Inhaled nitric oxide and inhaled prostaglandin E1: effect on left ventricular contractility when used for treatment of experimental pulmonary hypertension

Abstract

Objective: Pulmonary hypertension (PHT) is a life-threatening complication after isolated heart and lung transplantation. Recent work has shown that inhaled nitric oxide (NO) in combination with inhaled prostaglandin E1 (PGE1) reduce pulmonary hypertension but their influence on cardiac contractility is less well defined.

Methods: This study investigated left ventricular contractility as measured by the 'Preload Recruitable Stroke Work-Relation' (PRSW) in 24 anesthetized open chest pigs, 12 receiving in random order NO (50 ppm), PGE1 (20 microg/ml) and their combination compared to 12 controls. PHT was induced by embolization with glass beads (500 microm). Prior to induction of PHT, sonomicrometric crystals were placed on the heart to measure instantaneous cardiac dimensions. Instantaneous intraventricular pressure (micro-tip catheter) and intraventricular dimensions were recorded digitally, while intraventricular volumes were calculated from the intraventricular dimensions applying the cylindric ellipsoidal volume model for the left ventricle. PRSW was calculated from the instantaneous pressure and volume data during rapid vena caval occlusion by analysis of generated pressure-volume loops. All data were analyzed by MANOVA and corrected for heart rate (level of significance #: P < 0.05); PRSW-slope measures contractility, (PRSW-X-intercept did not change significantly).

Results: PRSW-change +/- SEM (in percent of initial PRSW after induction of PHT) was -14.6% +/- 4.4% versus 1.6% +/- 4.4% for NO versus Control (P = 0.004), -8.8% +/- 4.6% versus 1% +/- 3.3% (P = 0.18) for PGE1 versus Control and -5.7% +/- 4.4% versus 2.5% +/- 4.2% for NO + PGE1 versus Control (P = 0.33), respectively. In summary, application of NO 50 ppm significantly reduced left ventricular contractility while PGE1 20 microg/ml and the combination of NO and PGE1 did not.

Conclusion: If NO is not available, the sole application of nebulized PGE1 (20 microg/ml) appears to be safe with respect to left ventricular contractility in the setting of PHT. The combination of NO and PGE1 for the treatment of pulmonary hypertension should be considered for clinical application in situations where a combination of pulmonary hypertension and decreased left ventricular function is present.