bluuebunny/crossref_metadata_2025 huggingface dataset:
The mitochondrial adenosine 5'-triphosphatase in slow and fast heart rate hearts
Authors: Rouslin W.
Published: December 2017

A survey of 12 species has revealed that reversible ischemia-induced protonic inhibition of the cardiac muscle mitochondrial adenosine 5'-triphosphatase (ATPase) described by this author earlier (Rouslin, W. J. Biol. Chem. 258: 9657-9661, 1983) occurs only in animals with heart rates lower than approximately 200 beats/min. It was thus fully demonstrable in rabbit, dog, sheep, human, pig, and beef heart mitochondria. In contrast, the in situ ATPase inhibition was completely absent in six smaller species capable of heart rates of approximately 300 or more beats/min. These were chicken, pigeon, guinea pig, rat, hamster, and mouse. Analyses of the cardiac muscle mitochondria of 9 of the 12 species studied showed them to contain normal levels of mitochondrial ATPase inhibitor; the three smallest species, rat, hamster, and mouse contained only very low levels of inhibitor. Thus, although chicken, pigeon, and guinea pig heart mitochondria contained normal levels of ATPase inhibitor, they (like the rat, hamster, and mouse) showed no in situ ischemia-induced ATPase inhibition. This and other observations suggest that the lack of in situ ATPase inhibition in hearts capable of 300 or more beats/min may be due to the presence of either an in situ nonfunctional ATPase inhibitor protein or to an in situ uninhibitable form of the mitochondrial ATPase in the faster-paced hearts. Alternatively, the mitochondria of the fast-paced hearts may be insulated somehow against the cytosolic acidosis which develops during ischemia and which triggers the ATPase inhibition in the slow heart-rate hearts. In the faster paced hearts, ATP hydrolysis does not appear to be regulated by inhibitor binding to the ATPase under nonenergizing conditions.
Atrioventricular interactions: a theoretical simulation study
Authors: Beyar R. , Sideman S.
Published: December 2017

A quantitative model that describes the complex atrioventricular interactions, based on the structure and myocardial properties of the left atrium (LA) and left ventricle (LV), is presented. The description of the LV follows our earlier study that assumes a nested-shell spheroidal structure with fanlike fiber angle distribution, transmural electrical activation velocity, and the muscle fiber dynamics with the classical passive and active features of the sarcomeres. The LV model is extended here to include an exponential load-dependent relaxation and viscous (strain rate-dependent) features of the LV passive myocardium. The proposed LA model is based on a thin-wall spherical geometry with a random fibrous structure. The atrial muscle features differ from the ventricular muscle by being much stiffer in the passive state and weaker but faster in the active state. The LV and LA compartments are connected to a preload and afterload scheme and interconnected by the mitral flow with its inertial properties. The complex interactions between the LA and the LV are thoroughly studied here, and the calculated results are consistent with well-established experimental data.
Component of whole cell Ca current due to electrogenic Na-Ca-exchange in cardiac myocytes
Authors: Hume J. R.
Published: December 2017

A carrier mechanism that mediates an exchange of Na+ for Ca2+ across the cell membrane is believed to be an important regulator of intracellular Ca2+ and therefore the contractile strength of the heart. Considerable evidence indicates that there is an unequal transfer of electrical charge during this exchange which implies that the carrier may contribute substantially to the net flow of ionic current across the sarcolemmal membrane. To detect such a component of current, nondialyzed single frog atrial cells were transiently Ca2+-loaded by augmenting Ca2+ entry through membrane Ca2+ channels by exposure to either the beta-adrenergic agonist, isoproterenol, or to BAY K 8644, a Ca2+ channel agonist. A direct comparison of whole-cell Ca2+ currents during exposure to these compounds in Na+-containing and Na+-free solutions revealed the existence of an additional component of inward current in Na+-containing solutions which temporally overlaps with Ca2+ channel-mediated currents. The dependence of this component of inward current on intracellular Ca2+ and extracellular Na+ and its resemblance to previously characterized carrier-mediated currents (creep currents) in this preparation suggest that it is associated with electrogenic Na+-Ca2+-exchange activity. These experiments support earlier predictions that under some conditions a component of the slow inward current in the heart may actually represent Ca2+ efflux mediated by an electrogenic Na+-Ca2+-exchange carrier.
Endothelium-dependent contraction to stretch in canine basilar arteries
Authors: Katusic Z. S. , Shepherd J. T. , Vanhoutte P. M.
Published: December 2017

Stretch applied to isolated canine basilar arteries caused the development of active tension in rings with endothelium but not in those in which the endothelium had been removed. Blockade of calcium entry with diltiazem or inhibition of cyclooxygenase with indomethacin abolished the endothelium-dependent response to stretch. These observations suggest that the endothelium may contribute to the autoregulation of cerebral blood flow during increases in transmural pressure by the increased production and/or release of prostaglandins, which causes activation of the underlying vascular smooth muscle.
Voltage-dependent effects of isoproterenol on cytosolic Ca concentration in rat heart
Authors: Sheu S. S. , Sharma V. K. , Korth M.
Published: December 2017

