bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial metabolic inhibition and membrane potential, contraction, and potassium uptake
Authors: Hasin Y. , Barry W. H.
Published: December 2017

Interruption of synthesis of ATP during hypoxia or ischemia can produce membrane depolarization that may be related to inhibition of Na+-K+-ATPase. To examine this hypothesis, the effects of exposure of cultured chick embryo ventricular cells to 1 mM cyanide (CN), to 20 mM 2-deoxy-D-glucose (2-DG), to CN + 2-DG, and to ouabain (10(-3) M) on contraction, membrane potential, and 42K uptake were determined. CN produced moderate membrane depolarization and electromechanical uncoupling within 2 min. 2-DG caused marked membrane depolarization with a transient negative inotropic effect. Exposure to CN + 2-DG produced marked depolarization (-38 mV) and mechanical arrest of the cells in a relaxed state. Ouabain produced marked depolarization (-39 mV) and contracture of the cells. Uptake of 42K was inhibited by 10(-3) M ouabain within seconds. However, CN + 2-DG produced no inhibition of 42K uptake within the first 2 min of exposure, and inhibition of the Na pump by CN + 2-DG required 30 min to develop fully. Exposure to CN alone produced no inhibition of 42K uptake, whereas moderate inhibition was produced by 2-DG alone even when substrate for oxidative phosphorylation was provided. We conclude that the acute effects of inhibition of glycolysis and oxidative phosphorylation on membrane potential and contraction in these cells are not due to inhibition of the Na pump and that during partial metabolic inhibition active univalent cation transport in these cells is relatively dependent on ATP derived from glycolysis, whereas contraction is more dependent on ATP supplied by oxidative phosphorylation.
Effect of beta-adrenergic blockade on nucleoside release from the hypoperfused isolated heart
Authors: Wangler R. D. , DeWitt D. F. , Sparks H. V.
Published: December 2017

Myocardial ischemia increases the release of adenosine (RADO), inosine (RINO), and norepinephrine; however, it is not known whether norepinephrine contributes to nucleoside production via the beta-adrenergic receptor. We used a Langendorff preparation (guinea pig) to study the time course of RADO and RINO during myocardial hypoperfusion (MH) produced by decreasing perfusion pressure from 60 to 30 cmH2O. Data are expressed as means +/- SE. RADO and RINO significantly increased from 21 +/- 2 and 418 +/- 89 pmol X min-1 X g-1 to 206 +/- 26 and 2,401 +/- 598, respectively, by 10 min of MH. By 20 min, RADO and RINO had decreased significantly to 111 +/- 15 and 912 +/- 169 pmol X min-1 X g-1. RADO remained at that level for the remaining 160 min, whereas RINO returned to the control level. Coronary flow and myocardial O2 consumption were constant during MH. In the presence of 10(-7) M dl-propranolol MH did not produce the initial peak RADO; RADO increased to 95 +/- 18 pmol X min-1 X g-1 at 10 min and then did not change. Also, the initial peak RINO was significantly reduced (687 +/- 67 pmol X min-1 X g-1 at 10 min). Similar results were obtained with atenolol (5 X 10(-6) M), a beta-receptor antagonist without membrane-stabilizing effects. In the presence of 10(-5) M dl-propranolol, MH did not increase nucleoside release above control. Nucleoside release was similarly blocked during MH in the presence of 5 X 10(-6) M d-propranolol, which does not have the beta-blocking properties of the l-isomer.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of adenosine receptor agonists in the isolated, perfused rat kidney
Authors: Murray R. D. , Churchill P. C.
Published: December 2017

Two subclasses of adenosine receptors, A1 and A2, have been described. The purpose of these experiments was to determine and compare the renal effects of several adenosine receptor agonists: adenosine (Ado), 2-chloroadenosine (2CA, nonselective), N6-cyclohexyladenosine (CHA, A1 selective), and N6-ethylcarboxamide adenosine (NECA, A2 selective). Rat kidneys were perfused at constant pressure (105 +/- 5 mmHg) using a Krebs-Henseleit buffer containing 3.5 g/100 ml Ficoll and 1.0 g/100 ml bovine serum albumin. Three clearance periods were obtained in each kidney, i.e., control, experimental [drug at 1 microM or vehicle (NaCl)], and recovery. Perfusate flow was increased by Ado, 2CA, and NECA but not affected by CHA. Glomerular filtration was increased by NECA, decreased by CHA, and not affected by Ado and 2CA. Afferent arteriolar resistance was decreased by NECA, increased by CHA, and unaffected by Ado and 2CA. Efferent arteriolar resistance was decreased by all agonists. CHA tended to decrease renin secretion whereas NECA significantly increased it. The results suggest that the renal vasculature possesses both A1 and A2 adenosine receptors and that activation of A2 receptors mediates arteriolar dilation and stimulation of renin secretion whereas activation of A1 receptors mediates arteriolar constriction and possibly inhibition of renin secretion.
Central nervous system action of angiotensin during onset of renal hypertension in awake rats
Authors: Faber J. E. , Brody M. J.
Published: December 2017

