Objective: To test the hypothesis that in a swine model of acute respiratory distress syndrome (ARDS) with permissive hypercapnia, inhaled nitric oxide would improve transpulmonary vascular mechanics and right ventricular workload while not changing intrinsic right ventricular contractility.
Design: Prospective, randomized, controlled laboratory trial.
Setting: University research laboratory.
Subjects: Eleven swine (30 to 46 kg).
Interventions: The swine were anesthetized, intubated, and paralyzed. After median sternotomy, pressure transducers were placed in the right ventricle, pulmonary artery, and left atrium. An ultrasonic flow probe was placed around the pulmonary artery. Ultrasonic dimension transducers were sutured onto the heart at the base, apex, left ventricle (anterior, posterior, free wall), and right ventricle (free wall). An additional transducer was placed in the interventricular septum. A surfactant depletion model of ARDS was created by saline lung lavage. Nitric oxide was administered at 2, 4, and 6 parts per million (ppm), in a random order, under the condition of permissive hypercapnia (Paco2 55 to 75 torr [7.3 to 10.0 kPa]).
Measurements and main results: We evaluated the pulmonary vascular and right ventricular effects of permissive hypercapnia, with and without inhaled nitric oxide, by measuring variables of transpulmonary vascular mechanics and right ventricular function. These variables included mean pulmonary arterial pressure, right ventricular total power, right ventricular stroke work, transpulmonary vascular efficiency, and right ventricular intrinsic contractility. Data were obtained after lung injury under the following conditions: a) normocapnia (Paco2 35 to 45 torr [4.7 to 6.0 kPa]) and nitric oxide at 0 ppm; b) hypercapnia and nitric oxide at 0 ppm; c) hypercapnia and nitric oxide at 2, 4, and 6 ppm; and d) repeat measurements with hypercapnia and nitric oxide at 0 ppm. In ARDS with permissive hypercapnia, inhaled nitric oxide therapy (2 to 6 ppm) improved transpulmonary vascular mechanics and right ventricular workload by lowering pulmonary arterial pressure (29.6 +/- 1.3 vs. 24.6 +/- 1.0 mm Hg, p = .0001), increasing transpulmonary vascular efficiency (13.9 +/- 0.5 vs. 16.1 +/- 0.7 L/W-min, p = .0001), decreasing right ventricular total power (142 +/- 9 vs. 115 +/- 9 mW, p = .001), and decreasing right ventricular stroke work (653 +/- 37 vs. 525 +/- 32 ergs x 10(3), p = .001). Inhaled nitric oxide did not change right ventricular contractility, as measured by preload-recruitable stroke work.
Conclusions: Inhaled nitric oxide ameliorated any negative effects of hypoxic and hypercapnic pulmonary vasoconstriction. The beneficial effects of inhaled nitric oxide are related to alterations in right ventricular afterload and not intrinsic right ventricular contractility. The improved cardiopulmonary effects of inhaled nitric oxide with permissive hypercapnia potentially expand the use of nitric oxide in ARDS and other conditions in which this strategy is employed.