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 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.

The dose-dependent effects of halothane on right ventricular contraction pattern and regional inotropy in swine.

The right ventricle (RV) is comprised of two embryologically distinct units, the inflow and outflow tracts, which normally contract sequentially and differ in the magnitude of increased inotropy during sympathetic nervous stimulation. The present study examined the dose-response effects of halothane on the RV contraction pattern and regional contractility in seven open-chest pigs instrumented for measurement of inflow and outflow tract pressures and segment lengths. The RV contraction pattern was evaluated by comparing the phase of inflow and outflow tract shortening, and regional contractility was determined by calculation of preload recruitable stroke work (PRSW) slope. Using this methodology, an inflow-outflow tract contraction phase difference of -27 degrees (inflow tract shortened earlier) was evident at baseline, but was abolished by 1.0 and 1.5 minimum alveolar anesthetic concentration (MAC) halothane; PRSW slope of both the inflow and outflow tracts, however, demonstrated similar dose-related change. To determine whether alterations in cardiac sympathovagal balance played a role in the RV response to halothane, an additional four animals were studied after pretreatment with hexamethonium, propranolol, and atropine. In these animals, there was no difference in the regional contraction phase either at baseline or during halothane administration, and dose-related depression of PRSW by halothane was again similar in both regions. However, when halothane effects on regional PRSW in animals with autonomic blockade were compared to those of neurally intact animals, a 20% greater depression of outflow tract PRSW by 0.5 MAC halothane was evident. This study demonstrates that halothane abolishes the normal sequential pattern of RV contraction without exerting markedly variant negative inotropic effects within different regions of the RV, and provides evidence to suggest that alterations in cardiac sympathovagal balance may contribute to the effect of halothane on RV contraction dynamics.