HEMODYNAMIC-EFFECTS OF N-ACETYLARINONE IN A PORCINE MODEL OF GROUP-B STREPTOCOCCAL SEPSIS

High plasma concentrations of N-acetylamrinone, a primary metabolite o f amrinone, are measured in some children during prolonged amrinone in fusion. the purpose of this investigation was to determine if N-acetyl amrinone has direct hemodynamic effects independent of amrinone, Twent y neonatal piglets received an infusion of 6 x 10(9) colony-forming un its/kg of group B Streptococcus to induce sepsis, Subsequently, they w ere divided into 1 of 3 groups and received a 1-hr infusion of either normal saline (N = 4); 8 mg/kg amrinone, followed by 20 mu g/kg/min (N = 9); or 8 mg/kg N-acetylamrinone, followed by 20 mu g/kg/min (N = 7) , Hemodynamic measurements and arterial/venous blood-gas determination s were obtained every 30 min during the study. Systemic vascular resis tance and pulmonary vascular resistance were calculated. One millilite r of blood was obtained every 30 min during drug administration to det ermine plasma amrinone and N-acetylamrinone concentrations. The mean a mrinone plasma concentrations measured at 30 and 60 min during the inf usion time in the group receiving amrinone were 8.8 +/- 1.1 and 6.9 +/ - 0.7 mu g/ml, respectively, These animals experienced a significant d ecrease in mean pulmonary artery pressure and pulmonary vascular resis tance, compared with saline controls after a 30-min infusion of amrino ne, The mean N-acetylamrinone plasma concentrations measured at 30 and 60 min during the N-acetylamrinone infusion were 7.3 +/- 0.8 and 5.7 +/- 0.6 mu g/ml, respectively. There was no difference between any hem odynamic parameter measured in these animals, compared with saline con trols at any time during the infusion, We conclude that amrinone, hut not N-acetylamrinone, causes pulmonary vasodilation in a porcine model of sepsis and that the parent drug is the sole active component in am rinone.