for rCBF. rCBF and blood-brain barrier (BBB) permeability were determined in homogenates of brain regions by using [14C]iodoantipyrine and alpha-aminoisobutyric acid (AIB), respectively, as tracers. Plasma CAs (epinephrine and norepinephrine) were measured radioenzymatically. DMRF stimulation increased rCBF throughout the brain (n = 5; P less than 0.01, analysis of variance) and elevated plasma CAs substantially (n = 4). Acute bilateral adrenalectomy abolished the increase in plasma epinephrine (n = 4), reduced the increases in flow (n = 6) in cerebral cortex (P less than 0.05), and abolished them elsewhere in brain (P greater than 0.05). Comparable effects on rCBF were obtained by selective adrenal demedullation (n = 7) or pretreatment with propranolol (1.5 mg/kg iv) (n = 5). DMRF stimulation did not increase the permeability of the BBB to AIB (n = 5). We conclude that the increases in rCBF elicited from the DMRF has two components, one dependent on, and the other independent of CAs. Since the BBB is impermeable to CAs and DMRF stimulation fails to open the BBB, the results suggest that DMRF stimulation allows, through a mechanism not yet determined, circulating CAs to act on brain and affect brain function.
Hemorrhagic shock impairs myocardial cell volume regulation and membrane integrity in dogs
Authors: Horton J. W.
Published: December 2017

An in vitro myocardial slice technique was used to quantitate alterations in cell volume regulation and membrane integrity after 2 h of hemorrhagic shock. After in vitro incubation in Krebs-Ringer-phosphate medium containing trace [14C]inulin, values (ml H2O/g dry wt) for control nonshocked myocardial slices were 4.03 +/- 0.11 (SE) for total water, 2.16 +/- 0.07 for inulin impermeable space, and 1.76 +/- 0.15 for inulin diffusible space. Shocked myocardial slices showed impaired response to cold incubation (0 degrees C, 60 min). After 2 h of in vivo shock, total tissue water, inulin diffusible space, and inulin impermeable space increased significantly (+19.2 +/- 2.4, +8.1 +/- 1.9, +34.4 +/- 6.1%, respectively) for subendocardium, whereas changes in subepicardium parameters were minimal. Shock-induced cellular swelling was accompanied by an increased total tissue sodium, but no change in tissue potassium. Calcium entry blockade in vivo (lidoflazine, 20 micrograms X kg-1 X min-1 during the last 60 min of shock) significantly reduced subendocardial total tissue water as compared with shock-untreated dogs. In addition, calcium entry blockade reduced shock-induced increases in inulin impermeable space and inulin diffusible space. In vitro myocardial slice studies confirm alterations in subendocardial membrane integrity after 2 h of in vivo hemorrhagic shock. Shock-induced abnormalities in myocardial cell volume regulation are reduced by calcium entry blockade in vivo.
Inducers of adenylate cyclase reverse the effect of leukotriene D4 in isolated working guinea pig heart
Authors: Bjornsson O. G. , Kobayashi K. , Williamson J. R.
Published: December 2017

The recovery of coronary flow and cardiac work was studied in isolated guinea pig hearts (working-heart preparation) after successive bolus injections of leukotriene D4 (LTD4) at increasing doses (0.01-1,000 ng). LTD4 caused an immediate (within 1 min) reduction in coronary flow and cardiac work and an increase in myocardial NADH fluorescence. There was limited spontaneous recovery at any dose and at the end of the cumulative LTD4 study, coronary flow recovered only from 41.4 +/- (SE) 3.5 (n = 10) to 53.5 +/- 4.7% of initial values, and cardiac work recovered from 21.2 +/- 4.1 to 33.1 +/- 5.6% (P less than 0.05). Adenosine (1 X 10(-6) M) or iloprost (1 X 10(-7) M) restored coronary flow but not cardiac work after LTD4 injections, in contrast to full recovery of cardiac work observed in hearts subjected to a similar degree of ischemia induced by reducing the coronary flow by a peristaltic pump, or hypoxia caused by reducing PO2 of the perfusion fluid. Adenosine (1 X 10(-6) M) and forskolin (1 X 10(-6) M) in combination, or iloprost (1 X 10(-7) M) and isoproterenol (1 X 10(-8) M) in combination, restored both coronary flow and cardiac work to control levels. Myocardial NADH levels, which increased immediately after LTD4 injections, returned to normal after perfusion with adenosine or iloprost. The data suggest that LTD4 has a prolonged vasoconstrictive effect on the heart. Reversal of this effect by compounds that stimulate adenylate cyclase of the vascular tissue (adenosine, prostacyclin) revealed a direct suppressive effect on the myocardium independent of the vascular effect and myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Prospective prediction of O2 consumption from pressure-volume area in dog hearts
Authors: Suga H. , Yasumura Y. , Nozawa T. , Futaki S. , Igarashi Y. , Goto Y.
Published: December 2017