The increase in arterial pressure and vascular resistance during acute unilateral renal artery stenosis (RSt) in conscious rats is, in part, dependent on elevated neurogenic vascular tone produced by an indirect neural interaction of angiotensin II (ANG II) with the sympathetic nervous system. The present experiments examined whether this interaction occurs within the central nervous system. Conscious rats that had been chronically instrumented with miniaturized Doppler flow probes for measurement of regional vascular resistance were subjected to a 50% reduction in unilateral renal flow with an implanted pneumatic occluder. Arterial pressure increased by 35% after 60 min of RSt. In animals in which the pressor response to intracerebroventricular (icv) ANG II had been eliminated by prior surgical interruption of the "ANG II pressor pathway" in the anterior hypothalamus, the increase in blood pressure following RSt was attenuated by 44% (P less than 0.01). In a second series, a central action of ANG II during acute renal hypertension (RH) was assessed by central ANG II receptor blockade with icv saralasin. Unlike normotensive controls, acutely RH animals responded to saralasin with significant (P less than 0.01) decreases in arterial pressure (-32%) and hindquarters (-26%) and contralateral renal (-9%) resistance. These changes were accentuated (-57% decrease in pressure) in animals made areflexic by prior sinoaortic baroreceptor denervation. Thus activation of the sympathetic nervous system during the early high-renin phase of RH depends significantly on a central action of ANG II. This mechanism may account for some 40-50% of the pressure increase following acute RSt.
Endothelium and asymmetrical responses of the coronary arterial wall
Authors: Cohen R. A. , Shepherd J. T. , Vanhoutte P. M.
Published: December 2017

Changes in isometric tension due to intra- or extraluminal addition of vasoactive agents were determined in isolated perfused segments of canine left circumflex coronary artery. Segments denuded of endothelium were more sensitive to the contractile action of 5-hydroxytryptamine and potassium during intraluminal addition. In segments with intact endothelium, the sensitivity to intraluminal, but not extraluminal, 5-hydroxytryptamine was decreased in comparison to denuded segments; that to potassium was unchanged. In segments with intact endothelium contracted with prostaglandin F2 alpha, intraluminal, but not extraluminal, acetylcholine, adenosine diphosphate, or thrombin caused relaxation. Intraluminal 5-hydroxytryptamine and aggregating platelets caused relaxation or attenuated contractions in a majority of vessels studied; extraluminal addition caused only contractions. Thus the endothelium is responsible for opposite smooth muscle responses to intra- versus extraluminal vasoactive substances released from aggregating platelets. During intraluminal thrombosis the endothelium may inhibit smooth muscle contraction by responding to 5-hydroxytryptamine and adenosine diphosphate released from platelets and to thrombin; where the endothelium is damaged, the luminal aspect of the blood vessel wall, which is more sensitive to 5-hydroxytryptamine, may become the site of coronary spasm.
Neurohormonal characteristics of cardiovascular response due to intraventricular hypertonic NaCl
Authors: Kawano Y. , Ferrario C. M.
Published: December 2017

In morphine-pentobarbital anesthetized dogs (n = 25) we measured the effect of cerebroventricular administration of hypertonic sodium chloride (NaCl) on mean arterial pressure (MAP), heart rate (HR), and integrated renal nerve activity (RNA); in separate experiments (n = 9) we also evaluated the effect of hypertonic NaCl on the osmolarity and electrolyte and catecholamine concentrations of both the blood and the cerebrospinal fluid (CSF); plasma arginine vasopressin (AVP), cortisol, and renin activity were also measured. The intraventricular (ivt) injection of 1.5 M NaCl caused a hypertensive response associated with tachycardia and a significant decrease in RNA (P less than 0.001). Intravenous hexamethonium chloride prevented the changes in HR and RNA, whereas the increases in MAP were markedly reduced but not abolished. The neurohormonal effects of ivt hypertonic NaCl consisted of activation of the sympathoadrenal pituitary axis as reflected by significant increases in the plasma levels of norepinephrine (NE), epinephrine, AVP, and cortisol. On the other hand, there was a significant decrease in plasma renin activity not associated with any significant changes in plasma osmolarity and serum electrolytes. These hormonal changes coincided with an increase in the concentration of CSF NE, CSF Na+, and CSF osmolarity obtained from the cisterna magna. Altogether the results indicate that central administration of hypertonic NaCl in dogs with intact baroreflexes causes a preferential activation of the sympathetic nervous system to vascular systems other than those of the kidneys. In addition, a part of the pressor response may be due to the activation of nonneurogenic mechanisms.
Automaticity of ventricular fibers induced by low concentrations of barium
Authors: Malecot C. , Coraboeuf E. , Coulombe A.
Published: December 2017

The effects of low concentrations of Ba have been studied on dog Purkinje fibers and on guinea pig left ventricular epicardium. In both tissues, Ba induces diastolic depolarization at a membrane potential more negative than -80 mV. This effect becomes clearly detectable at concentrations as low as 10-20 microM in Purkinje fibers bathed in 5.4 mM K Tyrode solution and around 100 microM in ventricular epicardium. In both tissues the Ba-induced depolarization is blocked in a dose-dependent manner by low concentrations of Cs (0.5-5 mM) as is the normal pacemaker current (if) in Purkinje fibers. In ventricular muscle the Ba-induced depolarization develops at the same rate whether the tissue is at rest or depolarized by repetitive stimulation. The maximum (initial) slope of diastolic depolarization is insensitive to D 600, La, and 4-aminopyridine, increased by tetraethylammonium chloride, decreased by tetrodotoxin, and almost entirely suppressed by Na removal. Experimental data and reconstruction of electrical activity suggest that in ventricular muscle the Ba-induced diastolic depolarization results to a large extent from the unmasking of a small pacemaker inward current, mainly carried by Na ions and similar to the pacemaker current of Purkinje fibers. Unmasking of the depolarizing effect of the pacemaker current is very likely due to the decrease by Ba of the inward going rectification. Steady-state inward Na current flowing through the Na window can increase the diastolic depolarization. Residual Cs-insensitive, Ba-induced diastolic depolarization may result from a time-dependent blockade of the background K conductance like the one described in skeletal muscle.
Effects of metabolized and unmetabolized arachidonate on rat platelet shape change
Authors: Lampugnani M. G. , de Gaetano G.
Published: December 2017