The effect of the beta-adrenoceptor agonist, isoproterenol, on cytosolic calcium concentration ([Ca2+]i) was studied with the Ca2+-sensitive fluorescent indicator quin 2 in enzymatically dissociated rat ventricular myocytes. Under conditions in which cells have normal polarized resting membrane potential, isoproterenol (1 microM) produced a decrease in [Ca2+]i. In contrast, in the depolarized cells (by raising extracellular K+ concentration to 50 mM), isoproterenol (1 microM) caused an increase in [Ca2+]i. This isoproterenol-induced increase in [Ca2+]i in depolarized cells could be reversed by prior exposure of the cells to the Ca2+ channel blocker, verapamil (5 microM). The results indicate that isoproterenol can either decrease or increase [Ca2+]i depending on membrane potential. The actual effect of isoproterenol on [Ca2+]i at any given membrane potential probably reflects the relative contributions of isoproterenol-induced stimulation of Ca2+ buffering or effluxing activities (which favor a decrease in [Ca2+]i) and enhancement of Ca2+ influx through voltage-sensitive Ca2+ channels (which favors an increase in [Ca2+]i).
Opioid modulation of baroreceptor reflex sensitivity in dogs
Authors: Szilagyi J. E.
Published: December 2017

Opioid peptides can modulate cardiovascular function both directly and by modifying specific responses. The action of opioids on baroreceptors was evaluated in anesthetized dogs. Baroreceptor responsiveness was determined by observing the peak heart rate and blood pressure responses as well as by evaluating the slope of a line relating heart period to blood pressure while pharmacologically altering blood pressure with doses of phenylephrine hydrochloride and sodium nitroprusside. These tests were performed before and after administration of naloxone (40 micrograms/kg). Naloxone significantly blunted baroreflex function (-55%). Treatment with atropine and vagotomy revealed that the action of naloxone appears to be dually mediated by the parasympathetic and sympathetic nervous systems. These data suggest that opioids can influence baroreflex function in the dog.
Segmental vascular responses to acute hypertension in cerebrum and brain stem
Authors: Faraci F. M. , Mayhan W. G. , Heistad D. D.
Published: December 2017

The goal of this study was to examine hemodynamic mechanisms that contribute to regional differences in autoregulation during acute hypertension. We measured blood flow (microspheres) and pressure in pial arteries (approximately 160 microns) of anesthetized cats and calculated resistance of large and small vessels in cerebrum and brain stem. Moderate elevation of aortic pressure increased resistance of both large and small vessels in cerebrum but only small vessels in brain stem. During severe hypertension, resistance of both large and small vessels in cerebrum decreased and blood flow increased markedly. In contrast, in the brain stem large artery resistance did not change, small vessel resistance increased, and blood flow increased only modestly during severe hypertension. Pial artery pressure was 20 mmHg higher in brain stem than cerebrum during control conditions and 30-50 mmHg higher during moderate and severe hypertension. We conclude that resistance of large arteries is less and thus pial artery pressure is higher in brain stem than cerebrum under control conditions. More effective autoregulation in the brain stem than cerebrum during severe hypertension is due to greater resistance of small, not large, cerebral vessels.
Fluorodeoxyglucose rate constants, lumped constant, and glucose metabolic rate in rabbit heart
Authors: Krivokapich J. , Huang S. C. , Selin C. E. , Phelps M. E.
Published: December 2017

The isolated arterially perfused rabbit interventricular septum was used to measure myocardial metabolic rate for glucose (MMRGlc) and rate constants and lumped constant (LC) for the glucose analogue [18F]fluorodeoxyglucose (FDG) using a tracer kinetic model. FDG was delivered by constant infusion during coincidence counting of tissue 18F radioactivity. The MMRGlc was measured by the Fick method. Control septa were paced at 72 beats/min and perfused at 1.5 ml/min with oxygenated perfusate containing 5.6 mM glucose and 5 mU/ml insulin. The following conditions were tested: 3.0 and 4.5 ml/min; insulin increased to 25 mU/ml; insulin omitted; 2.8 mM and 11.2 mM glucose; 144 beats/min and 96 paired stimuli/min; and anoxia. Under all conditions studied the phosphorylation (hexokinase) reaction was rate limiting relative to transport. Compared with control conditions, the phosphorylation rate constant was significantly increased with 2.8 mM glucose as well as in anoxia. With 4.5 ml/min and 11.2 mM glucose, conditions that should increase glucose flux into tissue without increasing demand, the phosphorylation rate constant decreased significantly. With 11.2 mM glucose, 96 paired stimuli/min, and anoxia without insulin, a significant increase in the hydrolysis rate of FDG 6-phosphate was observed and suggests that hydrolysis is also an important mechanism for regulating the MMRGlc. Increased transport rate constants were observed with increased flow rates, 96 paired stimuli/min, and anoxia at 96 beats/min. The LC was not significantly different from control in 11 of 14 conditions studied. Therefore, under most conditions, an average LC can be used to calculate MMRGlc estimates.
Sympathetic function in spontaneously hypertensive rats after chronic administration of captopril
Authors: Berecek K. H. , Kirk K. A. , Nagahama S. , Oparil S.
Published: December 2017

