PRESERVATION OF MYOCYTE CONTRACTILE FUNCTION AFTER HYPOTHERMIC, HYPERKALEMIC CARDIOPLEGIC ARREST WITH 2,3-BUTANEDIONE MONOXIME

One proposed contributory mechanism for depressed ventricular performa nce after hypothermic, hyperkalemic cardioplegic arrest is a reduction in myocyte contractile function caused by alterations in intracellula r calcium homeostasis. Because 2,3-butanedione monoxime decreases intr acellular calcium transients, this study tested the hypothesis that 2, 3-butanedione monoxime supplementation of the hyperkalemic cardioplegi c solution could preserve isolated myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Myocytes were isolated from the left ventricles of six pigs. Magnitude and velocity of myocyt e shortening were measured after 2 hours of incubation under normother mic conditions (37 degrees C, standard medium), hypothermic, hyperkale mic cardioplegic arrest (4 degrees C in Ringer's solution with 20 mEq potassium chloride), and hypothermic, hyperkalemic cardioplegic arrest with 2,3-butanedione monoxime supplementation (4 degrees C in Ringer' s solution with 20 mEq potassium chloride and 20 mmol/L 2,3-butanedion e monoxime). Because beta-adrenergic agonists are commonly employed af ter cardioplegic arrest, myocyte contractile function was examined in the presence of the beta-agonist isoproterenol (25 nmol/L). Hypothermi c, hyperkalemic cardioplegic arrest and rewarming reduced the velocity (32%) and percentage of myocyte shortening (27%, p < 0.05). Supplemen tation with 2,3-butanedione monoxime normalized myocyte contractile fu nction after hypothermic, hyperkalemic cardioplegic arrest. Although b eta-adrenergic stimulation significantly increased myocyte contractile function under normothermic conditions and after hypothermic, hyperka lemic cardioplegic arrest, contractile function of myocytes exposed to beta-agonist after hypothermic, hyperkalemic cardioplegic arrest rema ined significantly reduced relative to the normothermic control group. Supplementation with 2,3-butanedione monoxime restored beta-adrenergi c responsiveness of myocytes after hypothermic, hyperkalemic cardiople gic arrest. Thus, supplementation of a hyperkalemic cardioplegic solut ion with 2,3-butanedione monoxime had direct and beneficial effects on myocyte contractile function and beta-adrenergic responsiveness after cardioplegic arrest. A potential mechanism for the effects of 2,3-but anedione monoxime includes modulation of intracellular calcium transie nts or alterations in sensitivity to calcium. Supplementation,vith 2,3 -butanedione monoxime may have clinical utility in improving myocardia l contractile function after hypothermic, hyperkalemic cardioplegic ar rest.