bluuebunny/crossref_metadata_2025 huggingface dataset:
Paradox of enhanced contractility in postischemic rat hearts with depressed function
Authors: Schouten V. J. , Los G. J. , Kuypers P. D. , Brinkman C. J. , Huysmans H. A.
Published: December 2017

Depressed function of postischemic hearts may be related to incomplete recovery of coronary perfusion. To circumvent this factor we studied the properties of papillary muscles under controlled extracellular conditions. First, recovery of function was measured in postischemic rat hearts. Next, a muscle was dissected and superfused in a bath. After 40 min of ischemia, recovery of cardiac output was generally zero. Muscles from this group were relaxed or showed small contractures. After 20-30 min of ischemia recovery of coronary flow and cardiac output was 50-100%, and the isolated muscles showed the following properties (compared with Langendorff-perfused controls): 1) increased force at normal or low [Ca2+]; 2) action potential and postextrasystolic potentiation were unchanged, which indicates that Ca2+ influx per beat was unchanged; 3) the decay of potentiation was slowed, indicating a reduced rate of Ca2+ extrusion via Na(+)-Ca2+ exchange. This implies intracellular Ca2+ accumulation and explains the increased force. Postischemic enhancement of contractility (isovolumic pressure) was demonstrated also in whole heart preparations. We conclude that mild injury by preceding ischemia leads to enhanced contractility (Ca2+ accumulation), advanced injury to local contractures, and finally to a general contracture (Ca2+ overload). Recovery of heart function and coronary flow probably depends on the number and size of local contractures.
N omega-nitro-L-arginine selectively inhibits vasodilator responses to acetylcholine and bradykinin in cats
Authors: Bellan J. A. , Minkes R. K. , McNamara D. B. , Kadowitz P. J.
Published: December 2017

The effects of N omega-nitro-L-arginine (nitroarginine), an inhibitor of endothelium-dependent relaxing factor (EDRF) production, on vascular tone and responses to vasodilator and vasoconstrictor agents were investigated in the hindquarters vascular bed of the cat. Under constant flow conditions, infusion of nitroarginine into the hindquarters vascular bed caused a significant increase in systemic arterial and hindquarters perfusion pressures. During infusion of nitroarginine, hindquarters vasodilator responses to acetylcholine and bradykinin were reduced significantly whereas vasodilator responses to isoproterenol, PGE1, nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate were not altered. Infusion of nitroarginine significantly enhanced vasoconstrictor responses to the thromboxane receptor agonist U 46619 and to phenylephrine. The results of these studies are consistent with the hypotheses that EDRF production may involve the formation of nitric oxide or a nitroso compound from L-arginine, and that EDRF production may play a role in the regulation of vascular tone and in the mediation of responses to the endothelium-dependent vasodilators, acetylcholine and bradykinin, in resistance vessels in the hindquarters. These data support the concept that EDRF is very likely an endogenous nitrovasodilator derived from L-arginine in the hindquarters vascular bed of the cat.
Myogenic response of isolated pressurized rabbit ear artery is independent of endothelium
Authors: MacPherson R. D. , McLeod L. J. , Rasiah R. L.
Published: December 2017

Central ear artery segments, removed from urethan-anesthetized rabbits, were used to assess whether distention activation was dependent on intact and functional endothelium (ENDO). Changes in external arterial diameter were measured with light-dependent diode array mounted above the vessel. After constriction with norepinephrine, slow increases in pressure from 60 to 80 or 100 mmHg performed over 120 s (pressure ramps) failed to initiate distention, but initial diameter was maintained. Rapidly applied (500 ms) pressure increases (pressure jumps) across same pressure ranges gave rise to initial distention and a myogenic response resulting in a return to almost initial diameter while new pressure was maintained for 120 s. Myogenic activity was measured from extent of recovery of vessel to its initial diameter during maintenance of pressure jumps or ramps. Rapid jumps and slow ramps were performed in presence of an intact ENDO and again after ENDO was removed by passage of intraluminal gas. With pressure jumps 60 to 80 mmHg, degree of recovery in ENDO-denuded vessels was 91.9% compared with 89.5% in ENDO intact vessels. For pressure jumps 60 to 100 mmHg, extent of recovery was 87.4 and 89.6%. During application of pressure ramps of 20 or 40 mmHg, vessel diameter did not increase by greater than 5%. There are no significant differences in these data, and we conclude that myogenic response in rabbit ear artery is mediated independently of endothelial-derived factors, irrespective of whether myogenic activation is induced by pressure jumps or ramps.
Effect of SRI 63-675 on hemodynamics and blood PAF levels during porcine endotoxemia
Authors: Dobrowsky R. T. , Voyksner R. D. , Olson N. C.
Published: December 2017

