Am. J. Respir. Crit. Care Med., Volume 164, Number 5, September 2001, 834-839

Recombinant Human Superoxide Dismutase Enhances the Effect of Inhaled Nitric Oxide in Persistent Pulmonary Hypertension

ROBIN H. STEINHORN, GEORGE ALBERT, DANIEL D. SWARTZ, JAMES A. RUSSELL, CAROLYN R. LEVINE, and JONATHAN M. DAVIS

Department of Pediatrics, Northwestern University, Chicago, Illinois; Department of Pediatrics and Physiology, State University of New York at Buffalo, Buffalo, New York; and Department of Pediatrics and CardioPulmonary Research Institute, Winthrop University Hospital, State University of New York at Stony Brook, Mineola, New York

We investigated the pulmonary vascular effects of superoxide dismutase (SOD) alone and in combination with inhaled nitric oxide (iNO) in newborn lambs with persistent pulmonary hypertension (PPHN) following prenatal ligation of the ductus arteriosus. In in vitro experiments, pretreatment with SOD significantly enhanced vascular relaxation in response to the NO donor S-nitrosyl-acetylpenicillamine (SNAP) in fifth-generation pulmonary arteries isolated from lambs with PPHN. In vivo treatment of fully instrumented newborn lambs with a single intratracheal dose of recombinant human CuZn SOD (rhSOD; 5 mg/kg) produced selective dilation of the pulmonary circulation. Further studies, of the combination of rhSOD and iNO, showed enhancement of the pulmonary vascular effects of iNO after brief periods of inhalation of 5 ppm and 80 ppm NO. We conclude that rhSOD reduces pulmonary vascular resistance and facilitates the action of iNO in a lamb model of PPHN. This suggests that rhSOD may prove to be an effective adjunctive treatment for newborns with PPHN.

Keywords: lung; newborn; pulmonary artery; free radical scavengers

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