Systolic pressure-volume area (PVA) is the area circumscribed by the end-systolic pressure-volume (PV) line, the end-diastolic PV curve, and the systolic PV trajectory of the ventricle. PVA represents the total mechanical energy generated by ventricular contraction. Myocardial O2 consumption (VO2) linearly correlates with PVA under different pre- and afterloads in the dog left ventricle. The linear VO2-PVA relation parallel shifts with changes in contractility index Emax. We have retrospectively obtained VO2 = A X PVA + B . Emax + C, where A, B, and C are regression coefficients. We used this equation to prospectively predict VO2 from measured PVA and Emax in a new group of dog left ventricles. Coefficient of determination (CD) of measured VO2 from predicted VO2 was 0.86 +/- 0.09 (SD) in individual hearts, but decreased to 0.72 when data of the five hearts were pooled. These prospective CDs in individual hearts and all hearts were smaller than retrospective CDs in the individual hearts (0.90 +/- 0.06). Inter-individual variations of A,B, and C caused the lower prospective predictability.
Ventricular electrophysiological properties: is interspecies variability related to thyroid state?
Authors: Binah O. , Arieli R. , Beck R. , Rosen M. R. , Palti Y.
Published: December 2017

Whereas action potential (AP) duration, area, and repolarization vary considerably, ventricular AP characteristics such as resting membrane potential, AP amplitude, and maximal upstroke velocity of phase 0 depolarization appear similar in a variety of mammalian species. As it has been shown that modifications of the thyroid state are associated with alterations in ventricular electrophysiological properties, we hypothesized that some variations in transmembrane potentials among mammalian species result in part from differences in the individual thyroid states. To test this hypothesis, we used standard microelectrode techniques to study ventricular APs in the dog, mole-rat, guinea pig, rat, mouse, and shrew, which encompass a wide range of thyroid states. In these species O2 consumption ranges from 0.38 (in the shrew) to 4.05 ml O2 X g-1 X h-1 (in the dog). We found that resting membrane potential and AP amplitude, duration, and area were inversely correlated with O2 consumption. The correlation coefficients between these parameters with O2 consumption were -0.92, -0.78, -0.91, and -0.92, respectively. We further tested the hypothesis in guinea pigs in which we modified the thyroid state in opposite directions by thyroxine administration and by propylthiouracil treatment. In the hypothyroid myocardium, AP duration (cycle length = 2,000 ms) markedly increased (P less than 0.001), whereas in the hyperthyroid myocardium, resting membrane potential and AP amplitude (P less than 0.01) and duration (P less than 0.001) decreased. We conclude that interspecies variations in ventricular electrophysiological properties can be correlated with the thyroid state, which may be an important determinant of these properties.
Vasopressin facilitates inhibition of renal nerve activity mediated through vagal afferents
Authors: Gupta B. N. , Abboud A. L. , Floras J. S. , Aylward P. E. , Abboud F. M.
Published: December 2017