We evaluated the effect of SRI 63-675, a specific platelet-activating factor (PAF) receptor antagonist, on hemodynamics and PAF biosynthesis during 4 h of porcine endotoxemia. Hexadecyl PAF was extracted from blood, purified by normal-phase and reverse-phase high-performance liquid chromatography (RP-HPLC), and quantitated by stable isotope dilution and thermospray mass spectrometry. Infusion of either saline or SRI 63–675 alone caused no change in hexadecyl PAF concentrations. In contrast, endotoxin increased blood hexadecyl PAF concentrations from 1.5 +/- 0.1 ng/ml at 0 h (baseline) to a peak value of 8.3 +/- 1.9 ng/ml at 0.5 h of endotoxemia (P less than 0.05). Blood PAF levels gradually declined toward the baseline value after 0.5 h of endotoxemia. Because endotoxin did not modify plasma acetylhydrolase activity ex vivo, the increased hexadecyl PAF levels were probably secondary to increased PAF biosynthesis and not decreased biodegradation. Bioassay of RP-HPLC fractions that were derived from endotoxemic blood and that eluted at a retention time consistent with [3H]alkyl PAF caused aggregation of washed rabbit platelets that was inhibited by SRI 63–675. The PAF receptor antagonist blocked the 0.5 h endotoxin-induced increase in blood hexadecyl PAF concentration concomitant with blockade of thrombocytopenia. The endotoxin-induced pulmonary hypertension, decreased cardiac index, and increases in pulmonary vascular resistance and alveolar-arterial O2 gradient were attenuated by SRI 63–675. The data suggest that PAF-stimulated PAF biosynthesis may substantially contribute to blood hexadecyl PAF levels and cardiopulmonary dysfunction during the initial phase of endotoxemia.
Sympathetic nerve modulation of regional cerebral blood flow during asphyxia in newborn piglets
Authors: Goplerud J. M. , Wagerle L. C. , Delivoria-Papadopoulos M.
Published: December 2017

Regional cerebral blood flow (rCBF) during asphyxia suggests a reflex vasoconstrictor mechanism active principally in brain cortex. Present studies in newborn piglets investigate sympathetic modulation of the cerebrovasculature both during and after acute asphyxia. Unilateral superior cervical sympathetic ganglionectomy (SCSG) was performed in 13 newborn piglets, after which asphyxia was produced by discontinuing ventilation. In 8 animals, blood flow was measured during control and sequentially 1, 2, and 3 min after ventilation was stopped. In 5 piglets with unilateral SCSG, cortical flow decreased in the innervated hemisphere, -34 +/- 14% after 2 min, and -25 +/- 9% at 3 min of asphyxia compared with control (104 +/- 22 ml.min-1.100 g-1; mean +/- SE). In contrast, the sympathetically denervated hemisphere showed -13 +/- 17% at 2 min and +7 +/- 23% at 3 min, representing 45 +/- 6% and 30 +/- 9% left-right (L-R) flow differences, respectively. Bilateral SCSG (3 piglets) similarly attenuated the cortical CBF vasoconstrictor response to asphyxia, +6 +/- 21% at 2 min and -8 +/- 5% at 3 min. Significant innervated-denervated rCBF differences were present during asphyxia in cerebral gray (55% +/- 24), cerebral white (41% +/- 16), caudate (25% +/- 7), hippocampus (36% +/- 12), and choroid plexus (145% +/- 42), indicating sympathetic nerve modulation. Brain stem structures showed increasing rCBF throughout asphyxia and no L-R differences.(ABSTRACT TRUNCATED AT 250 WORDS)
Potent effects of AP3A and AP4A on coronary resistance and autacoid release of intact rabbit hearts
Authors: Pohl U. , Ogilvie A. , Lamontagne D. , Busse R.
Published: December 2017

We investigated effects of platelet-derived dinucleotides diadenosine 5',5"'-P1,P3-triphosphate (AP3A) and diadenosine 5',5"'-P1,P4-tetraphosphate (AP4A) on coronary vasculature. In isolated rabbit hearts, saline perfused at constant flow (36 +/- 3 ml/min), AP3A and AP4A induced dose-dependent decreases in coronary perfusion pressure. Dose-effect curves of AP3A [-log M mean effective concentration (EC50) 6.2 +/- 0.1] and AP4A (EC50 6.4 +/- 0.2) were identical and not significantly different from those of adenosine, ADP, and ATP (n = 4-8). There were, however, distinct differences between both dinucleotides: pretreatment with endothelium-derived relaxing factor (EDRF)-inhibitors oxyhemoglobin (6 microM, n = 6) and NG-nitro-L-arginine (30 microM, n = 6) significantly reduced AP4A-induced dilation by 44 and 42% but did not affect vasomotor effects of AP3A or of sodium nitroprusside, adenosine, ATP, and ADP. Concentration of the stable hydrolysis product of prostaglandin (PG)I2, 6-keto-PGF1 alpha, increased by 173 +/- 25% in coronary effluent (n = 23) during infusion of AP3A (1 microM). This increase was significantly higher than during infusion of equimolar concentrations of AP4A (38 +/- 10%), ATP (23 +/- 5%), adenosine (20 +/- 10%), or an equimolar combination of AMP and ADP (52 +/- 25%), the hydrolysis products of AP3A. Luminometric and high-performance liquid chromatography analysis showed a nearly complete (94 +/- 3%) degradation of ATP during passage through the coronary bed while significant amounts of AP3A (31 +/- 5%) and AP4A (33 +/- 6%) remained uncleaved.(ABSTRACT TRUNCATED AT 250 WORDS)
Myoglobin function and energy metabolism of isolated cardiac myocytes: effect of sodium nitrite
Authors: Doeller J. E. , Wittenberg B. A.
Published: December 2017

Inactivation of intracellular myoglobin by sodium nitrite or by carbon monoxide in isolated cardiac myocytes diminishes steady-state respiratory rate and phosphocreatine concentration (PCr) by approximately 25% at nonlimiting oxygen pressures; oxidative phosphorylation and glycolysis together are insufficient to maintain ATP, and PCr falls. At concentrations required to convert myoglobin to high-spin ferric myoglobin, nitrite does not affect the respiration of isolated aerobic heart mitochondria. The creatine phosphokinase-catalyzed equilibrium between PCr and ATP is not affected by nitrite. Myoglobin inactivation reduces PCr in cells in which glycolytic ATP production is blocked by iodoacetate. However, inhibition of electron transport by rotenone does block myoglobin-mediated oxygen uptake. These data suggest that functional myoglobin augments mitochondrial oxidative phosphorylation [myoglobin-mediated oxidative phosphorylation (30)]. Myoglobin itself does not cross mitochondrial membrane(s). At high oxygen pressures used here, myoglobin is everywhere saturated with oxygen, and facilitated oxygen diffusion vanishes. Oxidative phosphorylation must be augmented by some effector, such as NADH or a carrier of reducing or oxidizing equivalents that can transduce the effect of oxymyoglobin across the mitochondrial membrane(s).
Opposed responses of large and small coronary arteries to propranolol during exercise in dogs
Authors: Berdeaux A. , Drieu la Rochelle C. , Richard V. , Giudicelli J. F.
Published: December 2017

