COMBINED INOTROPIC EFFECTS OF AMRINONE AND EPINEPHRINE AFTER CARDIOPULMONARY BYPASS IN HUMANS

Amrinone, a phosphodiesterase inhibitor, and epinephrine, an alpha- an d beta-adrenergic receptor agonist, are inotropic drugs used during ca rdiac surgery to reverse myocardial depression after cardiopulmonary b ypass. However, these drugs have not been compared separately, or in c ombination, in this patient population. We hypothesized that the combi nation might have complementary actions in improving myocardial functi on. We, therefore, compared amrinone, epinephrine, and the combination of amrinone and epinephrine in a randomized, blinded, placebo-control led study in patients undergoing coronary artery bypass grafting. Fort y patients with ejection fractions > 0.45 were studied. Right ventricu lar ejection fraction pulmonary artery catheters and radial arterial c atheters were inserted before fentanyl-midazolam anesthesia. After sep aration from bypass, patients received either a placebo (n = 20) or am rinone bolus (1.5 mg/kg, n = 20) at time 0 and a placebo (n = 20) or e pinephrine (30 ng.kg-1 . min-1, n = 20) infusion at time 5 min. This r esulted in four study groups, n = 10 in each group. Data were collecte d every 2.5 min for 10 min: Epinephrine, amrinone, and the combination of both drugs significantly increased cardiac output, stroke volume, 02 delivery, and left ventricular stroke work. The increase in stroke volume (P < 0.05) was 12 +/- 6,16 +/- 4, and 30 +/- 4 mL/beat with epi nephrine, amrinone, and the combination of amrinone and epinephrine, r espectively. The amrinone-epinephrine combination increased stroke vol ume as much as the sum of amrinone and epinephrine given separately. S ystemic vascular resistance and pulmonary vascular resistance decrease d with amrinone and amrinone-epinephrine, but not with epinephrine. Ep inephrine increased mean arterial and mean pulmonary arterial pressure s. Right ventricular ejection fraction did not significantly increase (P = 0.09) with epinephrine, but increased significantly with amrinone (0.45 to 0.53, P = 0.01), and with the combination (0.43 to 0.55, P = 0.006). These data indicate that amrinone and epinephrine effectively increase myocardial performance during cardiac surgery. Right ventric ular function especially was improved with amrinone and the combinatio n of amrinone and epinephrine. The combined effects of amrinone and ep inephrine may be useful in patients recovering from the ischemia and r eperfusion injury resulting from coronary artery bypass grafting.