EFFECT OF AMRINONE DURING GROUP-B STREPTOCOCCUS-INDUCED PULMONARY-HYPERTENSION IN PIGLETS

Intravenous infusion of group B Streptococcus (GBS) into neonatal animals produces pulmonary hypertension, ventilation/perfusion (V(A)/Q mismatch, and an increase in serum levels of thromboxane B2 (TxB2) and tumor necrosis factor (TNF)alpha. The vasodilator amrinone (amr) is a cGMP-inhibited phosphodiesterase inhibitor and is reported to inhibit thromboxane A2 and TNF production. We hypothesized that infusion of amr would cause pulmonary vasodilation and reduce serum TxB2 and TNF levels in piglets with late phase GBS-induced pulmonary hypertension. The effect of amr on gas exchange was also determined. A continuous infusion of GBS was administered for 5 hr to 4 groups of anesthetized, mechanically ventilated neonatal piglets. An amr bolus of 8 mg/kg was given at 4 hr followed by a 1 hr continuous infusion of either 10 or 20 mug/kg/min of amr (amr 10 and amr 20, respectively). Control piglets received a bolus and 1 hr infusion of amr carrier. The infusion of amr, but not of carrier reversed late phase GBS-induced pulmonary hypertension. Piglets infused with amr 20 showed transient selective pulmonary vasodilation, based on a reduced ratio of pulmonary to systemic vascular resistance (PVR/SVR ratio) value at 30 min but not at 1 hr, compared to pre-amr treatment values. The PVR/SVR ratio values for amr 10 and control group did not change after treatment with either amr or carrier. Treatment with amr 10 or 20 did not decrease serum TxB, or TNF levels or increase V(A)/Q mismatch. A subsequent group of piglets received an 8 mg/kg bolus and 40 mug/kg/min infusion of amr (amr 40) to determine if the increased infusion rate would sustain a selective pulmonary vasodilatory effect beyond 30 min. The PVR/SVR ratio values for amr 40 did not change after treatment for 30 min or 1 hr, compared to pretreatment values. We conclude that amr is effective in reversing GBS-induced pulmonary hypertension. However, the reduction in SVR caused by amr may preclude its use in septic newborns. (C) 1993 Wiley-Liss, Inc.