This study was carried out to determine the relative role of alpha- and beta-adrenoceptors at the level of large epicardial and small resistance coronary arteries when sympathetic tone is increased by exercise. The responses of left circumflex coronary diameter and blood flow were examined at rest and during treadmill exercise in seven chronically instrumented dogs during control conditions (saline) and after propranolol administration (1 mg/kg) either alone or in combination with phentolamine (1.5 mg/kg). In control conditions, graded treadmill exercise (5, 10, and 12 km/h) resulted in a progressive increase in coronary artery diameter and decrease in coronary vascular resistance. After propranolol, coronary vascular resistance slightly increased at rest and then progressively decreased during exercise. Surprisingly, coronary artery diameter significantly decreased at rest as well as throughout the exercise period. Phentolamine significantly reduced the propranolol-induced effects on coronary arterial diameter but did not restore the exercise-induced dilation of the large coronary arteries observed during control conditions. In addition, phentolamine prevented the propranolol-induced increase in coronary vascular resistance at rest and reinforced the exercise-induced decrease in coronary vascular resistance observed under propranolol. Thus beta-adrenoceptors are essential in the mediation of exercise-induced dilation of large coronary arteries. In contrast, activation of beta-adrenoceptors is only partially responsible for the decrease in coronary vascular resistance during exercise. Finally, constriction of large coronary arteries after propranolol is mainly explained by the unmasking of alpha-adrenergic tone at rest, but other mechanisms are involved during exercise.
Regional function, blood flow, and oxygen utilization relations in repetitively occluded-reperfused canine myocardium
Authors: Vinten-Johansen J. , Gayheart P. A. , Johnston W. E. , Julian J. S. , Cordell A. R.
Published: December 2017

Temporary coronary occlusion followed by reperfusion severely reduces contractile function in the involved segment. We tested whether an uncoupling exists between O2 utilization (MVO2) and systolic shortening in the ischemic-reperfused segment subjected to repetitive coronary occlusion and reperfusion. In 10 anesthetized open-chest dogs, left ventricular pressure and segment length (sonomicrometry) relations were measured in the left anterior descending (LAD, ischemic-reperfused) segment and circumflex coronary artery (nonischemic segment). Four 12-min LAD occlusions were each followed by 30 min reperfusion. MVO2 was determined in both segments by transmural blood flow (15 microns microspheres) and regional coronary arterial-venous O2 extraction after each occlusion-reperfusion period. The four occlusion-reperfusion periods did not produce necrosis by staining with triphenyltetrazolium chloride. LAD occlusion produced dyskinesis [control = 16 +/- 3.0% systolic shortening (SS) vs. -8.8 +/- 1.5%, P less than 0.0001]. The first reperfusion restored SS only to 2.3 +/- 2.0%, which progressively deteriorated to -3.9 +/- 1.1% (P less than 0.05) with subsequent occlusion-reperfusion episodes. Relative to the nonischemic segment, MVO2 in the ischemic-reperfused segment decreased by only 18% despite dyskinesis. Pressure-length analysis showed systolic stiffening during reperfusion with displacement of the passive ischemic pressure-length loop to the left. Segment work (integral of each loop) continued to be generated at 34.5% of control levels after the last occlusion-reperfusion event in contrast to the negative SS. We conclude that 1) MVO2 in the ischemic-reperfused segment without necrosis remains elevated despite severe reductions in systolic shortening, and 2) the discrepancy between systolic shortening and MVO2 is partially due to persistent development of segment work.
Influence of systolic pressure profile on rate of left ventricular pressure fall
Authors: Gillebert T. C. , Lew W. Y.
Published: December 2017

We examined the influence of the systolic left ventricular pressure (LVP) waveform on the rate of isovolumetric LVP fall, as assessed by the time constant tau. Seven open-chest dogs were instrumented with a micromanometer in the left ventricle, with segment length gauges in the anterior and posterior midwall of the left ventricle, and with a balloon-tipped catheter in the proximal aorta. The intra-aortic balloon was inflated before the onset of ejection (early) or during midejection (late) to produce timed and graded increases in peak LVP of 2-20 mmHg. The rate of LVP fall slowed significantly more with late than with early increases in LVP (tau increased 1.5 +/- 0.5 vs. 0.5 +/- 0.3%/mmHg increase in peak LVP, respectively, P less than 0.001). For a similar increase in peak LVP, there was a progressively greater increase in tau when the timing of balloon inflation was progressively delayed from early to late ejection (in 10-ms increments). The differential effect of early vs. late pressure increases on tau was not related to regional differences in segment length behavior nor to an increase in regional nonuniformity between anterior and posterior sites. We conclude that under the experimental conditions of an intact, ejecting left ventricle, the systolic pressure profile is an important determinant of the rate of pressure fall. The rate of LVP fall slows in direct proportion to the magnitude of increase in systolic pressure. The sensitivity to systolic load increases progressively throughout the ejection period, so that the rate of LVP fall slows significantly more with late than with early pressure increases.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of ATP-dependent surfactant secretion and activation of second-messenger systems in alveolar type II cells
Authors: Voyno-Yasenetskaya T. A. , Dobbs L. G. , Williams M. C.
Published: December 2017