The cardiovascular effects of electrical stimulation of the posterior hypothalamus, intravenous administration of norepinephrine (NE), and direct sympathetic nerve stimulation (SNS) were compared in spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) given captopril (osmotic minipump, 1.25 micrograms/h icv) or vehicle for 4 wk beginning at age 7 wk. Mean arterial pressure (MAP) and renal and mesenteric flows (pulsed Doppler flow probes) were monitored in anesthetized rats. Following chronic administration of captopril the MAP was 141 +/- 4 mmHg in SHR receiving captopril and 183 +/- 6 mmHg in SHR receiving vehicle. Posterior hypothalamic stimulation, intravenous NE, and SNS resulted in lesser increases in MAP and renal and mesenteric vascular resistances in SHR treated with captopril. Response curves were shifted to the right, and the initial slopes and rate of change of slopes of the curves were less in captopril-treated SHR than vehicle-treated rats. The decrease in sensitivity to posterior hypothalamic stimulation was greater than the decrease in response to NE or SNS. The decrease in vascular reactivity in captopril-treated SHR was not due to increased sensitivity of the baroreflex for control of vascular resistance nor to a decrease in arterial pressure per se. WKY treated with captopril also showed lesser increases in MAP and renal and mesenteric vascular resistances in response to posterior hypothalamic stimulation, intravenous NE, and SNS. The depressor effects of intracerebroventricular captopril in SHR may be due, in part, to an attenuation in sympathetic vasoconstrictor tone. This attenuation involves both a decrease in vascular smooth muscle responsiveness to NE as well as a decrease in central stimulation of sympathetic outflow.
Effects of pregnancy on cardiac function and myosin enzymology in the rat
Authors: Buttrick P. M. , Schaible T. F. , Malhotra A. , Mattioli S. , Scheuer J.
Published: December 2017

Previous studies of cardiac function during pregnancy, while suggesting that this condition is associated with improved myocardial contractility, have been biased by the altered in vivo loading conditions. Therefore, we have investigated intrinsic cardiac function and contractile protein biochemistry during pregnancy in isolated rat hearts under controlled loading conditions. Animals were impregnated and studied after 1 and 3 wk and 2-3 days postpartum (gestation 21 days). The data show that hearts from pregnant animals (at 3 wk) had improved contractile performance as manifested by an 11% increase in fractional shortening, a 20% increase in velocity of circumferential fiber shortening, and an upward-shifted force-velocity relationship. These findings were paralleled by a 16% increase in Ca2+-activated myosin and an 11% increase in actin-activated ATPase activities. Thus pregnancy in the rat is associated with slightly improved cardiac contractility and biochemistry. This may relate directly to the hormonal status of the pregnant animal or to the effects of chronic volume overload.
Calcium currents of cardiovascular neurons isolated from adult guinea pigs
Authors: Kunze D. L.
Published: December 2017

A preparation of cells isolated from the medial and dorsal nuclei of the solitary tract of the medulla of adult guinea pigs was developed to examine the electrical properties of neurons isolated from an area of the central nervous system which is involved in the control of arterial pressure and heart rate. Bipolar cells of approximately 10 microns diameter were obtained on enzymatic dispersion. The cells were studied with the use of the patch technique for whole cell recording. Action potentials were elicited by depolarizing pulses in the presence of 10(-5) M tetrodotoxin which blocked a sodium-dependent current. These action potentials were calcium dependent and were eliminated by adding 1 mM Cd to the bath. In all cells studied, two voltage-dependent components to the calcium current were identified. In 10 mM Ca a high-threshold component activated at approximately -20 mV from holding potentials of -30 mV. A second lower threshold component was activated at -40 mV from more negative holding potentials of -80 mV. The low-threshold component was rapidly inactivating, whereas the high-threshold current slowly inactivated. The peak amplitudes of the two components were similar. Both components were blocked by 1 mM Cd. A role for the low-threshold calcium current in generating repetitive activity is postulated.
Effects of ventricular pacing on finite deformation in canine left ventricles
Authors: Waldman L. K. , Covell J. W.
Published: December 2017

Despite the fact that myofibers would be expected to shorten only along their axes, there is now evidence for substantial deformation away from the local myofiber direction in the left ventricle. To determine if the principal directions of deformation could be altered by a physiological stimulus, we examined local three-dimensional finite deformation in the anterior free wall of the left ventricle during normal atrial activation (AA) and, subsequently, during epicardial ventricular pacing (VP) at the site of deformation measurement in open-chest anesthetized dogs. An analysis of variance by repeated measures revealed the following significant changes (P less than or equal to 0.05) in the overall (average of epicardial and endocardial data) strain variables at end systole. Circumferential strain increased from -0.07 (AA) to 0.14 (VP), radial strain decreased from 0.16 (AA) to 0.01 (VP), shear in the tangent plane of the local epicardium decreased from 0.04 (AA) to -0.02 (VP), shear in the plane of the longitudinal and radial coordinates decreased from 0.03 (AA) to -0.03 (VP). Neither the first (greatest shortening) nor the third (greatest lengthening) principal strain changed significantly, but the direction of the first principal axis of deformation projected on the epicardial tangent plane changed from -51 degrees (AA) to -80 degrees (VP) from circumferential. In addition, substantial tipping of the plane of principal shortening away from the epicardial tangent plane was observed, particularly with ventricular pacing. These data indicate that the principal directions of deformation can be altered substantially by changing the activation sequence. In conjunction with the observed shearing deformations, particularly near the endocardium, they support the concept that locally the heart wall deforms as a unit with significant transmural tethering.
Free radical-mediated endothelial damage in blood vessels after electrical stimulation
Authors: Lamb F. S. , King C. M. , Harrell K. , Burkel W. , Webb R. C.
Published: December 2017

