monensin and Coronary-Disease

Maintenance of low coronary flow (1 ml/min) during 40 or 70 min of anoxia maintained function and prevented Ca2+ overload during reoxygenation in isolated rat hearts. In comparison, recovery from 40 min of global ischemia resulted in only 20% of preischemic function and an increase in end-diastolic pressure (LVEDP) to 39 mmHg. Reperfusion Ca2+ uptake rose from 0.6 to 10.2 mumol/g dry tissue. Intracellular Na+ (Nai+) increased from 13 to 61 mumol/g dry tissue after 40 min of global ischemia, but was unchanged in hearts with low flow anoxia. When glucose and pyruvate were omitted from buffer used for anoxic perfusion, recovery was only 15% of preanoxic values, LVEDP rose to 32 mmHg, and reperfusion Ca2+ uptake was 7.2 mumol/g dry. In addition, Nai+ increased (47.4 mumol/g dry tissue) and ATP was depleted (1.0 mumol/g dry tissue) in the absence of substrate. In anoxic hearts supplied substrate, Nai+ stayed low (12 mumol/g dry tissue) and ATP was preserved (11.6 mumol/g dry tissue). Addition of ouabain (100 or 200 microM) and provision of zero-K+ buffer increased Nai+ and resulted in impaired functional recovery, increased LVEDP, and greater reperfusion Ca2+ uptake. These interventions also decreased energy availability in anoxic hearts. To distinguish between effects of Na+ accumulation and ATP depletion, monensin, a Na+ ionophore, was added during low flow anoxia. Monensin increased Nai+, decreased functional recovery and increased reperfusion Ca2+ uptake in a dose-dependent manner (1-10 microM) without changing ATP content. These results suggested that reduction of Nai+ accumulation by maintenance of Na+, K+ pump activity was the major mechanism of the beneficial effects of low coronary flow on reperfusion injury.

Topics: Adenosine Triphosphate; Animals; Biological Transport, Active; Calcium; Coronary Circulation; Coronary Disease; Energy Metabolism; Hypoxia; In Vitro Techniques; Male; Monensin; Myocardial Reperfusion Injury; Myocardium; Perfusion; Rats; Rats, Inbred Strains; Sodium; Sodium-Potassium-Exchanging ATPase

Topics: Animal Feed; Animals; Cattle; Chickens; Coronary Circulation; Coronary Disease; Dogs; Dose-Response Relationship, Drug; Erythrocytes; Food Additives; Furans; Humans; Ionophores; Kinetics; Molecular Conformation; Monensin; Muscle, Smooth, Vascular; Rabbits; Vascular Resistance

Topics: Animals; Coronary Circulation; Coronary Disease; Dogs; Dose-Response Relationship, Drug; Female; Furans; Hemodynamics; Male; Monensin; Myocardium; Oxygen Consumption; Vasodilator Agents