Arachidonate (0.12-1.5 mM) initiated a concentration-dependent, saturable shape change of rat platelets suspended in citrated plasma. Interaction of arachidonate with platelets led to the formation of active metabolites that appeared to be the actual inducers of shape change. Among these, prostaglandin endoperoxides rather than thromboxane A2 seemed necessary for shape change. No role of the products of the lipoxygenase pathway could be shown. In the presence of cyclooxygenase and lipoxygenase inhibitors, arachidonate (0.25-0.5 mM) prevented platelet shape change induced by the endoperoxide analog U-46619 but not by other agonists such as ADP or serotonin. Arachidonate acts therefore as both an agonist and an antagonist of platelet shape change. The agonistic effect requires arachidonate metabolism while the antagonistic activity seems to be linked to the fatty acid molecule itself.
Chemically induced cardiovascular reflexes arising from the stomach of the cat
Authors: Longhurst J. C. , Stebbins C. L. , Ordway G. A.
Published: December 2017

We examined the potential for cardiovascular reflexes caused by the application of either bradykinin or capsaicin to the serosal or mucosal surface of the stomach. After application to the serosa, bradykinin (10 micrograms/ml) evoked increases in mean arterial pressure of 12 +/- 2 mmHg, heart rate of 5 +/- 1 beats/min, left ventricular dP/dt (at 40 mmHg developed pressure) of 305 +/- 54 mmHg/s and systemic vascular resistance of 0.04 +/- 0.01 PRU. Capsaicin (200 microgram/ml) caused similar cardiovascular responses. There were no cardiovascular responses when either substance was applied to the gastric mucosa. The responses to both chemicals were abolished by celiac ganglionectomy but not by bilateral vagotomy. To determine whether the cardiovascular responses evoked by bradykinin were caused by smooth muscle contraction, we compared the increases in gastric smooth muscle tension and blood pressure elicited by bradykinin, bethanechol, or acetylcholine. Bethanechol and acetylcholine caused greater increases in tension than bradykinin, whereas bradykinin evoked greater increases in blood pressure than either bethanechol or acetylcholine. We conclude that stimulation of gastric afferents by capsaicin or bradykinin causes cardiovascular reflexes, primarily through activation of chemosensitive receptors.
Unidirectional block between Purkinje and ventricular layers of papillary muscles
Authors: Overholt E. D. , Joyner R. W. , Veenstra R. D. , Rawling D. , Wiedmann R.
Published: December 2017

Previous work has characterized the Purkinje-ventricular junction (PVJ) of papillary muscles as a region of low safety factor with some delay between P and V activation. We have previously shown that the P strand action potential activates a layer of P cells over most of the papillary muscle surface, but activation of the underlying V cells occurs only at specific junctional sites, generally near the base of the muscle. Our present results from both dog and rabbit left papillary muscles show that the junctional regions for propagation from the V layer up into the P layer include not only these specific P-to-V sites but also other sites located more toward the apex of the muscle. These results show that the papillary muscles have regions of potential unidirectional block, although the manifestation of unidirectional block at these sites requires the premature excitation of the ventricular layer.
Effects of 15-hydroperoxy-eicosatetraenoic acid (15-HPETE) on cerebral arterioles of cats
Authors: Christman C. W. , Wei E. P. , Kontos H. A. , Povlishock J. T. , Ellis E. F.
Published: December 2017

The effects of topical application of 15-hydroperoxy-eicosatetraenoic acid (15-HPETE, 200 micrograms/ml) on cerebral arterioles were studied in anesthetized cats equipped with cranial windows. 15-HPETE induced arteriolar dilation during application, sustained dilation 1 h after washout, and reduced responsiveness to the vasoconstrictive effects of hypocapnia. Electron microscopy of cerebral arterioles disclosed discrete endothelial lesions and focal morphological abnormalities of the vascular smooth muscle. Topical application of superoxide dismutase or catalase or the combination of the two inhibited the functional and morphological abnormalities induced by 15-HPETE. The results show that the vascular effects of 15-HPETE are mediated by superoxide anion radical and hydrogen peroxide or by other radicals derived from them, such as the hydroxyl radical. The results, together with earlier findings, support the view that the oxygen radicals responsible for these cerebral vascular effects are generated via the prostaglandin hydroperoxidase reaction.
Baroreflex control of plasma arginine vasopressin in humans
Authors: Leimbach W. N. , Schmid P. G. , Mark A. L.
Published: December 2017

We postulated an interaction between the osmoreceptor and baroreceptor regulation of arginine vasopressin (AVP) release in humans such that the modulating effects of the baroreceptors on AVP release may be undetectable unless the serum osmolality is elevated. We studied normal subjects in both a water-replete (WR, n = 9) and water-deplete (WD, n = 9) state. We monitored blood pressure, central venous pressure, and forearm blood flow. In both WR and WD subjects selective unloading of cardiac baroreceptors with lower body negative pressure (LBNP) -15 mmHg for 30 min did not increase AVP levels. Combined unloading of cardiac and arterial baroreceptors by LBNP -40 mmHg for 10 min significantly increased AVP levels in only the fluid-deplete group [3.54 +/- 0.40 to 8.09 +/- 1.40 (SE) microU/ml, control vs. LBNP -40 mmHg, P less than 0.05]. Mean arterial pressures did not decrease with LBNP -40 mmHg for 10 min. Further analysis of the data based on serum osmolalities (OSM) indicated that LBNP -40 mmHg significantly increased AVP levels (3.72 +/- 0.43 to 13.59 +/- 3.63 microU/ml; P less than 0.05; n = 9) during sessions with OSM greater than 294 mosmol/kg, but not during sessions with OSM less than 294 mosmol/kg (2.85 +/- 0.29 to 4.66 +/- 1.15 microU/ml; P = NS; n = 11). This study demonstrates that significant baroreflex-mediated regulation of vasopressin can occur in humans in the absence of overt hypotension. Second, it reveals an interaction between osmoreceptor and baroreceptor regulation of vasopressin levels in humans such that physiological unloading of cardiac and arterial baroreceptors significantly increases plasma vasopressin levels only when serum osmolality is increased.
Microinjection of vasopressin into the locus coeruleus of conscious rats
Authors: Berecek K. H. , Olpe H. R. , Jones R. S. , Hofbauer K. G.
Published: December 2017