We measured the effect of vasopressin (8 mU X kg-1 X min-1) on reflex inhibition of renal sympathetic nerve activity induced by volume expansion in 13 sinoaortic-denervated anesthetized rabbits. Volume expansion increased left ventricular end-diastolic pressure (LVEDP) from 5.1 +/- 0.7 to 14.1 +/- 1.4 mmHg and decreased renal nerve activity (RNA) from 57.4 +/- 6.9 to 30.2 +/- 5.6 impulses/s. Infusion of vasopressin elevated LVEDP from 6.0 +/- 1.0 to 7.3 +/- 1.1 mmHg and decreased RNA from 61.8 +/- 7.2 to 47.1 +/- 6.3 impulses/s. Heart rate fell from 243 +/- 7 to 231 +/- 9 beats/min; no other significant hemodynamic changes were seen. During the infusion of vasopressin, volume expansion increased LVEDP to 13.7 +/- 1.2 mmHg and decreased RNA to 17.0 +/- 4.2 impulses/s. The slopes relating the percent decrease in RNA to the rise in LVEDP were calculated from values of RNA recorded at several levels of LVEDP. The slope averaged -6.2 +/- 1.1%/mmHg before vasopressin and nearly doubled (-11.9 +/- 1.8%/mmHg) during vasopressin. Infusion of placebo (saline) instead of vasopressin did not alter the reflex inhibition of nerve activity. Bilateral vagotomy abolished the decrease in resting nerve activity that occurred during infusion of vasopressin as well as the reflex inhibition of RNA. These data demonstrate that vasopressin facilitates the reflex inhibition of renal sympathetic nerve activity associated with increases in LVEDP and mediated through vagal afferents.
Effects of reducing [Na+]o on catecholamine-induced delayed afterdepolarizations in atrial cells
Authors: Tseng G. N. , Wit A. L.
Published: December 2017

Atrial cells of the canine coronary sinus generate arrhythmogenic delayed afterdepolarizations (DADs) in the presence of catecholamines. We studied the direct effects of reducing extracellular Na+ concentration ([Na+]o) to determine whether it is an important charge carrier of the DADs. We also compared the effects of sucrose substitution and Li+ substitution to obtain some insight into the ionic mechanism mediating the DADs, because Li+ can substitute for Na+ in various Na+ channels but not in electrogenic Na+-Ca2+ exchange. Reducing [Na+]o for 2–5 min caused complicated changes in electrical and mechanical properties of coronary sinus cells. When Li+ was used as a substitute, there was initially a decrease in the DAD within 25 s. Action potential duration decreased, resting tension increased, and twitch tension decreased. After 85 s, a small delayed afterdepolarization reappeared, membrane potential depolarized, and the aftercontraction increased. When sucrose was used as a substitute similar changes occurred except membrane potential hyperpolarized. Some of these changes suggest an elevation in intracellular [Ca2+] and subsequent alterations in membrane properties. To distinguish the direct effect of reducing [Na+]o from these indirect effects, we used a fast-flow superfusion system and thin, small preparations (approximately 1 mm wide, 4 mm long, and 6-12 cell layers thick). Under such conditions, 2- to 3-s solution changes could modify extracellular [Na+] without significantly affecting intracellular ionic composition. Brief periods of [Na+]o reduction during the DAD caused a decrease in its amplitude and rate of depolarization when either sucrose or Li+ was used as a substitute for Na+, without the other changes in membrane potential which occur during prolonged [Na+]o reduction. These results suggest Na+ is an important charge carrier for the inward current causing DADs in coronary sinus cells, and the membrane system mediating DADs may be either electrogenic Na+-Ca2+ exchange or a combination of electrogenic Na+-Ca2+ exchange and some other mechanism such as cation channels permeable to Li+.
Peripheral circulatory control of preload-afterload mismatch with angiotensin in dogs
Authors: Lee R. W. , Lancaster L. D. , Buckley D. , Goldman S.
Published: December 2017

