Nitric oxide dose response during moderate and severe hypoxia in swine

Elucidation of factors that influence the dose response to inhaled nitric oxide is crucial to optimizing its therapeutic benefit. We investigated whether severity of hypoxia is one such factor.

Seven Yorkshire swine underwent 14 triphasic experiments: (1) control period of mechanical ventilation (fractional concentration of oxygen = 0.3); (2) induction of hypoxic pulmonary hypertension (fractional concentration of oxygen = 0.1 to 0.15); and (3) inhaled nitric oxide at 5, 10, 20, 40, and 80 parts per million (ppm). Hemodynamics and arterial blood gases were measured by pulmonary and systemic arterial catheters.

Experiments were divided into two groups of seven based on hypoxia severity: severe (arterial oxygen tension, 25 to 40 mm Hg) and moderate (arterial oxygen tension, 41 to 60 mm Hg). The percent changes in mean pulmonary artery pressure after each dose were compared within each group by repeated measure analysis of variance and each dose was compared between the two groups by Student's t test. A statistically significant dose response existed in both groups (p < 0.02). Low doses resulted in significantly less vasodilation in the severe versus the moderate hypoxia group (5 ppm, 59% +/- 6% versus 94% +/- 7%, p = 0.003; 10 ppm, 69% +/- 8% versus 99% +/- 8%, p = 0.017).

Lower doses are significantly less effective in achieving maximal pulmonary vasodilation during severe hypoxia. Therefore, the degree of hypoxia is a determinant of the inhaled nitric oxide dose response.