Nitric oxide synthesis inhibition and right ventricular systolic function in swine.
Academic Article
Overview
abstract
OBJECTIVES: The present study was designed to evaluate the effects of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on right ventricular (RV) contractility, both pulsatile and nonpulsatile contributions to afterload, and relate any changes to alterations 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 (PA) 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 assessed by calculation of characteristic impedance and global compliance. The ratio of peak PA flow to RV end-diastolic pressure (RVEDP) was 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 contractility. In each animal, measurements were obtained before (baseline) and 15 minutes after intravenous injection of 33 mg/kg of L-NAME. MEASUREMENTS AND MAIN RESULTS: Mean PA pressure increased from 14 +/- 3 mmHg at baseline to 23 +/- 6 mmHg after L-NAME, whereas cardiac output, stroke volume, and peak PA flow/RVEDP demonstrated declines and dPower/dt was unchanged. Simultaneously, effective PA elastance increased more than twofold. This increase in total RV afterload was primarily the result of a marked elevation in total arterial resistance (+156%), whereas vascular compliance was reduced by only 30% and characteristic impedance unchanged. CONCLUSIONS: These data indicate that L-NAME produces constriction of resistance vessels within the lung, leading to increased steady-state RV afterload, but had little direct effect on large pulmonary vessels and pulsatile RV load. RV pump performance declines after L-NAME, but contractility is preserved, indicating that the change in systolic performance results primarily from the increase in steady-state afterload.
