ABSTRACT
In isolated rabbit hearts perfused with suspension of red blood cells, we investigated the role of the endothelium and of several substances in the coronary vasoconstriction induced by a high arterial blood oxygen tension (PaO2). Red blood cells in Krebs-Henseleit buffer were oxygenated to obtain control and high-PaO2 perfusates. Arterial oxygen content was kept constant in both perfusates by reducing hemoglobin concentration in the high-PaO2 perfusate. Coronary blood flow was kept constant so that oxygen supply would not vary with the rise in PaO2. Increases in perfusion pressure therefore reflected increased coronary resistance. The high PaO2-induced coronary vasoconstriction was not affected by administration of indomethacin, nordihydroguaiaretic acid, NG-nitro-L-arginine, or superoxide dismutase and catalase but was abolished after endothelium damage or by cromakalim. These results demonstrate that 1) the endothelium contributes to the high PaO2-induced coronary vasoconstriction; 2) this effect is independent of cyclooxygenase or lipoxygenase products, nitric oxide, or free radicals; and 3) the closure of ATP-sensitive K+ channels mediates this vasoconstriction.
Subject(s)
Coronary Vessels/physiology , Oxygen/blood , Vasoconstriction/physiology , Adenosine Triphosphate/pharmacology , Arteries , Coronary Vessels/drug effects , Coronary Vessels/physiopathology , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Free Radicals/metabolism , Humans , Lipoxygenase/metabolism , Nitric Oxide/metabolism , Octoxynol/pharmacology , Partial Pressure , Potassium Channels/drug effects , Potassium Channels/physiology , Prostaglandin-Endoperoxide Synthases/metabolismABSTRACT
BACKGROUND: Experimental studies suggest that the new short-acting intravenous anesthetic agent eltanolone does not markedly alter hemodynamics or cardiac function. However, because its intrinsic effects on myocardial performance and coronary blood flow are not yet known, they were examined in isolated blood-perfused rabbit hearts. METHODS: Coronary blood flow, myocardial contractility, relaxation, and oxygen consumption were measured during perfusion of hearts with 0.1 to 10 micrograms/ml eltanolone (n = 7) or its vehicle (n = 7). To determine whether the cardiac effects of eltanolone are mediated by indirect sympathetic activation, the same dose-response curve was studied in another group of five hearts depleted of catecholamine with reserpine treatment. RESULTS: Coronary blood flow significantly increased with 10 micrograms/ml eltanolone and significantly decreased with 10 micrograms/ ml eltanolone vehicle. At eltanolone concentrations less than 10 micrograms/ml, myocardial contractility and relaxation remained unchanged but decreased at 10 micrograms/ml. Myocardial contractility and relaxation were not affected by perfusion of eltanolone vehicle alone. In eltanolone-perfused hearts, unchanged myocardial oxygen consumption was associated with significant increases in coronary venous oxygen content and tension, but in vehicle-perfused hearts, it was associated with reduced coronary venous oxygen content and tension. In catecholamine-depleted hearts, the variations in myocardial performance and coronary blood flow induced by eltanolone were similar to those observed in intact hearts. CONCLUSIONS: Eltanolone (0.1 to 3 micrograms/ml) did not alter myocardial performance or coronary blood flow in isolated blood-perfused rabbit hearts. These effects were not due to an eltanolone-induced indirect sympathetic activation. Cardiac depression and coronary vasodilatation were only observed at concentrations of eltanolone far greater than those in clinical range.