Several different classes of agonists are known to stimulate exocytosis in type II cells. These agonists cause increases in second messengers, such as adenosine 3',5'-cyclic monophosphate (cAMP) or cytosolic Ca2+, and/or stimulate protein kinase C. We studied generation of cAMP and phosphoinositide (PI) turnover in monolayer cultures of type II cells and measured [Ca2+]i in single cultured cells. ATP [10–4 M], which stimulates secretion of phosphatidylcholine (PC) and increases cellular cAMP, also stimulated PI turnover and increased [Ca2+]i. 12-O-tetradecanoylphorbol-13-acetate (TPA), which stimulates PC secretion and activates protein kinase C, did not increase [Ca2+]i. Pretreatment of type II cells with the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) inhibited the PC secretion induced by ATP and TPA and blocked the increase in PI turnover caused by ATP. ATP-dependent surfactant secretion and stimulation of PI turnover could also be inhibited by pretreatment of the cells with pertussis toxin. We used the fluorescent probe indo-1 to measure [Ca2+]i in single cultured type II cells. ATP produced rapid transient increases in [Ca2+]i, which could be prevented by pretreatment of the cells with either TPA or W-7. Our data suggest that pertussis toxin-sensitive G protein(s) are involved in ATP-dependent activation of PI turnover and in secretion of surfactant in type II cells. Activation of protein kinase C blocks the ATP-stimulated increase in [Ca2+]i. Finally, calmodulin may be involved in the regulation of ATP-dependent increase in [Ca2+]i, the activation of PI turnover, and the secretion of surfactant in type II cells.

lung; exocytosis; cell calcium; G proteins; phosphoinositide turnover
Time course of mechanical efficiency during afterloaded contractions in isolated cardiac muscle
Authors: Peterson Jon N. , Alpert Norman R.
Published: December 2017

The time course of mechanical efficiency during working contractions in rabbit papillary muscle is presented. Efficiency is found to remain relatively constant during the working portion of the twitch, when the muscle is contracting against a constant load. As afterload was decreased, efficiency increased to 65 ± 11% (mean ± SE, n = 3) at 10% developed force at maximum length. This is in contrast to muscle work, which reached a peak of 3.0 ± 0.3 ( n = 6) mJ/g at 50% developed force at maximum length.

heart; initial heat; rabbit; working contractions
Response of canine coronary collateral vessels to ergonovine and alpha-adrenergic stimulation
Authors: Bache R. J. , Foreman B. , Hautamaa P. V.
Published: December 2017

The ability of moderately well-developed coronary collateral vessels to undergo vasoconstriction in response to alpha-adrenergic stimulation and to ergonovine was studied. Studies were performed in 15 dogs 4-16 wk after embolic occlusion of the left anterior descending coronary artery had been performed to stimulate collateral vessel growth. Interarterial collateral flow was measured as retrograde flow from the cannulated left anterior descending coronary artery, while microvascular collateral flow was measured as continuing tissue flow determined with radioactive microspheres administered during the retrograde flow collection. Studies were performed after beta-adrenergic blockade with propranolol. Neither cardiac sympathetic nerve stimulation nor alpha 1-adrenergic stimulation with phenylephrine caused significant change in retrograde blood flow or myocardial tissue flow. The selective alpha 2-adrenergic agonist, B-HT 933, decreased tissue flow in the collateral-dependent region but did not significantly alter retrograde flow. Although these data indicate that intramural microvascular collateral communications are capable of vasoconstriction in response to alpha 2-adrenergic stimulation, the larger interarterial collaterals are unresponsive to alpha-adrenergic influences. However, under the conditions of the experiment, adrenergic activity did not appear to influence collateral function, since neither alpha 1-adrenergic blockade with prazosin nor alpha 2-adrenergic blockade with rauwolscine altered collateral flow. Ergonovine, 0.2-0.8 microgram.kg-1.min-1, caused a 22 +/- 4% decrease in retrograde flow (P less than 0.01) but did not alter microvascular collateral flow. Thus, of the agents tested, only ergonovine caused vasoconstriction of the large interarterial coronary collateral vessels.
Regulation of atrial autonomic receptors in experimental cyanotic heart disease
Authors: Doshi R. , Strandness E. , Bernstein D.
Published: December 2017

During chronic hypoxemia, left ventricular beta-adrenergic receptor density is decreased and a dissociation occurs between increased chronotropic and decreased inotropic responses to chronically elevated sympathetic tone. To determine whether this dissociation was related to alterations in autonomic receptor populations in the right atrium, we studied right atrial cholinergic and beta-adrenergic receptors in chronically hypoxemic newborn lambs and in normoxemic controls. Heart rate response was determined by infusing isoproterenol at 0.1 or 0.5 microgram.kg-1.min-1. Muscarinic receptors were quantified with [3H]quinuclidinyl benzilate and beta-adrenergic receptors with [125I]iodocyanopindolol. Competition with ICI 118,551 was used to determine beta 1- vs. beta 2-receptor subtypes. In the hypoxemic lambs, isoproterenol resulted in a lesser percentage increase in heart rate (hypoxemic, 46 +/- 6% vs. control, 89 +/- 17%, P less than 0.05); however, because baseline heart rate was higher in the hypoxemic lambs (213 +/- 7 vs. 177 +/- 12 beats/min, P less than 0.05), maximal heart rate responses were similar (310 +/- 7 vs. 326 +/- 6 beats/min, NS). There was no change in receptor density or affinity of either muscarinic or beta-adrenergic receptors and no change in the proportion of beta 1- vs. beta 2-receptor subtypes. Thus the dissociation between the chronotropic and inotropic responses to chronic hypoxemia may be in part secondary to a differential regulation of beta-adrenergic receptors between the left ventricle and the right atrium.
Circulatory changes following premature delivery in a baboon model of hyaline membrane disease
Authors: Kinsella J. P. , Gerstmann D. R. , Delemos R. A.
Published: December 2017