To determine whether changes in the venous circulation were responsible for preload-afterload mismatch with angiotensin, we examined the changes in the heart and the peripheral circulation in six splenectomized dogs after ganglion blockade during an angiotensin infusion to increase mean aortic pressure 25 and then 50%. The peripheral circulation was evaluated by measuring mean circulatory filling pressure (MCFP), arterial compliance, and venous compliance. A 25% increase in mean aortic pressure increased MCFP from 6.2 +/- 0.3 to 7.6 +/- 0.3 mmHg (P less than 0.001) but did not change cardiac output, heart rate, or stroke volume. Systemic vascular resistance increased (P less than 0.01) from 0.50 +/- 0.02 to 0.59 +/- 0.03 mmHg X min X kg X ml-1. Arterial and venous compliances decreased (P less than 0.01) from 0.08 +/- 0.03 to 0.06 +/- 0.03 ml X mmHg-1 X kg-1 and from 2.1 +/- 0.1 to 1.6 +/- 0.1 ml X mmHg-1 X kg-1, respectively. A 50% elevation in mean aortic pressure increased MCFP from 7.1 +/- 0.4 to 9.5 +/- 0.9 mmHg (P less than 0.001) but did not change heart rate. At this level of aortic pressure, cardiac output and stroke volume decreased (P less than 0.01) 12 and 19%, respectively, whereas systemic vascular resistance increased (P less than 0.001) from 0.48 +/- 0.03 to 0.83 +/- 0.05 mmHg X min X kg X ml-1. Arterial and venous compliances decreased (P less than 0.01) from 0.08 +/- 0.01 to 0.05 +/- 0.01 ml X mmHg-1 X kg-1 and from 2.1 +/- 0.1 to 1.4 +/- 0.1 ml X mmHg-1 X kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Conduction blocks in and around preferential pathway of dog right atrium
Authors: Yamashita K. , Hiraoka M. , Adaniya H.
Published: December 2017

We studied conduction properties and histological findings at branching sites of the pectinate muscle (PM) from the crista terminalis (CT) in the dog right atrium. Propagation was faster in the longitudinal direction along CT than along PM. When the rate of stimulation was increased, conduction blocks to PM occurred at a longer cycle length than those to CT in 10 of 19 cases without differences in the refractory period. There were two block sites, one at the lateral edge within CT and the other at the branching site of PM from CT. The former was dominant with normal solution and the latter with high K+ solution. Histological studies showed no apparent differences between the two groups. CT consisted of a number of unit bundles in a longitudinal direction. The unit bundles continuing from the edge of CT proceeded into PM. Their orientation in PM, however, became irregular and tangled. Between the branches of PM, conduction block occurred unpredictably without regard to direction. These observations indicated the importance of the arrangement and orientation of the unit bundles in the appearance of the preferential conduction and block.
Integral-mass balance method for determination of solvent drag reflection coefficient
Authors: Wolf M. B. , Watson P. D. , Scott D. R.
Published: December 2017

We have developed the integral-mass balance (IMB) method to measure the solvent drag reflection coefficient (sigma f) for transcapillary macromolecular transport in skeletal muscle and other organs. Of course, sigma f is calculated from the cumulative amounts of water and macromolecule that move convectively across the microvascular membrane as determined from changes in hematocrit and plasma macromolecule concentration over a period of fluid filtration. We have investigated the effects of both theoretical and experimental factors that affect the validity and accuracy of the method. The effect of the following factors on sigma f determination by the IMB method were explored: low Peclet number; random-measurement errors; and systematic errors due to vascular leakage, hemolysis of red blood cells, evaporation, and osmolality changes. We found that all of these factors produced overestimations of sigma f, but their effects could be corrected. Also, appropriate experimental design could minimize these effects. Experiments using the IMB method in the isolated, perfused cat hindlimb preparation to determine sigma f for albumin and plasma proteins resulted in mean values of 0.82 +/- 0.08 (SD) (n = 7) and 0.83 +/- 0.02 (n = 4), respectively.
Effect of phorbol esters on contractile state and calcium flux in cultured chick heart cells
Authors: Leatherman G. F. , Kim D. , Smith T. W.
Published: December 2017