To determine whether vasopressin plays a role in central neural control of cardiovascular function by acting on the locus coeruleus we monitored arterial pressure and heart rate responses to graded injections of vasopressin (1-30 ng, 0.1-0.3 microliter) in the locus coeruleus of conscious, restrained rats. Cannulas were stereotaxically implanted in the locus coeruleus 2-5 days prior to experiment. Injections of vasopressin into the locus coeruleus produced dose-related increases in mean arterial pressure (12 +/- 2 to 57 +/- 6 mmHg) and heart rate (27 +/- 6 to 123 +/- 16 beats/min), which lasted over 1 h at the highest dose. Injection of the antipressor vasopressin antagonist d(CH2)5Tyr(Me) arginine vasopressin (10 ng) into the locus coeruleus blocked the cardiovascular responses to vasopressin. Administration of vasopressin into an area lateral to the locus coeruleus had no effect on mean arterial pressure but produced an increase in heart rate. Equivalent doses of saline, angiotensin II, and norepinephrine (NE) had minimal or opposite (NE) effects on arterial pressure and heart rate. Peripheral alpha-adrenergic blockade with phentolamine and beta-adrenergic blockade with propranolol blocked the cardiovascular responses to injection of vasopressin in the locus coeruleus. These results suggest that vasopressin may act in the region of the locus coeruleus to exert a central action on the cardiovascular system that is mediated by a stimulation of sympathetic outflow.
Morphology of the constricted arteriolar wall: physiological implications
Authors: Greensmith J. E. , Duling B. R.
Published: December 2017

Microvessels undergo complex shape changes during constriction that could have profound implications for control of resistance. We exploited in vitro cannulation techniques in combination with electron microscopy to assess the effects of physiological degrees of vasoconstriction on the size and form of the lumen of isolated rat mesenteric arterioles. Photomicrographs of vasoconstricted vessels revealed that the luminal surface is folded and thrown into longitudinal ridges several hundred microns long. These ridges begin to form and encroach on the lumen as the vessel is constricted. Ridge height may increase to 5-10 microns, and as many as 50 ridges were observed around the circumference of a 70-microns vessel. Ridges are comprised of endothelial cells, basal elastic lamina, and portions of the smooth muscle cytoplasm including thick filaments. The ridges are major determinants of the relationships among stress on smooth muscle contractile elements, intraluminal pressure, and luminal diameter. The ridges may also limit the precision of measurement of microvessel diameter in situ since it is not known whether the apex or the base of the ridge is measured under typical conditions of in vivo microscopy. Our findings emphasize the need for additional detailed study of wall morphology to fully understand the regulation of microvessel flow resistance by smooth muscle function.
Left ventricular function and muscle mechanics in hypertrophied rabbit heart
Authors: Okada T. , Okuyama H. , Mashima H. , Sato H. , Kitamura K.
Published: December 2017

Ventricular contractile performance was studied in relation to wall muscle mechanics in isolated rabbit left ventricles during pressure-overloaded hypertrophy. The isovolumic pressure-volume relation of the hypertrophied ventricle (LVH) shifted to the left and upward from the normal control (NC) (P less than 0.001), but calculated wall stress at each normalized circumferential length decreased in LVH. The pressure-ejection rate relation, determined accurately by velocity control technique, could be adequately approximated by a hyperbola. In LVH, the maximum pressure (Po) was larger (154.3 +/- 17.0 mmHg), whereas the maximum ejection rate (Vej max) was smaller (13.7 +/- 4.2 ml/s, P less than 0.001) than those for NC (127.7 +/- 23.3 mmHg and 22.3 +/- 5.7 ml/s, respectively). The pressure-stiffness relation was linear in both groups, but the vertical axis intercept increased, indicating increased resting stiffness in LVH. Ventricular volume stiffness vs. the mean wall stress relationship of LVH shifted upward, whereas the normalized wall muscle stiffness vs. the mean wall stress relationship of LVH showed a smaller slope. Thus the hypertrophied ventricle can maintain its pumping ability at normal or augmented levels with depressed contractile function of the wall muscle.
Effects of Na+ and K+ on protein adsorption on red blood cell surface
Authors: Kikuchi Y. , Koyama T.
Published: December 2017

Effects of Na+ and K+ in plasma on the protein adsorption on red blood cells (RBCs) were studied using fresh human blood and human plasma albumin labeled with a radioactive isotope. Crystalline NaCl and/or KCl were added to blood samples containing labeled albumin so that the plasma osmolarity was increased to final values of 350, 400, and 450 mosmol. The number of albumin molecules adsorbed on the RBCs increased markedly with increases in Na+ but remained unaltered or increased only slightly with increases in K+. The distribution of Na+ and K+ around the RBC membrane was considered to contribute to increasing the adsorption of albumin on the outer surface and to restricting the deposition of hemoglobin on the inner surface with a consequent positive effect on maintaining the stiffness and flexibility of the membrane. In support of this hypothesis the ouabain treatment of RBCs resulted in a decrease in the cellular deformability.
Role of acidosis in early contractile dysfunction during ischemia: evidence from pHo measurements
Authors: Weiss J. , Couper G. S. , Hiltbrand B. , Shine K. I.
Published: December 2017