The premature baboon delivered by hysterotomy at 140 +/- 2 days (75%) gestation develops hyaline membrane disease (HMD) and left-to-right (L-R) shunting through the patent ductus arteriosus (PDA). To characterize hemodynamic changes that follow premature delivery, we measured systemic and organ blood flow, oxygen transport, and systemic vascular resistance over the first 96 h of life. We compared these measurements with those from more mature animals of the same species. Radiolabeled microspheres were used to measure organ blood flow (in ml.min-1.g-1) at 3 (n = 18), 23 (n = 17), and 96 h (n = 4) in the premature animals, and at 13 +/- 4 mo in the older animals (n = 5). Premature animals demonstrated over the first 96 h of life significant hemodynamic changes that included decreased systemic vascular resistance (P less than 0.001), increased systemic (P less than 0.05), intestinal (P less than 0.05), and hepatic blood flow (P less than 0.05), as well as resolution of L-R PDA shunting. These 96-h values were similar to those of the more mature infant baboons. Blood flow and oxygen transport to the kidneys and cerebrum did not significantly increase over the first 96 h in premature baboons and were significantly less than those of 13-mo-old animals (P less than 0.01, both). We speculate that low renal and cerebral blood flow in the 140-day premature baboon are manifestations of multisystem immaturity and, as such, may represent persistent physiological disturbances that are distinct from the severity of underlying lung disease in HMD.
Modeling the dynamic interaction between left ventricle and intra-aortic balloon pump
Authors: Sun Y.
Published: December 2017

An analog model is developed to characterize how alterations of some intra-aortic balloon pump (IABP) parameters affect the coupling between left ventricle (LV) and aorta. The time-varying elastance concept is applied to modeling both active components (LV and IABP) in the assisted circulation. Pressure and flow waveforms in the system are determined by numerically integrating five simultaneous state equations that represent the system dynamics. Validity of the model is supported by good agreement between model predictions and published data on LV pressure-volume (P-V) loops, end-systolic P-V relations, and hemodynamic consequences of adjusting IABP timing and speed. The model also predicts that increasing balloon volume increases the diastolic aortic pressure augmentation but has a negative effect of increasing LV load. Increasing balloon diameter over length ratio and holding a constant volume increases the diastolic augmentation and decreases the LV demand. Positioning the balloon closer to the heart improves systolic unloading but affects neither diastolic augmentation nor cardiac output. These results suggest that occlusivity is a major determinant of IABP effectiveness and plays a more important role than balloon volume and position.
Effect of dietary magnesium on atrial natriuretic peptide release
Authors: Wong N. L. , Hu D. C. , Wong E. F.
Published: December 2017

Magnesium is the second most abundant divalent ion in the body, but the effects of this cation on atrial natriuretic peptide (ANP) release have not been examined. The present study was conducted to determine the effect of magnesium on ANP secretion. Experiments were conducted in six groups of male Wistar rats. Each group was assigned a diet containing a different amount of magnesium. Plasma magnesium was 0.42 +/- 0.01, 0.63 +/- 0.01, 0.75 +/- 0.02, 0.97 +/- 0.03, 1.03 +/- 0.01, and 1.19 +/- 0.01 mM in groups I, II, III, IV, V, and VI, respectively. Plasma ANP concentration was significantly higher in the hypermagnesemic animals and significantly lower in the hypomagnesemic rats. A significant positive correlation was found between plasma magnesium and plasma ANP levels (y = 88 + 23 chi; r = 0.46; P less than 0.01). ANP concentration in the atria was lower in hypomagnesemic rats and higher in hypermagnesemic rats. This suggests that the low concentrations of ANP found in the plasma of hypomagnesemic animals were due to the lack of ANP in the atria. The atria from the various groups were isolated and perfused in a modified Langendorff apparatus to measure the rate of ANP secretion. Our results showed that the hypomagnesemic rats have a lower release rate as opposed to that seen in hypermagnesemic animals. A significant correlation was also seen between ANP secretion and tissue ANP concentration. The higher rate of ANP release from the heart of hypermagnesemic animals was due to the presence of more ANP, which was reduced during hypomagnesemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Dilation and constriction of large coronary arteries in conscious dogs by endothelin
Authors: Wang J. , Zeballos G. A. , Kaley G. , Hintze T. H.
Published: December 2017