Phorbol esters are potent tumor promoters that have been widely used in studies of transmembrane signaling because of their ability to activate protein kinase C. To study the effect of phorbol esters (and indirectly, the role of protein kinase C) on cardiac muscle contractility, we examined the effects of phorbol myristate acetate (PMA) on contractile state, transmembrane 45Ca fluxes, and cytosolic free Ca concentration ([Ca]i) using spontaneously contracting cultured chick ventricular cells. PMA produced a concentration- and time-dependent decrease in the amplitude of cell motion [half maximum inhibitory concentration (IC50) = 130 nM] with maximal effect (54 +/- 5% of control) observed at 1 microM. PMA (1 microM) reduced 45Ca uptake rate by 16 +/- 4% (P less than 0.05) and the size of the rapidly exchangeable Ca pool by 11 +/- 2% (P less than 0.05) but did not alter the 45Ca efflux rate. In fura-2-loaded cells, PMA produced a decrease in [Ca]i from 96 +/- 7 to 72 +/- 5 nM (mean +/- SE; P less than 0.05) with a time course similar to that of alteration in contractile amplitude. PMA had no effect on cellular Na content. Phorbol didecanoate (1 microM), a phorbol diester that does not activate protein kinase C, produced no significant changes in contractile amplitude, 45Ca fluxes, or [Ca]i. These results indicate that PMA influences transsarcolemmal Ca uptake, and thus the excitation-contraction process, and suggest that protein kinase C may modulate myocardial Ca homeostasis and contractile state.
Stimulation of myocardial coenzyme A degradation by fatty acids
Authors: Lopaschuk G. D. , Neely J. R.
Published: December 2017

Coenzyme A (CoA) levels were increased in isolated hearts from 537 +/- 14 to 818 +/- 44 nmol/g dry wt by perfusion for 45 min under conditions known to stimulate CoA synthesis (5). Subsequently, perfusion of these hearts with buffer containing glucose (11 mM) and pyruvate (5 mM) for 3 min had no effect on CoA levels (789 +/- 42 nmol/g dry wt). However, perfusion with a buffer containing glucose (11 mM) and palmitate (1.2 mM) decreased CoA levels to 683 +/- 34 nmol/g dry wt within 3 min. This decrease in CoA appeared to occur in the cytosolic compartment with no change in mitochondrial CoA content and was associated with a rise in tissue content of long-chain acyl-CoA. An increased incorporation of fatty acids into triglycerides was associated with the rise in total acyl-CoA suggesting that long-chain acyl-CoA levels were elevated in the cytosolic compartment. Perfusion conditions which maximally increased acyl-CoA levels also maximally stimulated CoA degradation. These observations suggest that the cytosolic degradation of CoA is related to high levels of long-chain acyl-CoA in this compartment. Use of these perfusion conditions in future studies should help define the pathway of CoA degradation and determine the mechanisms which control cellular levels of CoA.
Nonuniformity of CBF response to NE- or ANG II-induced hypertension in rabbits
Authors: Reynier-Rebuffel A. M. , Aubineau P. , Issertial O. , Seylaz J.
Published: December 2017

The regional response of brain vasculature to moderate hypertension was investigated using two hypertensive drugs, norepinephrine (NE) and angiotensin II (ANG II), infused intravenously at low concentrations (increase in blood pressure 15–40 mm Hg). Regional cerebral blood flow (rCBF) was measured in unanesthetized and anesthetized rabbits using the [14C]ethanol saturation technique. In both groups of animals, NE and ANG II induced regional differences in the flow changes as compared with controls, confirming a regional (or segmental) heterogeneity in the regulatory mechanisms to hypertension. The responses to identical rises in blood pressure (BP) in most of the structures analyzed depended on the drug used. In the unanesthetized rabbits, the increase in vascular resistance induced by NE was greater than that induced by ANG II. With the two drugs, there was no correlation between the flow changes in any of the structures considered and either the BP increase or the BP level in unanesthetized animals. However, these flow changes were correlated with the BP increase in anesthetized animals, although differences between the effects of NE and ANG II were again observed. This study suggests that cerebrovascular regulatory mechanisms in hypertension are probably more complex than a simple myogenic reaction. Their heterogeneity and their dependence both on the cause of hypertension and on the presence of anesthetics suggest the intervention of an integrating pathway.
Altered cardiac polyamine biosynthesis in spontaneously hypertensive rats
Authors: Ruskoaho H. , Raunio H.
Published: December 2017