To investigate the contribution of acidosis to contractile dysfunction during early myocardial ischemia, miniature intramyocardial pH electrodes (0.2 mm tip diam) were used to correlate changes in extracellular pH (pHo) with tension in the isolated arterially perfused rabbit interventricular septum. A number of findings argue against acidosis as the major cause of contractile failure during early ischemia. During hypoxia without glucose present, the rate and pattern of tension decline was very similar to total ischemia, suggesting that a common mechanism is involved. Throughout the initial period in which tension declined by 50%, however, pHo increased in the six of eight preparations during hypoxia without glucose. During hypoxia with glucose present, tension fell less rapidly than during hypoxia without glucose despite a significantly greater fall in pHo in the former case. The maximal rate of relaxation (-dT/dt) was markedly more sensitive to ischemia, hypoxia, or exposure to inhibitors of aerobic metabolism (2,4-dinitrophenol and Na azide) than the maximal rate of force development (+dT/dt). In contrast, +dT/dt and -dT/dt decreased almost symmetrically during exposure to respiratory acidosis. During ischemia, the change in pHo associated with 50% reduction in tension was 0.11 +/- 0.04 units. During respiratory acidosis, this value was 0.45 +/- 0.02 units. From these observations we concluded that acidosis is unlikely to be a major factor in the early decline of tension during ischemia.
End-systolic pressure-length relations during changes in regional contractile state
Authors: Kaseda S. , Tomoike H. , Ogata I. , Nakamura M.
Published: December 2017

End-systolic pressure-length relationship (ESPLR) was examined in the heterogenously contracting heart in open-chest dogs. Regional length was measured sonomicrometrically in the areas of both the left circumflex coronary artery (LCX) and left anterior descending coronary artery (LAD). ESPLR was linear during a transient reduction in arterial pressure following occlusion of the inferior caval vein (IVC). In group 1 (12 dogs), saline as a control condition (Cont) and isoproterenol (Iso, 0.05 microgram/min) to enhance the regional contractile state were infused into the LCX. Percent shortening in the LCX area increased from 13 to 16% (P less than 0.01) in Iso. The slope (Ees) of ESPLR increased from 57 to 71 mmHg/mm (P less than 0.01) in Iso. The extrapolated X-axis intercept (Lo) of ESPLR was unchanged. In the LAD area, Ees and Lo remained constant. In group 2 (13 dogs), lidocaine (1 mg/min, Lid 1; 5 mg/min, Lid 5) was infused into the LCX to induce mild and severe hypokinesis, respectively. Percent shortening in the LCX area was reduced from 14 to 8% (P less than 0.01 vs. Cont) in Lid 1 and 5% (P less than 0.01 vs. Cont, P less than 0.05 vs. Lid 1) in Lid 5. Ees tended to decrease in Lid 1 but to increase in Lid 5 (statistically not significant).(ABSTRACT TRUNCATED AT 250 WORDS)
Decreased defibrillator-induced dysfunction with biphasic rectangular waveforms
Authors: Jones J. L. , Jones R. E.
Published: December 2017

High-intensity electric shocks used for cardiac defibrillation produce arrhythmias, S-T segment changes, and a low percent success in situ. Cultured myocardial cells exhibit similar postshock arrhythmias that are caused by a prolonged depolarization of the cell membrane. Since this dysfunction is ameliorated by biphasic RLC-type waveforms, we examined rectangular biphasic waveforms to maximize this beneficial effect and clarify the dysfunction-inducing mechanism. Cultured myocardial cells were subjected to electric field stimulation with monophasic 5-ms rectangular waveforms of about 80 V/cm to produce a postshock arrest of contractile activity lasting 4 s. Shocks given with this control waveform were alternated with biphasic test waveforms having the same initial portion followed by negative "tails" 1-100 ms in duration and 5-100% of the initial positive portion in amplitude. Results from 31 biphasic waveforms demonstrated significant alterations in postshock dysfunction. Waveforms with up to 10% undershoot and ranging from 5 to 100 ms in duration decreased arrest time by up to 50%; waveforms with greater than 20% undershoot led to protracted postshock arrest times. These results strengthen the hypothesis that electromechanical breakdown of the myocardial cell membrane underlies postshock dysfunction and show that biphasic waveforms with low amplitude tails ameliorate this dysfunction.
Contribution of sodium to the mechanism of one-kidney, renal-wrap hypertension
Authors: Haywood J. R. , Williams S. F. , Ball N. A.
Published: December 2017

The early and chronic stages of one-kidney, figure-8 renal-wrap hypertension were studied during low or normal dietary sodium intake in rats. The renal-wrap procedure caused a significant elevation in arterial pressure at 3 and 28 days postwrap with normal sodium diet. Sodium-depleted rats did not experience an increased arterial pressure following renal wrapping. Blockade of angiotensin II receptors with [Sar1-Ala8]angiotensin II caused a greater decrease in arterial pressure in the sodium-depleted, renal-wrapped animals compared with sham-operated rats. In sodium-replete rats, angiotensin receptor blockade did not lower arterial pressure. Total ganglionic blockade decreased arterial pressure significantly more in the wrapped animals than in the sodium-replete sham-operated rats and the wrapped or sham-wrapped, sodium-deplete animals. Thus the early and chronic phases of normal sodium, one-kidney, figure-8 renal hypertension are supported by an increased sympathetic nervous system function. These observations suggest that sodium is necessary for the development of one-kidney, figure-8 renal-wrap hypertension and that the presence of sodium in the diet permits a functional activation of the sympathetic nervous system in response to the renal-wrap procedure.
O2 reserve of left ventricle of isolated, saline-perfused rabbit heart
Authors: Paradise N. F. , Surmitis J. M. , Mackall C. L.
Published: December 2017