This study examined the effects of endothelin on coronary circulation and the relationship between the plasma concentration of endothelin and cardiovascular function in conscious dogs. The injection of a low dose (50 ng/kg) of endothelin increased coronary artery diameter by 2.17 +/- 0.49% and then decreased coronary artery diameter by 1.13 +/- 0.17% (P less than 0.01) from 3.51 +/- 0.14 mm. This dose increased coronary blood flow by 39 +/- 8.5% and then decreased coronary blood flow by 14 +/- 3.5% (P less than 0.01) from 25 +/- 1.6 ml/min, respectively. Four doses of endothelin (1, 10, 20, and 50 ng.kg-1.min-1) were infused for 20 min each as a cumulative dose response and blood samples were taken to assay endothelin. Significant changes in systemic and coronary dynamics were observed at infusions of 10 and 20 ng.kg-1.min-1. For instance, at 10 ng.kg-1.min-1 there was a significant (P less than 0.05) increase in mean arterial pressure (10 +/- 2.7%), left ventricular (LV) end-diastolic (32 +/- 11%), and LV systolic (8 +/- 3%) pressures and late diastolic coronary resistance (12 +/- 3.0%). This was accompanied by a reduction in large coronary artery diameter (2.0 +/- 0.5%) and coronary blood flow (22 +/- 6.0%; P less than 0.05). At this infusion rate, plasma endothelin reached 70 pg/ml when compared with a control value of 4 +/- 1 pg/ml. Thus the bolus injections of endothelin evoked a biphasic response of large and small coronary arteries, whereas during infusion we observed only vasoconstriction. The levels of circulating endothelin necessary to cause significant cardiovascular effects are much higher than expected.
A new model for studying ischemia-reperfusion injury in hamster cheek pouch
Authors: Yasuhara H. , Hobson R. W. , Dillon P. K. , Duran W. N.
Published: December 2017

The cheek pouch was prepared as a single layer and attached to a two-piece Lucite chamber that was filled with bicarbonate buffer (pH 7.35, equilibrated with 95% N2-5% CO2). Two microcirculatory areas were circumscribed in the cheek pouch by equilateral triangular chambers. Each chamber was made of 90-microns thick Mylar sheet (2 mm wide, 18 mm long). A cover slip was used as the chamber top. Ischemia was induced by applying pressure to the cover slip. The experimental area was reperfused after 1 h of ischemia by releasing the pressure. The other area served as control. One hour of reperfusion after 1 h of ischemia caused a significant increase in the number of leukocytes adhering to postcapillary venules (PCVs) per 100 microns vessel length in the ischemic area relative to the values in the control area (7.8 +/- 2.5 vs. 3.7 +/- 1.3, respectively, for PCVs 10-19.9 microns diam; and 10.9 +/- 2.8 vs. 6.2 +/- 1.8 for PCVs 20-29.9 microns diam; P less than 0.01 for both comparisons). The results demonstrate the adequacy of the model to investigate leukocyte adhesion to endothelium in ischemia-reperfusion. Because blood flow is maintained in most of the pouch, our model should also be useful for identifying possible interactions between ischemic and nonischemic areas in the microcirculation.
Caffeine-induced block of Na+ current in guinea pig single ventricular cells
Authors: Habuchi Y. , Tanaka H. , Furukawa T. , Tsujimura Y.
Published: December 2017

Effects of caffeine on Na+ current (INa) were investigated in single ventricular cells from guinea pigs using the whole cell clamp method. With a Ca(2+)-containing internal solution (pCa 8.2), 10 mM caffeine blocked INa by 17.5 +/- 4.6% at a -120-mV holding potential. It was accompanied by 3- to 5-mV shifts of the steady-state inactivation curve and time constant-voltage relationship toward hyperpolarization. The inactivation kinetics spontaneously shifted toward hyperpolarization at 0.30 +/- 0.17 mV/min. The spontaneous shift was accompanied by a similar negative shift of the threshold potential, whereas caffeine did not affect it. Caffeine retarded the recovery of INa from inactivation, and a 4-mV positive shift in the recovery potential produced a similar retardation in INa recovery without caffeine. The INa block by caffeine was not influenced by reinforcing the internal buffering capacities using internal solutions containing 40 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid or 50 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid or by pretreating the cell with 1 microM ryanodine. Neither pretreatment with isoproterenol or H 7 nor prestimulation of Gs protein by nonhydrolyzable GTP (GTP gamma S) altered the effects of caffeine on INa. It is concluded that caffeine inhibits INa and shifts the inactivation kinetics without being mediated by changes in intracellular ionic composition or intracellular signaling systems. Direct action on the channel proteins may be involved.
Effect of cyclocreatine feeding on levels of amino acids in rat hearts before and after an ischemic episode
Authors: Osbakken M. , Zhang D. N. , Nelson D. , Erecinska M.
Published: December 2017

Feeding Sprague-Dawley rats for 3 wk a diet containing 1% by weight of cyclocreatine increased the reservoir of the high-energy phosphate compounds but also caused alterations in the levels of the two key amino acids, aspartate and glutamate. Both were decreased by approximately 50% in the presence of an unaltered content of glutamine. In vitro exposure of these hearts to sequential perfusion, global ischemia, and reperfusion in the absence of added amino acids resulted in changes in aspartate, glutamate, and glutamine that were different from those in hearts from control rats. In the cyclocreatine-fed group, aspartate concentration ([aspartate]) and [glutamate] fell after global ischemia, whereas [glutamine] was unaltered. [Glutamine] decreased, however, in the reperfusion period. In control hearts, the predominant effect was a steady decline in glutamine, which was accompanied by either less than 10% (after global ischemia) or 30-50% fall (after reperfusion) in [aspartate] and [glutamate]. The concentration of tissue Pi was smaller in hearts from cyclocreatine-fed rats and appeared to increase more slowly during ischemia. In the presence of rotenone and aminooxyacetate, heart homogenates catalyzed production of glutamate from glutamine, which was markedly stimulated by Pi and inhibited by H+. It is postulated that 1) phosphate-activated glutaminase is an important enzyme that determines cardiac [glutamate], 2) lower [phosphate] in hearts from rats fed cyclocreatine is responsible for the apparently lesser activity of glutaminase, 3) breakdown of the high-energy phosphate compounds and consequent rise in Pi activates glutaminase, and 4) slow breakdown of glutamine during global ischemia is a result of inhibition of glutaminase by H+.
A model of beta-adrenergic effects on calcium and potassium current in bullfrog atrial myocytes
Authors: Shumaker J. M. , Clark J. W. , Giles W. R.
Published: December 2017

