Circulation research
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Circulation research · Sep 1990
Comparative StudyAcute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs.
To understand the cardiovascular response to respiratory acidosis, we measured hemodynamics, left ventricular pressure, and left ventricular volume (three ultrasonic crystal pairs) during eucapnia and respiratory acidosis in 10 fentanyl-anesthetized open-chest dogs. Left ventricular contractility was assessed primarily by measuring the slope (Emax) and intercept (V0) of the left ventricular end-systolic pressure-volume relation determined by combining end-systolic points from a vena caval occlusion and from brief aortic cross-clamping. Respiratory acidosis (pH 7.09, Pco2 92 mm Hg) reduced contractility by a decrease in Emax (11.4 to 9.2 mm Hg/ml, p less than 0.01) with no change in V0. ⋯ We conclude that the effect of respiratory acidosis on the circulation is to increase venous return (equals cardiac output) in the face of decreased left ventricular contractility. The beta-adrenergic response to respiratory acidosis substantially ameliorated the increase in end-systolic volume and supported the increase in venous return but did not alter the associated tachycardia or vasodilation. Respiratory acidosis, like propranolol treatment, decreases contractility by decreasing Emax.
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Circulation research · Aug 1990
H(+)-induced vasodilation of rat aorta is mediated by alterations in intracellular calcium sequestration.
Acidosis induces vasodilation both in vivo and in vitro. Although it is commonly surmised that acidosis alters contractility by affecting contractile proteins and calcium entry, the exact role of these mechanisms in acidosis-induced vasodilation has not been determined. In the present study, we demonstrated that a novel mechanism, involving increased calcium sequestration into intracellular sites sensitive to norepinephrine, mediates the vasodilation associated with relatively modest decreases in pH. ⋯ These effects of acidification were shown to be associated with an increase in the amount of calcium sequestered into the norepinephrine-sensitive intracellular calcium store. These findings clearly indicate that acidification, within a range that has no effect on other aspects of smooth muscle activation, elicits vasodilation by stimulating intracellular calcium sequestration. This action may represent a predominant mechanism whereby acidosis alters vascular smooth muscle contractility.
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Circulation research · Apr 1990
Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode.
We have shown previously that preconditioning myocardium with four 5-minute episodes of ischemia and reperfusion dramatically limited the size of infarcts caused by a subsequent 40-minute episode of sustained ischemia. The current study was undertaken to assess whether the same preconditioning protocol slowed the loss of high energy phosphates, limited catabolite accumulation, and/or delayed ultrastructural damage during a sustained ischemic episode. Myocardial metabolites and ultrastructure in the severely ischemic subendocardial regions were compared between control and preconditioned canine hearts. ⋯ Accumulation of glucose-1-phosphate, glucose-6-phosphate, and lactate also was reduced markedly by preconditioning, due to reduced rates of glycogen breakdown and and anaerobic glycolysis. We propose that preconditioning reduces myocardial energy demand during ischemia, which results in a reduced rate of high energy phosphate utilization and a reduced rate of anaerobic glycolysis. Either preservation of ATP or reduction of the cellular load of catabolites may be responsible for delaying ischemic cell death.
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Circulation research · Mar 1990
Comparative StudyImportance of endogenous angiotensin II in the cardiovascular responses to sympathetic stimulation in conscious rabbits.
Pharmacological evidence indicates that angiotensin (Ang II) converting enzyme inhibitors attenuate cardiovascular responses to sympathetic stimulation. To investigate the physiological significance of this attenuation, the pressor and heart rate responses to bilateral carotid occlusion (BCO) were studied before and after administration of captopril and again during Ang II replacement in conscious, aortic nerve-sectioned rabbits with chronically implanted carotid occluders. In the control period, BCO produced increases (p less than 0.05) in mean arterial pressure (MAP) and heart rate (HR) of 37.3 +/- 3.0 mm Hg and 21.7 +/- 5.4 beats/min from baseline values of 79.1 +/- 2.5 mm Hg and 255.4 +/- 16.7 beats/min. ⋯ The response was reduced by less than 40%, indicating only a modest postsynaptic component to the action of captopril. These results provide physiological evidence for an important action of endogenous Ang II in facilitating the cardiovascular responses to sympathetic stimulation in conscious rabbits. This facilitation is not due to an action upon the baroreflex per se but results, at least in part, from a presynaptic action of Ang II.
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Circulation research · Jan 1990
Comparative StudyImpact of carbon monoxide on cardiopulmonary dysfunction after smoke inhalation injury.
With the inhalation of smoke, there are both cardiopulmonary changes and elevated levels of carbon monoxide (CO). We hypothesize that these changes in cardiopulmonary function are the result of a histotoxic hypoxia associated with CO poisoning. This hypothesis was tested in chronically instrumented sheep (n = 19). ⋯ In the control and CO group, neither lung lymph flow nor maximum elastance varied from the baseline value. We conclude that the cardiopulmonary dysfunction after smoke inhalation does not occur after a similar exposure to CO. Initial CO poisoning alone is not a causative factor of cardiopulmonary dysfunction after smoke inhalation.