The heart from the pentobarbital-anesthetized rabbit was isolated, and a fluid-filled balloon was placed in the left ventricular chamber for assessment of isovolumic pressure development. The bicarbonate-buffered, physiological perfusate was aerated initially with 95% O2-5% CO2, and then progressive decreases in arterial O2 content (CaO2) were produced in a stepwise fashion by substituting N2 for O2 in the aerating gas mixture. If, for a specified set of experimental conditions, no change in ventricular function occurred after the initial decrease in CaO2, it was concluded that the heart was oxygenated adequately prior to the first CaO2 decrement. Accordingly, with perfusate flow constant at 35 ml/min, adequate oxygenation was achieved during aeration of perfusate with 95% O2 when ventricular contraction rate was 30 beats/min and temperature (T) 22 degrees C. The preparation may have been just marginally O2 sufficient when rate was 60 beats/min (T, 25 or 30 degrees C), but probably was hypoxic when contraction rate was 120 beats/min (T, 30 or 37 degrees C). Perfusion with pressure kept constant at 80 mmHg did not appear to alleviate this hypoxia when metabolism was elevated (rate, 120 beats/min; T, 37 degrees C). Thus, unless the contraction rate is very low, the addition of an O2-carrying vehicle to the perfusate appears to be necessary if O2 delivery to the isolated rabbit heart preparation is to be supramaximal.
Persistent coronary vasodilation during long-term, supramaximal doses of adenosine
Authors: Crystal G. J. , Downey H. F. , Bashour F. A.
Published: December 2017

Active and reactive hyperemias have been observed in the skeletal muscle circulation tachyphylactic to exogenous adenosine following 3-h supramaximal doses of the vasodilator. These findings failed to support a need for adenosine in metabolic control of skeletal muscle blood flow. The present study was conducted to determine if the coronary circulation also develops tachyphylaxis to adenosine while remaining sensitive to other metabolically linked vasodilator mechanisms. Experiments were conducted in eight pentobarbital-anesthetized, open-chest dogs whose blood flow in the left anterior descending coronary artery (LAD) was measured electromagnetically during 3-h infusion of adenosine into the LAD. Measurements of regional myocardial blood flow (radioactive microspheres), myocardial O2 consumption (Fick principle), and percent segment shortening (ultrasonic crystals) were also obtained. Adenosine was infused into the LAD at a rate of 27.0-72.0 mumol/min, depending on blood flow rate. Calculated concentration of adenosine in LAD blood averaged 0.484 +/- 0.111 mumol/ml, which was well in excess of that required for maximal coronary vasodilation. LAD blood flow averaged 21.5 +/- 2.2 ml/min during the preadenosine control condition. LAD blood flow after 3 h adenosine (123.3 +/- 23.0 ml/min) was not significantly different from that after 1-3 min adenosine (105.8 +/- 17.9 ml/min). There was no significant transmural variation in LAD blood flow during adenosine infusion. Adenosine had no significant effect on myocardial O2 consumption or percent segment shortening. Our results demonstrate persistent transmural vasodilation in the canine coronary circulation during long-term, supramaximal doses of adenosine and are consistent with a role for endogenous adenosine in maintenance of coronary vasodilation during sustained elevations in myocardial energy demands.
A technique for monitoring blood flow changes with miniaturized Doppler flow probes
Authors: Van Orden D. E. , Farley D. B. , Fastenow C. , Brody M. J.
Published: December 2017

A method for constructing miniaturized Doppler blood flow probes is presented. Since these probes weigh less than 100 mg and have crystal heads less than 0.5 mm in size, they are suitable for chronic placement on vessels as small as 200 micron. The probes are positioned under the vessel and rotated to optimize the Doppler signal. While held in that position, the crystal head is attached to the adventitia of the vessel with cyanoacrylate glue. A cuff holding the vessel and probe in the chosen position is then formed in situ by the application of a drop of silicone polymer. Data are presented showing the linearity of a flow probe response with the volume blood flow at rates as low as 14 microliter/min. With the use of the uterine artery of the conscious, unrestrained rat as an example, the probe was demonstrated to detect a dynamic change in flow.
Method for measurement of heart rate in awake, noninstrumented small mammals
Authors: Vetterlein F. , Sammler J. , dal Ri H. , Schmidt G.
Published: December 2017

A method is described that enables the researcher to determine the heart rate in awake, noninstrumented small animals by recording the electrocardiogram (ECG) via the paws. Single animals are placed in a cage that has metal plates built into its floor. Through switches any two plates can be connected with an ECG recorder whenever contact with at least one front and one hind paw is made. The heart rate is then determined by measuring the number of R waves per unit of time. In rats of 140 and 300 g body wt mean resting heart rates of 384 +/- 10 and 320 +/- 4 beats/min, respectively, have been measured with this method.
Repetitive ramped neck suction: a quantitative test of human baroreceptor function
Authors: Ebert T. J. , Hayes J. J. , Ceschi J. , Kotrly K. J. , van Brederode J. , Smith J. J.
Published: December 2017