To evaluate the role of polyamine biosynthesis in myocardial growth, the activity of ornithine decarboxylase (ODC) and the levels of the polyamines, spermidine, spermine, and putrescine, were measured in the hearts of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats between birth and 30 wk of age and in 30-wk-old rats after 6 wk treatment with either minoxidil (0.08 mg/ml) or methyldopa (5 mg/ml drinking water). ODC activity was initially high in the developing heart (150 pmol X mg protein-1 X 30 min-1) and decreased with age. In the SHR after 4 wk of age, spermidine content was consistently raised in both ventricles compared with the WKY rats. Spermine was reduced in the left ventricle of the SHR, resulting in high spermidine-to-spermine ratios characteristic of rapidly growing systems. Ventricular ODC activity and putrescine levels were also slightly but less consistently elevated in the ventricles of the SHR compared with respective WKY rats. Minoxidil treatment increased heart weight and left ventricular spermidine and spermine content in both SHR and WKY rats. Methyldopa also caused a significant increase in left ventricular spermidine content despite a marked reduction in ventricular mass. Thus ventricular hypertrophy in SHR is accompanied by an enhanced synthesis and accumulation of spermidine. The fact that myocardial spermidine content increased during methyldopa treatment, which reduced the myocardial mass, suggests that regression of ventricular hypertrophy can occur independently of changes in polyamine content.
Volume-pressure relationship (compliance) of interstitium in dog skin and muscle
Authors: Wiig H. , Reed R. K.
Published: December 2017

The relationship between changes in interstitial fluid volume (IFV) and pressure (IFP) during over- and dehydration was estimated in hindlimb skin and skeletal muscle of 17 dogs. IFV was measured as the extravascular distribution volume of 51Cr-EDTA after nephrectomy and IFP with micropipettes, wick-in-needle technique (WIN), and perforated capsules. Control IFP (micropipettes) averaged -1.7 +/- 0.5 (n = 17) and 0.0 +/- 1.0 mmHg (SD; n = 17) in skin and muscle, respectively, not different from corresponding WIN and capsule pressures in subcutis. Control IFV was 0.93 +/- 0.34 (n = 17) and 0.42 +/- 0.11 ml/g dry wt (SD; n = 17) in skin and muscle, respectively. Peritoneal dialysis with 20% glucose reduced IFV by 27% in skin and by 44% in muscle, whereas micropipette IFP fell gradually by approximately 4 mmHg in skin and muscle. Compliance during dehydration was 7.6 and 12.5% change in IFV per millimeter Hg fall in IFP (micropipettes) in skin and muscle, respectively, whereas compliance in subcutis based on perforated capsule pressure was 2.0% change in IFV per millimeter Hg. The maximal increase in IFP during overhydration was approximately 2 mmHg in both skin and muscle. Skin and muscle compliance in dogs did not differ significantly from that of rats and cats. We conclude that the difference in compliance among previous studies mainly results from different methods for IFP measurement but is probably also influenced by the state of hydration before altering IFV.
Coronary input impedance during cardiac cycle as determined by impulse response method
Authors: Van Huis G. A. , Sipkema P. , Westerhof N.
Published: December 2017

The coronary arterial system was characterized by its input impedance determined in systole and diastole from impulse response functions in five dogs. The impulse response technique was verified on a known hydraulic system. A second confirmation was obtained on the circumflex artery: reflected pulses were correlated with site of reflections generated by occlusions. The impulse response indicates discrete reflections, superimposed on the tail of the response, resulting from diffuse reflections. Input impedance was calculated from Fourier analysis of the impulse response. Characteristic impedance was 1.0 +/- 0.2 X 10(9) Pa X s X m-3 (0.13 +/- 0.02 mmHg X ml-1 X min) and impedance at 0 Hz was 2.6 +/- 0.8 X 10(9) Pa X s X m-3. No significant differences between systole and diastole were found in both characteristic impedance and impedance at 0 Hz. It is concluded that the coronary system consists of a proximal part that can be described with the three-element windkessel and a distal part not seen by oscillatory pressure or flow perturbations, which depends on the phase of cardiac contraction.
Effects of L-thyroxine in rats with chronic heart failure after myocardial infarction
Authors: Gay R. , Gustafson T. A. , Goldman S. , Morkin E.
Published: December 2017

