THE DIRECT AND INTERACTIVE EFFECTS OF PHOSPHODIESTERASE INHIBITION AND P-ADRENERGIC STIMULATION ON MYOCYTE CONTRACTILE FUNCTION AFTER HYPOTHERMIC CARDIOPLEGIC ARREST

The direct and interactive effects of phosphodiesterase inhibition (PD EI) and beta-adrenergic receptor (beta AR) stimulation on isolated myo cyte contractile function were examined after hypothermic, hyperkalemi c, cardioplegic arrest (HHCA) and under normothermic conditions. Left ventricular (LV) myocytes were isolated from porcine hearts and myocyt e contractile function was measured under normothermic conditions (37 degrees C in standard media) and after HHCA (2 h at 4 degrees C in Rin ger's solution with 24 mEq KCl) with subsequent rewarming. Myocytes we re then randomly assigned to treatment with the PAR agonist isoprotere nol (25 nM), the phosphodiesterase inhibitor amrinone (50 mu M), or a combination of these compounds and contractile function measurements r epeated. Baseline myocyte contractile function was reduced by 32% afte r HHCA. Isoproterenol alone increased myocyte contractile function mor e than 100% under both normothermic conditions and after HHCA, whereas amrinone alone significantly (60%) improved myocyte contractile funct ion only after HHCA. Amrinone preincubation followed by isoproterenol improved contractile function after HHCA to a greater extent than all other treatment protocols. In contrast, combination treatment under no rmothermic conditions did not augment myocyte contractile function rel ative to isoproterenol alone. These findings suggest that amrinone has differential effects on contractile processes. Moreover, the marked i mprovement of contractile function after HHCA with PDEI pretreatment f ollowed by beta AR stimulation may have implications in treatment stra tegies for improving myocardial function after cardiopulmonary bypass and provide insight into contractile dysfunction after HHCA.