The endothelium plays an important role in mediating vasodilator effects of several agents (acetylcholine, thrombin, A23187, etc.). The goal of this study was to determine the ability of oxygen free radicals generated by electrical field stimulation to alter endothelial function in isolated tissue systems. Tail artery strips and the mesenteric microvasculature isolated from Sprague-Dawley rats were used. Following smooth muscle contraction induced by norepinephrine, these preparations relaxed in response to acetylcholine chloride or ionophore A23187. All vessels were then subjected to electrical stimulation (9 V, 1-2 ms, 4 Hz) of the physiological buffer in which they were bathed or perfused. In some of these preparations, an antioxidant, (10(-4) M sodium ascorbate, 3.6 X 10(-5) M glutathione, 1.3 X 10(-2) M dimethyl sulfoxide) was included in the buffer. Relaxation responses persisted in vessels where an antioxidant had been included in the electrically stimulated buffer. Tissues stimulated without this protection did not relax on subsequent exposures to endothelium-dependent vasodilators. Scanning-electron microscopy of the tissues revealed significant endothelial damage (cell membrane pitting) in tissues exposed to electrical stimulation without antioxidant protection. These results suggest that electrical stimulation causes endothelial damage in isolated vascular preparations. This seemingly adverse effect proves to be a useful tool for removing the endothelium in studies of isolated vascular tissues.
Formation and release of purine catabolites during hypoperfusion, anoxia, and ischemia
Authors: Van Belle H. , Goossens F. , Wynants J.
Published: December 2017

To answer some of the as yet unresolved questions about the formation, metabolism, and release of purine catabolites in hypoxic myocardium, we compared their release from isolated rabbit hearts during hypoperfusion, anoxia, and after ischemia, with and without nucleoside-transport inhibition. Results provide evidence to suggest the following. Besides the supply-to-demand ratio for O2, other factors may affect the formation of adenosine. The myocyte is the major source of purine catabolites. Adenosine is not produced within the myocyte. Once in the interstitium, adenosine is (largely) taken up in the endothelial cells, where it is catabolized to inosine and hypoxanthine and released that way into the lumen. Some of the adenosine can reach the lumen unchanged through clefts. Nucleoside transport inhibition prevents the escape through the endothelial cells and thus the formation and release of inosine and hypoxanthine. As a consequence, more adenosine will accumulate in the interstitium and more will reach the lumen through the clefts. The pathway, as proposed, explains the long known paradox of increased extracellular levels of adenosine after inhibition of nucleoside transport.
Effects of regional ischemia and ventricular pacing on LV dP/dtmax-end-diastolic volume relation
Authors: Little W. C. , Park R. C. , Freeman G. L.
Published: December 2017

We investigated the effects of coronary artery occlusion and pacing from ventricular sites on the relation of the maximum rate of rise of left ventricular pressure (dP/dtmax) to the end-diastolic volume (VED) in dogs previously instrumented to measure left ventricular pressure and to determine left ventricular volume from three ultrasonically measured dimensions. The dP/dtmax-VED relation was generated by vena caval occlusion and compared with the simultaneously produced end-systolic pressure-end-systolic volume (PES-VES) relation. The dP/dtmax-VED relation was described by a straight line during all conditions. Occlusion of the left circumflex coronary artery produced a rightward shift of the dP/dtmax-VED relation, increasing the volume intercept by 11.3 +/- 5.3 (SD) ml (P less than 0.05). Compared with atrial pacing, the dP/dtmax-VED relation was shifted to the right with the volume intercept increasing by 4.8 +/- 4.4 ml (P less than 0.05) during pacing from the right ventricular free wall, 3.7 +/- 5.0 ml (P less than 0.05) during pacing from the right ventricular apex, and 3.7 +/- 2.4 ml (P less than 0.05) during pacing from the left ventricular free wall. Similar increases were observed in the volume intercepts of the PES-VES relations during coronary occlusion or ventricular pacing. These results are consistent with the predictions of the time-varying elastance model and support its use as a conceptual framework to understand left ventricular performance during isovolumic contraction and at end systole, both in the normal ventricle and the ventricle with regional abnormalities of contraction.
Renal pressor reflex: involvement of sympathetic vasoconstrictor mechanisms
Authors: Faber J. E. , Gettes D. R.
Published: December 2017

We examined whether vasopressin and/or sympathetic vasoconstrictor mechanisms constitute the efferent limb of an afferent renal nerve (ARN)-dependent renal pressor "reflex" produced by acute unilateral renal artery stenosis (RST). Rats that had received sinoaortic denervation (SAD) were implanted with right renal artery occluders and flow probes. After recovery, conscious rats received captopril. Acute RST increased arterial pressure (AP) by 25% and mesenteric and hindquarters resistances by 35 and 51%, respectively. Vasopressin receptor antagonism was without effect on the reflex. Ganglionic blockade (chlorisondamine or trimethaphan) abolished the reflex, as did alfaxalone/alfadolone or urethan-chloralose anesthesia. In an additional study, SAD animals were prepared with chronic T6 spinal cord transection. Increases in AP during RST were unaffected by spinal transection (27 +/- 4 mmHg). However, the increase in hindquarter resistance in the sham-transected animals (57 +/- 12%) was markedly attenuated (19 +/- 4%) in the spinal-transected group. The data suggest that in animals with depressed baroreflexes and renin-angiotensin system responsiveness, acute RST initiates an ARN-dependent pressor reflex with vasoconstrictor nerves comprising the efferent limb of the reflex. The reflex can be integrated at the spinal level and is highly sensitive to anesthesia.
Oxygen metabolites and vasodilator mechanisms in rat cremasteric arterioles
Authors: Wolin M. S. , Rodenburg J. M. , Messina E. J. , Kaley G.
Published: December 2017