The effects of thyroid hormone on left ventricular (LV) function and myosin isoenzyme distribution were evaluated in rats 3 wk after myocardial infarction. When compared with normal rats, animals selected for study had moderately severe LV dysfunction as judged by decreased aortic and LV systolic pressures and a 34% decrease in LV maximum rate of pressure development (dP/dt). Average LV end-diastolic pressure was increased to 26 +/- 1 mmHg from 5 +/- 1 mmHg. The infarcted rats were divided into saline-treated control (n = 10) and treatment (n = 13) groups. The latter group received thyroxine (T4, 1.5 micrograms/100 g body wt) immediately after the first determination of pressures and at 24 and 48 h. At 72 h, aortic and LV pressures and myosin isoenzyme composition were measured. In the thyroxine-treated group LV end-diastolic pressure decreased from 27 +/- 2 to 18 +/- 2 mmHg, and LV dP/dt increased from 5,627 +/- 249 to 6,064 +/- 355 mmHg/s. Heart rate and aortic pressure did not change. After saline injections, LV end-diastolic pressure remained elevated, and the other hemodynamic parameters were unchanged. Determination of ventricular myosin isoenzyme composition in the saline-treated group revealed an increase in the V3 myosin isoform and a decrease in the V1 isoform as compared with the normal values. This pattern was not altered by T4 treatment. A separate group (n = 7) of rats was treated with a 10 times larger dose of thyroxine (15 micrograms/100 g body wt) for the same period of time. In this group, there was neither hemodynamic improvement nor changes in myosin isoenzyme distribution.(ABSTRACT TRUNCATED AT 250 WORDS)
Tunneling cell processes in myocytes of stretched mouse atria
Authors: Page E. , Goings G. E. , Power B. , Upshaw-Earley J.
Published: December 2017

Serial section electron micrographs of mouse atria stretched in vitro show that myocytes have cell processes which tunnel into adjacent myocytes for 8 microns or more. The tunneling cell processes (TCP) (diam 4–6.2 microns) lack myofibrils and organelles associated with atrial peptide secretion. The glycogen-rich TCP cytoplasmic matrix contains conspicuous tubules and vesicles originating from endoplasmic reticulum and resembling free sarcoplasmic reticulum (SR). TCP are surrounded by a plasmalemma derived from their myocyte of origin, the plasmalemma of the tunneled myocyte, and an intervening narrow compartment continuous with the interstitial space. Profiles having the characteristics cytoplasmic structure of TCP are also found both in the interstitial space between myocytes and near the longitudinal terminations where myocyte ends about on the interstitial space. We suggest that TCP tubules and vesicles may proliferate and/or transport in response to stretch, might be free SR, and may respond to stretch-activated changes in ionic composition or potential of the surrounding myocyte and narrow intercellular compartment.
Microlesion formation in myocardial cells by high-intensity electric field stimulation
Authors: Jones J. L. , Jones R. E. , Balasky G.
Published: December 2017

Arrhythmias, S-T segment changes, immediate refibrillation, and other signs of dysfunction are often observed after clinical and experimental transthoracic defibrillation. In vitro studies suggested that shock-induced dysfunction is induced by sarcolemmal dielectric breakdown accompanied by ionic exchanges through transient, shock-induced microlesions in the sarcolemma. To test this hypothesis, cultured chick embryo myocardial cells were shocked in media containing fluorescein isothiocyanate-labeled dextrans (FITC-dextrans) ranging in molecular mass from 4 to 70 kDa, using electric field stimulation 5 ms in duration and ranging in intensity from 0 to 200 V/cm. Results showed that the percentage of cells incorporating 4- to 20-kDa dextrans increased in a dose-dependent manner. The 4- and 10-kDa dextrans were incorporated beginning at intensities of 50–100 V/cm. Dextran incorporation corresponded with shock intensities which produced a shock-induced arrest of spontaneous contraction lasting 1 min. The 20-kDa dextrans were incorporated following 150- and 200-V/cm shocks. Shocks of these intensities also produced a transient postshock contracture. Larger dextrans (40 and 70 kDa) were not incorporated. These results suggest the formation of transient sarcolemmal microlesions having a diameter of 45-60 A during high-intensity electric field stimulation.
Frequency-dependent myocardial depression induced by verapamil in conscious dogs
Authors: Applegate R. J. , Walsh R. A. , O'Rourke R. A.
Published: December 2017

