CHRONIC INFUSION OF NITRIC-OXIDE IN EXPERIMENTAL PULMONARY-HYPERTENSION - PULMONARY PRESSURE-FLOW ANALYSIS

Inhaled-nitric oxide (NO) is a selective pulmonary vasodilator in shor tterm clinical studies, Use of NO inhalation in chronic pulmonary hype rtension is complicated by potential problems with ambulatory NO deliv ery, We hypothesized that long-term infusion of NO solution into the c entral venous circulation, which did not suffer from this drawback, mi ght reduce chronic pulmonary hypertension. Saturated NO solution was i nfused in chronically hypoxic rats by implantable minipumps at a rate which was effective in reducing acute hypoxic vasoconstriction in isol ated, Krebs' albumin perfused lungs (2.5 mu L . h(-1)). Pulmonary haem odynamics and the pressure-flow relationship were studied after 4 week s of infusion. NO was still present in the minipumps at the end of the infusion period, Despite causing methaemoglobinaemia, NO infusion did not significantly attenuate pulmonary arterial pressure, pulmonary va scular resistance, right ventricular hypertrophy, or the parameters of the pulmonary vascular pressure-now relationship, Pressure-now curves , analysed with the nonlinear, distensible vessel model, indicated inc reased near-zero pressure resistance (Ro) in chronic hypoxia. The tend ency of chronic NO infusion to reduce Ro did not reach statistical sig nificance. Long-term infusion of nitric oxide solution is technically feasible but does not effectively reverse chronic pulmonary hypertensi on. The failure of infused NO to reduce pulmonary hypertension is expl ained by the fact that the inactivation of NO by haemoglobin is much f aster than anticipated.