The effects of oxygen metabolites (superoxide anion and hydrogen peroxide) on male Wistar rat cremasteric arterioles and the involvement of these species in the mechanism of vasodilation to arachidonic acid and bradykinin were examined by in vivo television microscopy. In the present study, xanthine oxidase-derived oxygen metabolites from endogenous substrates elicited vasodilation that was selectively and almost completely inhibited by catalase but not by superoxide dismutase. These findings implicate hydrogen peroxide as the vasoactive metabolite generated. Topical application of hydrogen peroxide itself on cremasteric arterioles caused concentration-dependent dilation over the range of 10(-7) to 10(-4) M. Responses to hydrogen peroxide concentrations of up to 10(-5) M were completely inhibited by indomethacin, suggesting that hydrogen peroxide-induced increases in vessel diameter are primarily mediated through the production of vasodilator prostaglandins. In this study, we have not found any evidence to suggest that dilator responses to arachidonic acid or bradykinin are mediated through the extracellular generation of oxygen metabolites. Hydrogen peroxide-induced vasodilation might be involved in the events linking the sensing of oxygen tension through intracellular peroxide formation to the production of vasoactive mediators in the cremasteric microcirculation.
Myocyte and endothelial injury with ischemia reperfusion in isolated rat hearts
Authors: Sunnergren K. P. , Rovetto M. J.
Published: December 2017

We determined the time course of ischemic injury, the effects of reperfusion, and the protective effects of prostacyclin, oxygen radical scavengers, and diltiazem on myocardial myocyte and endothelial cell functions in isolated rat hearts. Left ventricular power and coronary microvascular permeability were used as indexes of myocyte and endothelial cell function, respectively. Neither 5- nor 10-min ischemia reperfusion significantly changed power or permeability. However, with reperfusion following 20 and 30 min of ischemia, power was reduced 50 and 60% and permeability increased 70 and 90%. In 30-min ischemic hearts the ischemia-induced increase in permeability was apparent after 4 min reperfusion and further exacerbated at 20 min. Hypoxic reperfusion did not prevent increased permeability. Prostacyclin or a combination of superoxide dismutase, catalase, and mannitol also did not prevent increased permeability, and the radical scavengers did not ameliorate depressed power. In contrast, perfusion with diltiazem during ischemia reperfusion blunted the reduction in power and prevented the increase in permeability. We conclude that ischemia reperfusion causes similar time course of injury to myocytes and endothelial cells; reperfusion contributes to endothelial injury, and diltiazem affords protection to both cell types.
Postpropranolol vasodilation in adrenalectomized glucocorticoid hypertensive rats
Authors: DiPette D. J. , Burris J. F. , Rogers A. , Waeber B. , Brunner H. R.
Published: December 2017

Acute beta-adrenoreceptor blockade results in an enhanced blood pressure-lowering effect in glucocorticoid hypertensive rats in the absence of the adrenals. To evaluate the possible mechanism of this enhanced blood pressure-lowering effect, systemic and regional hemodynamics were determined by the radioactive microsphere technique before and after propranolol administration in bilaterally adrenalectomized (AX) and sham-operated (SH) glucocorticoid hypertensive rats. Propranolol decreased mean blood pressure (BP) and heart rate (HR) to a greater extent in the AX animals. In response to propranolol, cardiac output (CO) decreased equally in both the AX and SH animals. Regional vascular responses to propranolol were similar between the AX and SH animals, except in muscle. In muscle propranolol significantly decreased blood flow and increased resistance in the SH animals. In marked contrast, in the AX animals propranolol significantly increased blood flow and decreased vascular resistance. The results of this study show that in adrenalectomized glucocorticoid hypertensive rats, the enhanced BP lowering effect of acute beta-adrenoreceptor blockade is not mediated by changes in CO. Additionally, in glucocorticoid hypertensive rats acute beta-adrenoreceptor blockade causes selective vasodilation in skeletal muscle.
Effect of blood pressure on medial medulla-induced muscle atonia
Authors: Lai Y. Y. , Siegel J. M. , Wilson W. J.
Published: December 2017

Stimulation of the medial medullary reticular formation (MMRF) has long been reported to produce generalized inhibition of skeletal muscle activity. However, several studies have reported that in most cases MMRF stimulation produces only increases in muscle tone. In the present investigation we have found that blood pressure is a critical variable, determining whether MMRF stimulation will produce muscle excitation or inhibition. When mean arterial pressure (MAP) was greater than 80 mmHg but less than 148 mmHg, MMRF stimulation produced muscle antonia. Reductions of blood pressure by pharmacological or mechanical techniques induced a reversal of response to MMRF stimulation; stimulation that produced inhibition in base-line conditions produced excitation after MAP reduction. MAP reductions of as little as 10% could cause the reversal response. In contrast, the EMG reduction to MMRF stimulation was not changed or was augmented when MAP was raised. MMRF induced atonia, and its reversal by blood pressure reduction persisted after bilateral isolation of the carotid sinus combined with vagotomy, and in the 6-hydroxydopamine-treated cat. Spinal transection at the cervicothoracic junction did not block atonia or the reversal response. It is suggested that the reversal is mediated centrally.
Substrate use in ischemic and reperfused canine myocardium: quantitative considerations
Authors: Myears D. W. , Sobel B. E. , Bergmann S. R.
Published: December 2017