Bolus intravenous injection of an alpha-agonist is a widely accepted method used for studying baroreceptor function. However, the method is invasive, multiple baroreceptor regions are stimulated, and there are diverse direct effects of these pharmacologic agents, e.g., direct effects on the carotid sinus region. A recently described noninvasive neck suction technique may be highly specific for assessing the carotid sinus to sinoatrial node baroreflex. We compared neck suction-derived baroslopes with those obtained from the standard, invasive phenylephrine infusion method. These techniques were applied to 15 adult volunteers while awake and during 1.34 and 2% isoflurane anesthesia. The correlation coefficients between the two methods were 0.74 (P = 0.002) in awake subjects and 0.75 (P = 0.001) overall. The neck suction method of repetitive, ramped carotid stimuli yielded results that were qualitatively and quantitatively similar to those of the standard phenylephrine method. The neck suction method is simple, noninvasive, and can be repeated at frequent intervals. This method may be highly specific for determining carotid baroreceptor-cardiac reflex physiology in humans.
Regional differences in alpha 1-adrenoceptor numbers and responses in canine aorta
Authors: Griendling K. K. , Sastre A. , Milnor W. R.
Published: December 2017

The relationship between active force and alpha 1-adrenergic receptor binding in vascular smooth muscle was measured on strips of canine aorta. After measurement of the isometric force produced by l-phenylephrine and l-norepinephrine in vitro, [3H]prazosin was used to determine the affinity and numbers of alpha 1-receptors in homogenates prepared from the strips. Maximum active stress was 440 g/cm2 in the ascending, 317 in the descending thoracic, and 252 in the abdominal aorta. The total number of alpha 1-receptors per gram arterial wall averaged 576, 237, and 136 fmol/g, respectively. Affinity of the receptors was the same in all regions for prazosin (87 pM) and l-phenylephrine (9 microM). The relation between number of agonist-occupied receptors and response was similar in all regions but nonlinear; 50% of the maximum stress developed when only 2–11% of the receptors were occupied. Differences of contractile response within the vascular tree may thus arise from regional differences in the number of appropriate receptors present, rather than differences of affinity or occupation-response relationships.
Cycle length-dependent action potential duration in canine cardiac Purkinje fibers
Authors: Elharrar V. , Atarashi H. , Surawicz B.
Published: December 2017

We studied the effects of pharmacologic probes that affect predominantly the Na inward current [tetrodotoxin (TTX), lidocaine], the slow inward current [cobalt, isoproterenol, verapamil], and the potassium currents [tetraethylammonium chloride (TEA), SG-75] on the duration of the action potential (APD) of canine cardiac Purkinje fibers during steady state and restitution. A schema is proposed in which the APD during steady state or restitution is determined by three factors: maximum action potential duration (APDmax), kinetics of restitution, and “memory.” The predicted APDmax was 469 +/- 34 (SE) ms (n = 27) in control. It was prolonged (P less than 0.05) by cobalt, verapamil, and TEA and shortened (P less than 0.05) by TTX, lidocaine, isoproterenol, and SG-75. In control, the kinetics of restitution were described by a sum of two exponentials with time constant T1 = 137 +/- 9 ms and T2 = 1,665 +/- 135 ms (n = 27), respectively. T1 was prolonged (P less than 0.05) by TTX, lidocaine, and verapamil but was not changed by other probes. None of the probes studied altered the T2 of restitution or the memory factor, computed at a cycle length of 500 ms from the predicted APDmax and the plateau of restitution. Low temperature (31 degrees C) prolonged APDmax and T1 and reduced the memory. We conclude that each of the proposed three factors is controlled by different mechanisms and that a TTX-sensitive current appears to contribute to the process of restitution of APD.
Hypertension after ending captopril administration: pathogenesis in 2-kidney, 1-clip rat
Authors: DeForrest J. M. , Creekmore J. S. , Ferrone R. A.
Published: December 2017

We have previously shown that continuous captopril administration prevents hypertension from developing in the two-kidney, one-clip (2K, 1C) rat. The present investigation was designed to determine the mechanism(s) producing the hypertension. In one series of experiments captopril prevented pressure from increasing during an 8-wk treatment period. Relative to the last day of treatment, mean arterial pressure and total peripheral resistance (TPR) were increased and cardiac output was unchanged at 3, 7, and 28 days after captopril cessation. Plasma renin activity (PRA) was unchanged 3, 7, and 14 days after captopril cessation but was elevated at 28, 49, and 56 days after captopril cessation only in 2K, 1C rats with severe hypertension (systolic blood pressure greater than 180 mmHg). Guanethidine (45 mg/kg po, bid) did not prevent the development of 2K, 1C hypertension but did prevent the hypertension from developing after cessation of captopril. Blockade of the prostaglandin system with indomethacin (5 mg/kg + 50 micrograms X kg-1 X min-1) and of the kallikrein-kinin system with aprotinin (25,000 KIU + 150 KIU X kg-1 X min-1) for 2 h had no effect on captopril's antihypertensive effect. Additionally, no change in sodium or water balance was observed after captopril cessation. Taken together these data demonstrate that hypertension after captopril cessation is due to an increase in TPR. Additionally, the rise in TPR is due to both the sympathetic nervous and the renin-angiotensin systems since both systems must be functional before pressure rises.
Adenosine antagonist aminophylline attenuates pacing-induced coronary functional hyperemia
Authors: Randall J. R. , Jones C. E.
Published: December 2017

