AMRINONE COMBINED WITH DOBUTAMINE IMPROVES HEMODYNAMICS AND OXYGEN DELIVERY WITHOUT DOWN-REGULATION OF CARDIAC BETA-ADRENERGIC-RECEPTOR DENSITY IN PORCINE ENDOTOXEMIA

Effects of amrinone (AMR), a phosphodiesterase inhibitor, alone and in combination with dobutamine (DOB), on hemodynamics and O-2 delivery were studied during porcine endotoxemia. Pentobarbital-anesthetized pigs were randomly administered either Escherichia coli lipopolysaccharide (endotoxin) or equivolumetric .9% NaCl (control) as a continuous infusion for 4 h. From 2 to 4 h (T = 120-240 min) of endotoxin infusion, pigs were randomly administered one of the following treatments; AMR infusion (40 mu g/kg/min) (AMR(low)); DOB (10 mu g/kg/min) (DOB); AMR infusion (40 mu g/kg/min) + DOB (AMR(low) + DOB); AMR bolus (.75 mg/kg) followed by AMR infusion (40 mu g/kg/min) (AMR(high)); or AMR bolus (.75 mg/kg) followed by infusion (40 mu g/kg/min) + DOB (AMR(high) + DOB). Myocardial samples were obtained at the end of the experiment and flash-frozen for beta-adrenergic receptor analysis. Endotoxin significantly (p <.05) decreased cardiac index, right ventricular ejection fraction, stroke volume index, maximum rate of rise of left ventricular pressure (dP/dt(max)) mean arterial pressure, and O-2 delivery, and increased pulmonary vascular resistance and mean pulmonary arterial pressure (p <.05). AMR(low) + DOB significantly (p <.05) increased cardiac index, dP/dt(max), right ventricular ejection fraction, stroke volume index, O-2 delivery and consumption, and decreased mean pulmonary arterial pressure, pulmonary vascular resistance, mean arterial pressure, and systemic vascular resistance. beta-Adrenergic receptor density (B-max) and binding equilibrium dissociation constant (K-D) for [H-3]dihydroalprenolol were not affected by endotoxin or any treatment (p <.05). Endotoxin-induced hemodynamic deterioration and decreased O-2 delivery was attenuated by AMR(low) + DOB. Potential applications of this combination may exist in treatment of septic patients with inadequate myocardial performance and reduction in O-2 delivery complicated by pulmonary hypertension.