Page H107: D. W. Myears, B. E. Sobel, and S. R. Bergmann. “Substrate use in ischemic and reperfused canine myocardium: quantitative considerations.” Page H109: unit of measure for NEFA should be μmol/l in Table 1.
Expression of single calcium channels in Xenopus oocytes after injection of mRNA from rat heart
Authors: Moorman J. R. , Zhou Z. , Kirsch G. E. , Lacerda A. E. , Caffrey J. M. , Lam D. M.-K. , Joho R. H. , Brown A. M.
Published: December 2017

Page H985: J. R. Moorman, Z. Zhou, G. E. Kirsch, A. E. Lacerda, J. M. Caffrey, D. M.-K. Lam, R. H. Joho, and A. M. Brown. “Expression of single calcium channels in Xenopus oocytes after injection of mRNA from rat heart.” Page H991: the following should have been included in the acknowledgements: We are grateful to John Leonard and Terry Snutch for their help and advice with the oocyte expression system.
Effects of regional denervation on epicardial DC electrograms during coronary occlusion in pigs
Authors: Cinca J. , Bardaji A. , Figueras J. , Salas-Caudevilla A. , Serrano A. , Rius J.
Published: December 2017

Sympathetic innervation of the normal and acutely ischemic myocardium and the effects of regional myocardial sympathetic denervation of the ischemic area on the evolving electrical changes during coronary occlusion were assessed in pigs anesthetized with pentobarbital sodium. The histofluorescence of the adrenergic nerve fibers (glyoxylic acid reaction), which in the normal myocardium were distributed in a diffuse network, decreased slightly after 45 min of occlusion of the left anterior descending (LAD) coronary artery and nearly disappeared after 2 h of ischemia. Topical application of phenol (carbolic acid, 88%) to the coronary arterial wall produced a transmural loss of catecholamine histofluorescence in the distal myocardium supplied by the phenol-treated arterial segment. Mapping of the epicardial direct current (DC) electrograms in sympathetically denervated and in nondenervated sections of the same ischemic area, using three rows of seven cotton-wick electrodes, was performed in eight pigs and validated in eight other nondenervated pigs. During 45 min of LAD occlusion, the denervated area, with respect to the nondenervated region, showed a greater decline in T-Q segment depression after 20 min of ischemia (P less than 0.0001), a lesser degree of S-T segment elevation throughout the study (P less than 0.0001), a delayed development of monophasic potentials (P less than 0.05), a minor degree of S-T segment alternans (P less than 0.0001), and a less marked, but still present, period of transient electrical recovery. Thus acute regional myocardial sympathectomy reduces the magnitude of the local electrical manifestations of acute myocardial ischemia in the in situ pig heart. Also in this model, sympathetic fibers appeared to lose the catecholamine histofluorescence after 2 h of acute ischemia.
Rectification of muscarinic K+ current by magnesium ion in guinea pig atrial cells
Authors: Horie M. , Irisawa H.
Published: December 2017

Rectifying properties of the acetylcholine (ACh)-sensitive K+ channels were studied using a patch-clamp method in single atrial cells prepared enzymatically from adult guinea pig hearts. In the presence of micromolar concentration of nonhydrolyzable guanosine 5'-triphosphate (GTP) analogue 5'-guanylylimidodiphosphate (GppNHp) and the absence of Mg2+ at the inner surface of patch membrane [( Mg2+]i), the channel activity recovered in inside-out patch condition. The single channel conductance became ohmic between -80 and +80 mV (symmetrical 150 mM K+ solutions). The rapid relaxation of outward single channel currents was disclosed on a depolarization. [Mg2+]i blocked the outward current through the channel dose- and voltage-dependently and also induced a dose-dependent increase in the channel activation. The apparent paradoxical role of [Mg2+]i is important for the cholinergic control in the heart; voltage-dependent Mg block ensures a low K+ conductance of cell membrane at the plateau of action potentials during the exposure to ACh, thereby slowing the heart rate without unfavorable shortening of the action potentials.
Metabolic mediation of single brief diastolic occlusion reactive hyperemic responses
Authors: Sadick N. , Dube G. P. , McHale P. A. , Greenfield J. C.
Published: December 2017

We tested the hypothesis that coronary reactive hyperemia following a single brief diastolic occlusion and subsequent systole is coupled to myocardial metabolic activity and myocardial O2 consumption (MVO2). Sixteen conscious dogs with Formalin-induced heart block were studied. A 400-ms diastolic occlusion was introduced during normal ventricular pacing, resulting in a reactive hyperemic repayment of 216 +/- 22%. A 400-ms diastolic occlusion was also introduced during a higher level of myocardial metabolic activity induced by ventricular paired pacing. MVO2 and mean coronary blood flow were significantly increased relative to these parameters during normal pacing, but reactive hyperemic repayment (189 +/- 18%) was not significantly changed. A third set of conditions was designed to measure the response to a 400-ms occlusion during normal pacing while eliminating the difference in magnitudes of myogenic influences that may exist between paired pacing and normal pacing. Adenosine and phenylephrine were infused intravenously during normal pacing to maintain mean aortic pressure and mean coronary flow at paired pacing levels. MVO2 was similar to O2 consumption during normal pacing in the absence of drug infusion, but the reactive hyperemic repayment was significantly reduced (94 +/- 22%) relative to paired pacing. Thus the magnitude of reactive hyperemic response after a brief diastolic occlusion is related primarily to myocardial metabolic activity.
Relation between oxygen consumption and pressure-volume area of in situ dog heart
Authors: Nozawa T. , Yasumura Y. , Futaki S. , Tanaka N. , Igarashi Y. , Goto Y. , Suga H.
Published: December 2017

