NITRIC-OXIDE SYNTHESIS INHIBITION AND RIGHT-VENTRICULAR SYSTOLIC FUNCTION IN SWINE

Objectives: The present study was designed to evaluate the effects of the nitric oxide synthesis inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) on right ventricular (RV) contractility, both pulsatile and nonpulsatile contributions to afterload, and relate any changes to alt erations in performance of the RV as a pump. Design: Prospective drug response. Setting: University animal laboratory. Participants: Swine. Interventions: Six pigs anesthetized with thiopental and fentanyl were instrumented for measurement of RV pressure and pulmonary arterial (P A) pressure, internal diameter, and blood flow. Total RV afterload was calculated as effective PA elastance, with the steady-state component expressed as total arterial resistance, and the pulsatile component a ssessed by calculation of characteristic impedance and global complian ce. The ratio of peak PA flow to RV en;l-diastolic pressure (RVEDP) wa s recorded as an index of RV pump function, and the peak ejection rate -of-change of RV power (dPower/dt) was calculated as an index of contr actility. In each animal, measurements were obtained before (baseline) and 15 minutes after intravenous injection of 33 mg/kg of L-NAME. Mea surements and Main Results: Mean PA pressure increased from 14 +/- 3 m mHg at baseline to 23 +/- 6 mmHg after L-NAME, whereas cardiac output, stroke volume, and peak PA flow/RVEDP demonstrated declines and dPowe r/dt was unchanged. Simultaneously, effective PA elastance increased m ore than twofold. This increase in total RV afterload was primarily th e result of a marked elevation in total arterial resistance (+156%), w hereas vascular compliance was reduced by only 30% and characteristic impedance unchanged. Conclusions: These data indicate that L-NAME prod uces constriction of resistance vessels within the lung, leading to in creased steady-state RV afterload, but has little direct effect on lar ge pulmonary vessels and pulsatile RV load. RV pump performance declin es after L-NAME, but contractility is preserved, indicating that the c hange in systolic performance results primarily from the increase in s teady-state afterload. Copyright (C) 1996 by W.B. Saunders Company