The role of adenosine in pacing-induced hyperemia was examined in 10 dogs. Left coronary blood flow (LCBF), left ventricular O2 extraction [(a-v)O2], and myocardial O2 consumption (MVO2) were monitored. Heart rate (HR) was initially paced at 120 beats/min and then increased to 180 beats/min to elicit a hyperemic response (delta LCBF). During the hyperemia, the vasodilatory response to exogenous adenosine (FAd) was tested. HR was then returned to the initial level, and 20 min after injection of aminophylline (100 mg iv) HR was again increased to 180 beats/min. The response to adenosine was again tested. The pacing-induced increase in MVO2 (delta MVO2) was not affected by aminophylline (P greater than 0.05). However, after aminophylline, the flow response slope delta LCBF/delta MVO2 was decreased by about 20% (P less than 0.05), and the extraction-response slope delta (a-v)O2/delta MVO2 was increased by 100% (P less than 0.05). FAd was also decreased by aminophylline, and the magnitude of the reduction was correlated with the decrease in the flow-response slope (r = 0.82). These results suggest that endogenous adenosine may play an important role in coronary functional hyperemia induced by increases in heart rate.
Cellular Ca2+ monitored by aequorin in adenosine-mediated smooth muscle relaxation
Authors: Bradley A. B. , Morgan K. G.
Published: December 2017

We studied the effect of adenosine on cytoplasmic ionized calcium-force relationships in vascular smooth muscle (VSM) and determined the dose dependence of the observed effects. The bioluminescent protein aequorin was used as an index of cytoplasmic ionized calcium and was chemically loaded into ferret portal vein strips. The VSM strips were contracted with 33 mM potassium (K+), 5 X 10(-6) M phenylephrine (PE), or electrical stimulation. Force and aequorin light, i.e., cytoplasmic ionized calcium, were simultaneously recorded. Adenosine pretreatment (3.7 X 10(-6) M) reduced both force and light responses in contractures with K+, PE, or electrical stimulation. In contrast, the addition of adenosine during PE or K+ contractions decreased force without a change in light. Dose-response curves for the effects of adenosine on K+ contractures indicated that at low doses adenosine decreases force and cytoplasmic ionized calcium but that at high concentrations (greater than 3.7 X 10(-6) M) adenosine increases light and apparently relaxes VSM by desensitizing the myofilaments to cytoplasmic ionized calcium.
Assessment of autonomic function in humans by heart rate spectral analysis
Authors: Pomeranz B. , Macaulay R. J. , Caudill M. A. , Kutz I. , Adam D. , Gordon D. , Kilborn K. M. , Barger A. C. , Shannon D. C. , Cohen R. J. , et al.
Published: December 2017

Spectral analysis of spontaneous heart rate fluctuations were assessed by use of autonomic blocking agents and changes in posture. Low-frequency fluctuations (below 0.12 Hz) in the supine position are mediated entirely by the parasympathetic nervous system. On standing, the low-frequency fluctuations increase and are jointly mediated by the sympathetic and parasympathetic nervous systems. High-frequency fluctuations, at the respiratory frequency, are decreased by standing and are mediated solely by the parasympathetic system. Heart rate spectral analysis is a powerful noninvasive tool for quantifying autonomic nervous system activity.
Presynaptic modulation of acetylcholine release from cardiac parasympathetic neurons
Authors: Wetzel G. T. , Brown J. H.
Published: December 2017

Acetylcholine can be released from parasympathetic nerve endings in rat atria by 57 mM K+ depolarization or by electrical field stimulation. We have studied the presynaptic modulation of [3H]acetylcholine release from superfused rat atria prelabeled with [3H]choline. Exogenous acetylcholine and the specific muscarinic agonist oxotremorine inhibit the stimulation-induced overflow of [3H]acetylcholine into the superfusion medium. The half-maximal inhibitory concentration (IC50) of oxotremorine is 0.3 microM. The cholinesterase inhibitor neostigmine also decreases K+-stimulated [3H]acetylcholine overflow, whereas the muscarinic antagonist atropine enhances the overflow of [3H]acetylcholine. These data suggest that acetylcholine release in atria is modulated through negative feedback by the endogenous transmitter. The sympathetic adrenergic neurotransmitter norepinephrine and the neurohormone epinephrine also inhibit the overflow of [3H]acetylcholine by approximately 60%. The IC50 values for the inhibitory effects of these catecholamines are 6.3 and 2.2 microM, respectively. The inhibitory effect of norepinephrine is blocked by the alpha-adrenergic receptor antagonist yohimbine but not by the beta-adrenergic receptor antagonist propranolol. We suggest that presynaptic muscarinic and alpha-adrenergic receptors participate in the physiological and pharmacological control of cardiac parasympathetic activity.
Oxygen dependence of energy metabolism in contracting and recovering rat skeletal muscle
Authors: Idstrom J. P. , Subramanian V. H. , Chance B. , Schersten T. , Bylund-Fellenius A. C.
Published: December 2017

The relationship between the oxygen supply and the energy metabolism in perfused rat hindlimb muscles was evaluated both during contractions and during recovery from contractions. The 31P-nuclear magnetic resonance (NMR) technique and conventional biochemical methods were used. Significant correlations were found between the oxygen delivery and the oxygen consumption, lactate release and glucose uptake, respectively. An increased degree of fatigue was observed at the lower oxygen deliveries. In both the soleus and gastrocnemius muscles the oxygen delivery correlated with the intramuscular concentrations of phosphocreatine, lactate, and glycogen. The 31P-NMR experiments showed a correlation between the oxygen delivery and the steady-state level of the phosphocreatine-to-inorganic phosphate (PCr+Pi) ratio during the contraction period. The rate of recovery in PCr/Pi after the contractions was also dependent on the oxygen delivery. The results demonstrate a causal relationship between the oxygen supply and the energy state in contracting as well as recovering skeletal muscles.