NITRIC-OXIDE MODULATION OF PULMONARY BLOOD-FLOW DISTRIBUTION IN LOBARHYPOXIA

Background: Nitric oxide, endogenously produced or inhaled, has been s hown to play an important role in the regulation of pulmonary blood fl ow. The inhalation of nitric oxide reduces pulmonary arterial pressure in humans, and the blockade of endogenous nitric oxide production inc reases the pulmonary vascular response to hypoxia. This study was perf ormed 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 duri ng regional hypoxia. Methods: Hypoxia (5% O-2) was induced in the left lower lobe of the pig, and the blood now to this lobe was measured wi th transit-time ultrasound. Nitric oxide was administered in the gas v entilating the hypoxic lobe and the hyperoxic lung regions with and wi thout blockade of endogenous nitric oxide production by means of N-ome ga-nitro-L-arginine methyl ester (L-NAME). Results: Hypoxia in the lef t lower lobe reduced blood now to that lobe to 27 +/- 3.9% (mean +/- S EM) of baseline values (P < 0.01), L-NAME caused a further reduction i n lobar blood how in all six animals to 12 +/- 3.5% and increased arte rial oxygen tension (Pa-O2 (P < 0.01). Without L-NAME, the inhalation of nitric oxide (40 ppm) to the hypoxic lobe increased lobar blood flo w 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 +/- 93% of baseline (difference not significant). When nitric oxid e was administered to the hyperoxic lung regions, after L-NAME infusio n, the blood flow to the hypoxic lobe decreased to 2.5 +/- 1.6% of bas eline and Pa-O2 was further increased (P < 0.01). Conclusions: By vari ous combinations of nitric oxide inhalation and intravenous administra tion of an nitric oxide synthase inhibitor, lobar blood flow and arter ial oxygenation could be markedly altered during lobar hypoxia. In par ticular, the combination of intravenous L-NAME and nitric oxide inhala tion to the hyperoxic regions almost abolished perfusion of the hypoxi c lobe and resulted in a Pa-O2 that equalled the prehypoxic values. Th is possibility of adjusting regional blood flow and thereby of improvi ng Pa-O2 may be of value in the treatment of patients undergoing one-l ung ventilation and of patients with acute respiratory failure.