Inhaled nitric oxide after lung ischemia reperfusion; effect on hemodynamics and oxygen free radical scavenger system

Abstract

Objective: Pulmonary hypertension and transient graft dysfunction may complicate the postoperative course of patients undergoing lung transplantation. Recent studies have suggested that ischemia followed by reperfusion impairs release of endothelium-derived nitric oxide (NO). We investigated the acute effect of inhaled NO on hemodynamics and the oxygen free radical scavenger system after reperfusion following lung ischemia.

Methods: Fourteen anesthetized mongrel dogs were ventilated mechanically. After median sternotomy the left lung was rendered ischemic by totally clamping the left pulmonary hilum. After 90 min, the left lung was reperfused for 150 min by unclamping of the left hilum and clamping the right pulmonary hilum so that all pulmonary blood flow was directed to the left lung. Seven dogs inhaled 30 parts per million (ppm) NO during reperfusion (NO group); the other seven dogs were ventilated without NO inhalation (control group). Hemodynamics, gas exchange, superoxide dismutase activity and lipid peroxide of pulmonary venous blood, and wet/dry ratio of reperfused lung were measured.

Results: Neither of the two groups showed any change in systemic blood pressure prior to or following reperfusion. Immediately after reperfusion, mean pulmonary arterial pressure was significantly less (23.2 +/- 4.2 mmHg) in the NO group than in the control group (32.7 +/- 5.8 mmHg), as had been throughout reperfusion. Pulmonary vascular resistance and right ventricular end diastolic pressure were lower after reperfusion in the NO group. Superoxide dismutase activity after reperfusion in the control group significantly decreased to 41% of preischemic value. In the NO group, however, no decrease was seen and a significantly higher value was observed. The wet/dry ratio of reperfused lung was 5.47 +/- 0.52 in the control group and 4.72 +/- 0.36 in the NO group, with decreased pulmonary moisture noted in the NO group. There was no difference in lipid peroxide between the two groups.

Conclusion: NO inhalation suppressed pulmonary hypertension after reperfusion following lung ischemia without affecting systemic arterial pressure. As superoxide dismutase activity was not depressed in the NO group, NO inhalation might enhance suppression of oxygen free radicals. These findings suggest that NO inhalation may be therapeutically useful after lung transplantation.