The effect of a combination of inhaled nitric oxide and an endothelinA-receptor antagonist on hemodynamic dysfunction in experimental acute pulmonary thromboembolism.

Although either inhaled nitric oxide (NO) or endothelinA receptor antagonist has been tried in the treatment of various forms of pulmonary hypertension, the effects of combination therapy have not been reported. We evaluated the effects of inhaled NO alone or a combination of inhaled NO and ZD2574 (an endothelinA receptor antagonist) in an experimental canine acute pulmonary thromboembolism model. Forty parts per million of inhaled NO alone, or a combination of inhaled NO and 10 mg/kg of ZD2574 was administered 1 hour after embolization with an autologous blood clot. We compared the hemodynamic and gas exchange parameters between the two treatment groups. Two treatment regimens decreased mean pulmonary arterial pressure and pulmonary vascular resistance and attenuated decrease in cardiac output. Moreover, systemic arterial hypotension or worsening of hypoxemia did not occur in either of the treatment groups. In the combined group, more favorable hemodynamic outcomes were maintained than in the inhaled NO alone group. And hemodynamic deterioration shown after NO withdrawal was attenuated in the combined group. These findings suggest that when inhaled NO is concomitantly administered with an ETA receptor antagonist, more favorable hemodynamic outcomes can be expected during and after NO inhalation in acute pulmonary thromboembolism.