We studied the relation between O2 consumption (VO2) and the systolic pressure-volume area (PVA) in the left ventricle of open-chest dogs. PVA and the slope (Emax) of the end-systolic pressure-volume line were determined by an abrupt occlusion of the ascending aorta. VO2 linearly correlated with PVA in control contractile state, where Emax was 15.8 +/- 4.4 (SD) mmHg/ml with intact reflexes and 11.5 +/- 1.2 mmHg/ml with blocked reflexes. Emax and the VO2 axis intercept of the VO2-PVA line were greater in the in situ heart than in the excised cross-circulated dog heart in our previous study. Enhancement of contractile state by dobutamine increased Emax by 60–80% and shifted the VO2-PVA line upward, increasing the VO2 axis intercept by 38% with intact reflexes and by 79% with blocked reflexes. The slope had a tendency to increase with dobutamine, but the increase was statistically insignificant. We conclude that PVA and Emax obtained by the aortic-occlusion method can account for changes in VO2 with changes in loading conditions and contractility in an in situ dog heart.
Modification of sarcolemmal phosphatidylethanolamine N-methylation during heart hypertrophy
Authors: Panagia V. , Okumura K. , Shah K. R. , Dhalla N. S.
Published: December 2017

To evaluate changes in heart sarcolemmal phosphatidylethanolamine (PE) N-methylation, left ventricular hypertrophy was induced in rabbits by banding the abdominal aorta for 4, 8, 14, and 22 wk. The degree of cardiac hypertrophy did not change over the period of time studied. Three catalytic sites involved in the sequential methyl transfer reactions were examined by assaying the incorporation of radiolabeled methyl groups from S-adenosyl-L-methionine (0.055, 10, and 150 microM) into sarcolemmal PE molecules under optimal conditions. Total N-methylation activity at all three sites was significantly increased at 4 wk, unaltered at 8 and 14 wk, and depressed at 22 wk after banding the aorta. Similar biphasic changes were seen for the individual methylated lipid products (monomethylphosphatidylethanolamine, dimethylphosphatidylethanolamine, and phosphatidylcholine) specifically formed at each catalytic site. At all three sites, alterations in PE N-methylation at 22 wk were associated with changes in Vmax values without any change in the apparent affinity for S-adenosyl-L-methionine. In contrast to sarcolemma, a significant increase of the PE N-methylation activity at sites I and III was observed in the sarcoplasmic reticular (microsomal) fraction from 22-wk hypertrophied hearts; the increase in site II was not significant. On the other hand, no changes in the N-methylation activity of the mitochondrial fraction were seen at 22 wk after banding. These findings indicate the occurrence of biphasic alterations in the sarcolemmal PE N-methylation activity during the presence of a stable degree of hypertrophy.
Enhanced myocardial depression in diabetic rats during E. coli sepsis
Authors: McDonough K. H. , Barbee R. W. , Dobrescu C. , Lang C. H. , Spitzer J. J.
Published: December 2017

The aim of this study was to determine whether diabetes enhanced the sensitivity of the myocardium to the deleterious effects of in vivo-administered Escherichia coli. Diabetes was induced in two groups of animals. One group received 70 mg/kg streptozotocin (iv) and exhibited a severe diabetes with elevated fasting and fed blood glucose concentrations and a markedly abnormal response to an oral glucose load. The second group received 45 mg/kg streptozotocin, was mildly diabetic (termed “latent” diabetes), and was characterized by normal fasting blood glucose but slightly elevated fed blood glucose and an abnormal response to a glucose load. A third group of rats received vehicle and served as time-matched control animals. Four weeks after induction of diabetes, all animals were catheterized under ether anesthesia and some received intraperitoneal injections of live E. coli. In vitro myocardial performance was assessed using the isolated, perfused working heart preparation. Ventricular function curves were generated by changing left atrial filling pressure and measuring changes in heart rate, cardiac output, and aortic peak systolic pressure. Cardiac performance in the severe diabetic group was depressed at the highest preload but was unchanged at lower preloads. Function in the latent diabetic group was not different from control. Sepsis induced a slight decrease in cardiac performance in the control group and resulted in larger reductions in the latent and severe diabetic groups. A depression in aortic flow was the major consequence of sepsis in the latent diabetic group, whereas decreased coronary flow was the primary change in the severe diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)
Measurement of interstitial fluid pressure in dogs: evaluation of methods
Authors: Wiig H. , Reed R. K. , Aukland K.
Published: December 2017