A model of beta-adrenergic and muscarinic cholinergic effects on the bullfrog atrial myocyte has been developed to simulate the dose-dependent effects of isoprenaline (Iso) on the action potential duration (APD); i.e., low doses of Iso lengthen the APD, whereas high doses shorten the APD. In this model, the reduction in APD is the result of 1) calcium-dependent inactivation of calcium current (ICa) resulting from the enhancement of ICa by Iso and 2) an enhancement of potassium current (IK) due to both an Iso-induced increase in the rate of activation of IK and an increase in peak action potential height. The effect of acetylcholine (ACh) is simulated by a reduction in the Iso-induced increase in ICa and IK through a reduction in relative adenosine 3',5'-cyclic monophosphate concentration ([cAMP]), as well as activation of the ACh-sensitive potassium current. At low [Iso] levels in the presence of a high [ACh], the muscarinic cholinergic effects dominate the beta-adrenergic change. However, for a large [Iso] and a small [ACh], this pattern of changes in transmembrane currents is different; in this case the model predicts that ACh can actually increase APD.
Newborn cardiorenal dynamics: a state of atrial natriuretic peptide unresponsiveness
Authors: Silberbach M. , Stejskal E. , Foker J. , Bianco R. , Tobian L. , Burnett J. C. , Einzig S.
Published: December 2017

The newborn has an attenuated response to saline fluid challenge. We studied the response of endogenous atrial natriuretic peptides (ANF) to 10% body weight graded isotonic saline volume expansion (VE) in 14 anesthetized neonatal lambs which were either 1 day old or 7 days old. Plasma ANF values were unchanged at 3.3% and 10% VE compared with control values (56 +/- 28 vs. 66 +/- 17 and 66 +/- 37 pg/ml, not significant) in the 1-day-old lambs, whereas values increased significantly at both 3.3% and 10% VE (47 +/- 40 vs. 99 +/- 57 and 96 +/- 73, P = 0.022 and P = 0.018, respectively) in the 7-day-old lambs. No relationship existed between right atrial (RAP) or pulmonary capillary wedge pressures (PCWP) and plasma ANF in the 1-day-old lambs; however, a significant correlation existed (RAP, P = 0.015; PCWP, P = 0.022) in the 7-day-old lambs. In general, renal function was improved in the 7-day-old lambs compared with the 1-day-old lambs, but only changes in fractional sodium excretion were significantly different (P = 0.017). We speculate that ANF unresponsiveness in the 1-day-old lamb is related to physiological transitions during the birth process and that the maturation of the renal response to VE may require maturation of the atrial mechanism which permits ANF secretion.
Lack of coupling between adrenal cortical metabolic activity and blood flow in anesthetized dogs
Authors: Sakima N. T. , Breslow M. J. , Raff H. , Traystman R. J.
Published: December 2017

Pages H410–H415: N. T. Sakima, M. J. Breslow, H. Raff, and R. J. Traystman. “Lack of coupling between adrenal cortical metabolic activity and blood flow in anesthetized dogs.” Page H412: The units for oxygen consumption in Fig. 3 should read as cc O2/min/100 g adrenal gland.
Hemodynamic responses evoked by endothelin from central cardiovascular neural substrates
Authors: Hashim M. A. , Tadepalli A. S.
Published: December 2017

Endothelin-1 (ET-1, 3-10 pmol) applied to the fourth cerebral ventricle of anesthetized ventilated rats decreased mean arterial pressure (MAP, 37 +/- 5 to 55 +/- 5%), heart rate (13 +/- 7 to 21 +/- 3%), and renal blood flow (RBF, 41 +/- 7 to 45 +/- 8%; all values are means +/- SE) for 30-90 min. At a 30-pmol dose of ET-1, the decrease in MAP was preceded by an increase (58 +/- 16%). Micropneumophoresis of ET-1 (100-300 fmol) into discrete glutamate-responsive cardiovascular loci within the nucleus tractus solitarii (NTS), viz., the dorsal strip and the commissural subnucleus, produced depressor and bradycardic responses. However, central ET-1 was ineffective in evoking swallowing responses when microinjected into glutamate-responsive deglutitive sites in the NTS. These data suggest that, at low doses, ET-1 evokes hypotension and bradycardia by a specific neuronal action in the central nervous system; one site of action appears to be the cardiovascular neural substrates within the NTS; decreases in RBF may be secondary to the hypotension, since renal vascular resistance also decreased. In anesthetized nonventilated rats, ET-1 (3 and 10 pmol) applied to the fourth ventricle produced profound respiratory depression accompanied by a transient pressor effect. Thus centrally administered ET-1 can elicit complex cardiovascular responses by a direct action on cardiovascular substrates and/or indirectly via respiratory depression.
Beta 2-adrenoceptor-mediated positive dromotropic effects on atrioventricular node of dogs
Authors: Motomura S. , Hashimoto K.
Published: December 2017