To determine the effects of calcium entry-blocking drugs on the frequency-dependent rate of peak positive left ventricular pressure development [(+)dP/dtmax] we evaluated the effects of incremental left atrial pacing during verapamil, diltiazem, and nifedipine under equivalent loading conditions in seven conscious preinstrumented mongrel dogs. To eliminate the effects of reflex sympathetic stimulation the animals were pretreated with propranolol (2 mg/kg). Prior to atrial pacing (+)dP/dtmax was similar for verapamil [2,392 +/- 416 (SD) mmHg/s], diltiazem (2,661 +/- 606 mmHg/s), and nifedipine (2,731 +/- 636 mmHg/s), P = NS among drugs. At a common peak paced heart rate (150 beats/min) under equivalent loading conditions, (+)dP/dtmax was significantly reduced from the corresponding preatrial pacing value only after verapamil (2,131 +/- 415 mmHg/s, P less than 0.03) and was significantly lower than after either diltiazem (2,547 +/- 550 mmHg/s) or nifedipine (2,633 +/- 705 mmHg/s, P less than 0.04). No significant linear relation was observed between stimulation frequency and (+)dP/dtmax during atrial pacing alone (slope = -2.2 +/- 1.3, r = -0.30 +/- 0.23, P = 0.12), during atrial pacing with beta-blockade alone (slope = 1.7 +/- 1.5, r = 0.24 +/- 0.25, P = 0.25), or beta-blockade combined with diltiazem (slope = -0.91 +/- 1.3, r = 0.02 +/- 0.23, P = 0.38) or nifedipine (slope = -1.2 +/- 1.3, r = 0.01 +/- 0.23, P = 0.48). By contrast, a significant negative force-frequency relation was seen during incremental atrial pacing after verapamil (slope = -4.1 +/- 1.3, r = -0.80 +/- 0.23, P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic effects on internal cardiac defibrillation threshold
Authors: Rattes M. F. , Sharma A. D. , Klein G. J. , Szabo T. , Jones D. L.
Published: December 2017

Autonomic neural tone modulates arrhythmias and could affect the efficacy of an implantable defibrillator if defibrillation threshold is also altered by changes in neural activity. We determined the effects of alpha- and beta-adrenoceptor agonists and antagonists on the energy requirement for defibrillation using a sequential-pulse technique in anesthetized pigs. The doses for each drug were selected based on the results of dose-response curves. The mean defibrillation threshold was 10.2 +/- 0.65 J (mean +/- SE) in control and 10.0 +/- 0.84, 9.4 +/- 0.87 and 8.9 +/- 0.89 J during phenylephrine infusions of 0.7, 1.35, and 2.0-4.0 micrograms X kg-1 X min-1 [n = 8, P = not significant (NS)]. Phenylephrine at all infusion rates increased the ventricular fibrillation threshold, indicating that effects on the ventricular fibrillation threshold may occur independent of changes in defibrillation threshold. No significant change was observed in the defibrillation threshold before and after administration of isoproterenol (6.5 +/- 0.72 and 6.7 +/- 0.93 J, n = 8, P = NS). Similarly, no change in defibrillation thresholds was observed after 1.5-2.0 mg/kg phentolamine (8.5 +/- 0.85 and 7.9 +/- 0.93 J, n = 8, P = NS) or 3.0-6.0 mg/kg atenolol (10.0 +/- 1.7 and 10.3 +/- 2.6 J, n = 8, P = NS). However, when defibrillation threshold was determined using a single-pulse method, isoproterenol infusion produced a significant decrease (17.3 +/- 1.5 vs. 14.6 +/- 1.9 J, n = 7, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)