Hemolysis‐induced pulmonary hypertension and treatment with infused or inhaled nitrite, or inhaled NO in the newborn lamb

Abstract

BackgroundNO is a tonic vasodilator in the lung. Plasma‐free hemoglobin scavenges NO, resulting in pulmonary vasoconstriction. Oxidized hemoglobin, produced by the reaction of NO with oxyhemoglobin, does not scavenge NO. We hypothesized that NO, administered as a gas (iNO) or as nitrite that is endogeneously converted to NO, would attenuate pulmonary hypertension caused by hemolysis.MethodsIntravenous hemolyzed blood was administered to newborn lambs for 180 min while measuring pulmonary arterial pressure and flow. Changes in pulmonary and systemic pressures and resistances were measured. During the final 90 min of hemoglobin infusion, intravenous nitrite, nebulized nitrite, or iNO (20ppm) were administered.ResultsHemolyzed blood resulted in a significant increase in pulmonary (p<0.01) but not systemic vascular resistance that was sustained throughout the first 90 min of hemolysate infusion. iNO resulted in a rapid return of pulmonary vascular resistance to baseline levels, associated with nearly complete oxidation of plasma hemoglobin (p<0.01). Inhaled nitrite resulted in a significant increase in exhaled NO gas, and a significant decrease in pulmonary vascular resistance. Intravenous nitrite did not alter pulmonary vascular resistance significantly.ConclusionsHemolyzed blood causes selective pulmonary hypertension. Inhaled nitrite produces vasoactive amounts of NO. The benefits of iNO therapy for treatment of hemolysis‐induced pulmonary hypertension may result from both direct vasodilation as well as oxidation of the plasma free hemoglobin to methemoglobin, which does not scavenge NO.