Cimetidine reduces acute hyperoxic lung injury in lambs. Injury reduction appears to be due to inhibition of P450 activity in lung and a consequent decrease in release of free-radical oxidants by isoforms of this enzyme system that are induced by increased O2 tension (JAP 67:2486, 1989; JCI 96:2083, 1995). To determine whether cimetidine might have a similar beneficial effect in newborn premature infants at risk for bronchopulmonary dysplasia, we used a mass spectrometic assay to measure F2-isoprostane levels in tracheobronchial aspirate fluid (TBAF) before and after giving a 24-hour i.v. infusion of cimetidine (0.5 mg/kg/h) to 6 NICU patients receiving mechanical ventilation. F2-isoprostanes (F2I) are free-radical catalyzed metabolites of arachidonic acid which are produced independent of cyclooxygenase and which have been shown to be a highly sensitive and specific marker of lipid peroxidation in vivo. Study patients had a birth weight of 1170 ±468 g, and were 88 ±42 h postnatal age and receiving an FIO2 of 0.43 ±0.15 when the cimetidine infusion began. Five of the 6 patients had detectable F2I in TBAF before cimetidine. F2I levels decreased significantly in all 5 of these patients from 33 (18-405) pg/mL (median, range) to 17 (0-100) (P=0.043, Wilcoxon signed ranks test) without a significant change in FIO2 (P=0.686). The average decrease following cimetidine was 58 ±35% of baseline. The patient with the lowest detectable F2I level had the smallest decrease (8%). Since cimetidine is not known to have intrinsic anti-oxidant properties, these results support the hypothesis that P450 is a significant source of free-radical oxidants in the lungs of premature newborn infants and that blockade of P450 with cimetidine will reduce oxidant-induced lung injury.

(Supported by NIH Pediatric Pulmonary SCOR HL-14214)

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cotton, R., Hazinski, T., Morrow, J. et al. EFFECT OF CIMETIDINE ON LIPID PEROXIDATION IN THE LUNGS OF PREMATURE NEWBORN INFANTS. † 1956. Pediatr Res 39, 329 (1996). https://doi.org/10.1203/00006450-199604001-01980

Download citation

Further reading