Background
Nitric oxide, endogenously produced or inhaled, has been shown to play an important role in the regulation of pulmonary blood flow. The inhalation of nitric oxide reduces pulmonary arterial pressure in humans, and the blockade of endogenous nitric oxide production increases the pulmonary vascular response to hypoxia. This study was performed to investigate the hypothesis that intravenous administration of an nitric oxide synthase inhibitor and regional inhalation of nitric oxide can markedly alter the distribution of pulmonary blood flow during regional hypoxia.
Methods
Hypoxia (5% O2) was induced in the left lower lobe of the pig, and the blood flow to this lobe was measured with transit-time ultrasound. Nitric oxide was administered in the gas ventilating the hypoxic lobe and the hyperoxic lung regions with and without blockade of endogenous nitric oxide production by means of N omega-nitro-L-arginine methyl ester (L-NAME).
Results
Hypoxia in the left lower lobe reduced blood flow to that lobe to 27 +/- 3.9% (mean +/- SEM) of baseline values (P < 0.01). L-NAME caused a further reduction in lobar blood flow in all six animals to 12 +/- 3.5% and increased arterial oxygen tension (PaO2) (P < 0.01). Without L-NAME, the inhalation of nitric oxide (40 ppm) to the hypoxic lobe increased lobar blood flow to 66 +/- 5.6% of baseline (P < 0.01) and, with L-NAME, nitric oxide delivered to the hypoxic lobe resulted in a lobar blood flow that was 88 +/- 9.3% of baseline (difference not significant). When nitric oxide was administered to the hyperoxic lung regions, after L-NAME infusion, the blood flow to the hypoxic lobe decreased to 2.5 +/- 1.6% of baseline and PaO2 was further increased (P < 0.01).
Conclusions
By various combinations of nitric oxide inhalation and intravenous administration of an nitric oxide synthase inhibitor, lobar blood flow and arterial oxygenation could be markedly altered during lobar hypoxia. In particular, the combination of intravenous L-NAME and nitric oxide inhalation to the hyperoxic regions almost abolished perfusion of the hypoxic lobe and resulted in a PaO2 that equalled the prehypoxic values. This possibility of adjusting regional blood flow and thereby of improving PaO2 may be of value in the treatment of patients undergoing one-lung ventilation and of patients with acute respiratory failure.
930-103 Endogenous Nitric Oxide Production Contributes to Increases in Coronary Blood Flow During Exercise