The functional significance of beta 2-adrenoceptors in atrioventricular (AV) nodal conduction was investigated by using canine isolated blood-perfused AV node preparations. Dose-dependent shortening of the atrio-His bundle (A-H) interval by dl-procaterol hydrochloride hemihydrate (0.03-1 nmol) injected intra-arterially into the AV node artery was affected little by an infusion of dl-atenolol (10 nmol/min) into the same artery, whereas the dose-response curve for the positive dromotropic effect of procaterol was shifted markedly to the right by approximately 1.5 and 2.5 log units with ICI 118551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylamino-bu tan-2-ol]- hydrochloride (1 and 10 nmol/min). The positive dromotropic effect of dl-T-1583 [alpha-(3,4,5-trimethoxyphenethylaminomethyl)-3,4-dihydroxybenzyl- alcohol] hydrochloride (30-300 pmol), a selective beta 1-adrenoceptor agonist, was shifted to the right by approximately 1.2 log units with dl-atenolol (10 nmol/min) but was affected little by ICI 118551 (10 nmol/min). The dose-response curve for l-isoproterenol hydrochloride (3-100 pmol) was shifted to the right by 0.7 log unit with ICI 118551 (10 nmol/min) and by 1.7 log units with atenolol (10 nmol/min). The dose-response curve for dl-norepinephrine (0.03-1 nmol) was shifted to the right by 1.0 log unit with atenolol only, whereas the curve for l-epinephrine (0.03-1 nmol) was shifted by 0.45 log unit with ICI 118551 (10 nmol/min). These results suggest that both beta 1- and beta 2-adrenoceptors, which coexist on the AV node, play a functional role in AV nodal conduction.
Adaptation to sodium restriction in renin-immunized spontaneously hypertensive and normotensive rats
Authors: Jover B. , Michel J. B. , Dupont M. , Corvol P. , Mimran A.
Published: December 2017

The influence of active immunization against renin on the systemic and renal adaptation to abrupt suppression of dietary sodium was assessed in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Very low level of plasma renin activity and no response of circulating renin to sodium restriction were observed in immunized rats. The final systolic arterial pressure achieved in immunized SHR (144 +/- 3 mmHg) was similar to that observed in nonimmunized WKY (137 +/- 4 mmHg), and no influence of renin immunization on renal blood flow was observed in both strains maintained on ad libitum sodium intake. Dietary sodium restriction was associated with a consistent decrease in arterial pressure in immunized rats, whereas no change occurred in sham-immunized rats. No impairment in the renal adaptation was detected in immunized rats (6-day cumulative sodium excretion of 1.67 +/- 0.2 and 1.65 +/- 0.3 mmol in immunized SHR and WKY, respectively, and 1.50 +/- 0.2 and 1.21 +/- 0.2 mmol in sham-immunized SHR and WKY rats). These studies indicate that renin immunization decreases arterial pressure but does not affect renal adaptation to dietary sodium restriction in hypertensive and normotensive rats.
ANF does not increase total body venous compliance in conscious rats with myocardial infarction
Authors: Chien Y. , Pegram B. L. , Kardon M. B. , Frohlich E. D.
Published: December 2017

To test the hypothesis that atrial natriuretic factor (ANF) increases total body venous compliance through venodilation and thereby reduces cardiac preload, we compared the systemic hemodynamic effects of ANF (99-126) with the venodilator nitroglycerin in conscious rats with myocardial infarction (mean infarct size 25%) induced by coronary artery ligation 3 wk previously. A 30-min ANF infusion (0.5 microgram.kg-1.min-1) decreased mean arterial pressure, central venous pressure, and blood volume by 11 mmHg, 0.8 mmHg, and 3 ml/kg, respectively (P less than 0.02). Nitroglycerin (10 micrograms.kg-1.min-1) similarly reduced arterial and venous pressures (7 and 0.6 mmHg; P less than 0.02) but increased blood volume by 2 ml/kg (P less than 0.05). Both ANF and nitroglycerin reduced mean circulatory filling pressure (MCFP) by 1 mmHg (P less than 0.05). Compared with vehicle infusion, nitroglycerin increased total body vascular compliance as derived from serial MCFP measurements taken during 10% blood volume changes (2.09 +/- 0.12 vs. 2.76 +/- 0.32 ml.kg-1.mmHg-1; P less than 0.05) and reduced extrapolated unstressed volume (34.96 +/- 1.10 vs. 23.79 +/- 3.80 ml/kg; P less than 0.02). In contrast, ANF had no effect on either measurement. These data suggest that ANF and nitroglycerin reduced cardiac filling pressure through different mechanisms; the lack of effects of ANF on total body venous compliance and unstressed volume does not support its venodilating effect in these rats postmyocardial infarction.
Adrenergic activation of glycogen phosphorylase in primary culture diabetic cardiomyocytes
Authors: Buczek-Thomas J. A. , Jaspers S. R. , Miller T. B.
Published: December 2017

The basis of catecholamine-induced activation of glycogen phosphorylase was investigated in adult rat cardiomyocytes isolated from normal and alloxan-diabetic animals. Cells derived from diabetic animals exhibited a hypersensitive response to epinephrine stimulation that was apparent 3 h after cell isolation and was further enhanced on maintenance of the myocytes in culture for 24 h. Normal cells initially lacked the hypersensitive response to epinephrine stimulation, although on maintenance of these cells in culture for 24 h, the hypersensitive response was acquired in vitro. To assess alpha- and beta-adrenergic mediation of the response, normal and diabetic cardiomyocytes were incubated with propranolol, a beta-blocker, before direct alpha 1-receptor stimulation with phenylephrine. Both normal and diabetic myocytes failed to undergo activation of phosphorylase in 3- or 24-h cell cultures. In addition, the effects of epinephrine on phosphorylase activation were completely inhibited by propranolol, whereas prazosin, an alpha-blocker, was unsuccessful. The present data suggest that the hypersensitive response of glycogen phosphorylase in normal and diabetic cardiomyocytes is solely mediated through beta-adrenergic receptor activation.