Interstitial fluid pressure (IFP) was measured with two acute (micropipettes and wick-in-needle) and two chronic methods (perforated and porous capsules) in dog skin/subcutis. In control conditions all techniques gave similar mean pressures, approximately -2 mmHg. Overhydration induced by intravenous Ringer infusion, 10% of body wt, caused two to three times greater increase in pressure recorded with chronic than with acute methods but 2 h after the end of the infusion all methods gave similar pressures. An almost opposite pattern was observed during dehydration induced by peritoneal dialysis with hypertonic glucose. The fall in pressure recorded with the perforated capsule exceeded that of the porous capsule, both exceeding the pressure reduction measured with the acute methods by a factor of 2-5. The difference between pressures measured with both acute methods and the perforated capsule increased in the 90 min following dialysis. Acute overhydration or dehydration as well as aspiration from or infusion into perforated capsules caused a pressure gradient between lumen, capsule wall, and surrounding skin. We propose that the transient pressure differences recorded by acute vs. chronic methods during changes in hydration result from different physical properties of the capsule lining compared with that of the surrounding skin, in addition to a possible osmometer effect of the capsule lining.
Nonhuman primate model for regional wave travel and reflections along aortas
Authors: Latham R. D. , Rubal B. J. , Westerhof N. , Sipkema P. , Walsh R. A.
Published: December 2017

Arterial pulse transmission and wave reflections were studied in five mature anesthetized baboons (Papio anubis) using multisensor micromanometry. Simultaneous pressures were recorded from the left ventricle and every 10 cm along the aorta and its terminal branches, and flow velocity was measured in the aortic root. Aortic input impedance and regional foot-to-foot and apparent phase velocities were calculated. Aortography provided dimensional data for local reflection coefficients. Regional foot-to-foot wave speeds were somewhat lower than corresponding segments in humans. Proximal aortic pressure waveforms and characteristic impedance (110 +/- 29 dyn X s X cm-5) were not characteristic of middle-aged humans. Reflection coefficients at the terminal aortic bifurcation (0.06) at the level of the renal artery branches (0.09) were less than those found in humans. We conclude that the junction of the renal artery branches and the aorta in the baboon is closely matched and represents much less of a discrete reflection site than in humans. Although the baboon may be used to study pulse transmission characteristics in the baboon, this species is not a good model for the proximal systemic reflective characteristics of normal middle-aged humans.
Intramyocardial blood volume change in first moments of cardiac arrest in anesthetized goats
Authors: Vergroesen I. , Noble M. I. , Spaan J. A.
Published: December 2017

The effect of cardiac relaxation on the intramyocardial blood volume was studied by measuring the integrated difference between arterial inflow and great cardiac venous outflow. In nine anesthetized goats, the left main coronary artery was perfused under constant pressure. The great cardiac vein was drained under pressure control. The venous flow signal was amplified so that the integrated intramyocardial blood volume was constant in the beating heart. With normal vasomotor tone, the mean change in vascular volume was 3.01 +/- 0.18 (SE) ml/100 g left ventricle (LV); 67% of the volume change was achieved in 1.60 +/- 0.09 s. For the fully dilated bed (adenosine infusion), the values were 4.13 +/- 0.33 ml/100 g and 0.96 +/- 0.06 s, respectively. The volume change could be correlated with the venous pressure during cardiac arrest (Pvd) and the change in mean left ventricular pressure after cardiac arrest (r = 0.95). The correlation improved when data were selected for Pvd less than 6 mmHg to r = 0.98. We assumed that the change in vascular transmural pressure can be approximated as half the mean left ventricular pressure change. The intramyocardial vascular compliance was then estimated as 0.104 +/- 0.012 and 0.146 +/- 0.028 ml X mmHg-1 X 100 g-1 for control and adenosine conditions, respectively. The long time constants excluded the large epicardial veins as the site of volume change; they were much longer than the duration of diastole in the beating heart. We conclude that the intramyocardial vascular compartment is capable of volume expansion on the order of 20% of its normal volume when myocardial compression by ventricular systole is suspended.
Effects of alpha-adrenergic blockade on coronary autoregulation in dogs
Authors: Jones C. E. , Liang I. Y. , Gwirtz P. A.
Published: December 2017

In alpha-chloralose-anesthetized, open-chest dogs, left coronary blood flow and oxygen extraction were measured at perfusion pressures from 25 to 175 mmHg. Pressure-flow relationships were obtained before and after alpha-blockade with prazosin or alpha 2-blockade with yohimbine in the presence of beta-blockade with propranolol. The efficiency of flow autoregulation with increments in pressure was calculated as the closed-loop gain and as the slope of flow to pressure. In all animals the highest gain and the lowest slope were seen when pressure increased from 75 to 125 mmHg. In the prazosin group before alpha-blockade the gain with this pressure increase was 0.76 +/- 0.05, whereas in the yohimbine group before alpha-blockade this gain was 0.75 +/- 0.03. Prazosin reduced the gain within the pressure range of 75–125 mmHg by 41%, and this reduction was statistically significant (P less than 0.05). Prazosin also significantly increased the flow to pressure slope within this range. In addition, at all pressures greater than or equal to 50 mmHg, the level of coronary flow was significantly increased by prazosin. The increase in flow and the reduction in autoregulatory efficiency with prazosin were not attributable to an increase in myocardial oxygen consumption. Yohimbine had no effects on the level of coronary flow or on the autoregulatory efficiency. These data indicate that an alpha 1-adrenoceptor mediated coronary constriction modulates coronary autoregulation.