Comparative Responses of Premature Versus Full-Term Newborn Rats to Prolonged Hyperoxia

Abstract

ABSTRACT. Because fetal rat lungs have lower baseline levels of both surfactant and antioxidant enzymes than fullterm newborn rats, we questioned whether prematurely delivered rats might be more susceptible to 0 2 toxicity than those born a t term. In the present studies, prematurely delivered rats (gestational d 21 of 22) and full-term rat pups were simultaneously put in >95% O 2 after birth. Surprisingly, we found that the preterm rats were not more susceptible to 02-induced lung damage and lethality than full-term newborns, but, in fact, the composite percentage of survival was even greater in the preterm pups from 7 to 9 d in hyperoxia and were similar thereafter up to 14 d in high 02. In addition, the preterm rats showed significantly decreased lung wetidry weight ratios and consistently less severe pathologic evidence of pulmonary edema compared with term rats at 6 and 8 d of 0 2 exposure. The premature pups demonstrated the capability of inducing pulmonary antioxidant enzyme responses to hyperoxia by 3 d, and had significantly elevated copper-zinc superoxide dismutase, catalase, and glutathione peroxidase activities (and lung surfactant contents) a t 6 d of 0 2 exposure compared with the term rats in 02. The rates of lung total O 2 consumption and cyanide-resistant 0 2 consumption a t d 6 in hyperoxia were not different for preterm versus term pups. Although the basis for the transiently improved survival and decreased evidence of pulmonary 0 2 toxicity in the preterm rats is presently unknown, these findings clearly indicate that premature animals of a t least one species are equally able to induce protective lung antioxidant enzymes and surfactant responses to hyperoxia a s full-term newborn animals. Neonatal animals of many species are relatively resistant to pulmonary oxygen toxicity and lethality when compared with adult animals of the same species ( 1 ). This relative 0 2 tolerance is manifested by much longer survival in hyperoxia and is associated with the induction of increased lung AOE (superoxide dismutase, catalase, and glutathione peroxidase) activities during O2 exposure (1). Augmented AOE activity levels have been consistently associated with protection from hyperoxic exposure, 7and conversely. the failure to increase protective AOE activities during high O2 challenge usually results in susceptibility to severe 02-induced lung damage (and lethality) (2-4).Because fetal rats have lower baseline levels of both surfactant and pulmonary AOE compared with full-term newborn rats (5). we questioned whether premature rats might be more susceptible to O2 toxicity than those born at term. T o answer this experimental question, which to date has been previously explored in only two other species (rabbit and guinea pig). we performed studies in which term-newborn and prematurely delivered rats were simultaneously exposed to prolonged hyperoxia. Comparative AOE and surfactant responses to Oz challenge were determined. as were comparative assessments of 02-induced lung damage. The findings herein indica...

Hyperoxia Causes Inducible Nitric Oxide Synthase-Mediated Cellular Damage to the Immature Rat Brain

“…Exposure to high oxygen concentrations has long been known to cause pulmonary morbidity (21,27,28). It has been shown that hyperoxia serves as a potent trigger of upregulation of iNOS mRNA expression in pulmonary cells within several hours of oxygen exposure in mice (29) as well as in rats (30).…”

Positive Regulation of Pulmonary Antioxidant Enzyme Gene Expression by Prenatal Thyrotropin Releasing Hormone Plus Dexamethasone Treatment in Premature Rats Exposed to Hyperoxia

“…Some nonexperimental full-term newborn rat pups (marked by tail snip) were added at 24 hand/or 48 h of exposure when necessary to readjust the litter sizes to 10-12 pups per dam to ensure equal litter sizes for equivalent nutrition. The details of the procedures and conditions of hyperoxic exposures have been previously described (7). Survival was noted daily during the 14-d exposure period.…”

“…Randomly selected 0z-exposed and air-exposed pups from each group were killed by an intraperitoneal overdose of pentobarbital after either 2 or 7 d of exposure. The procedures of lung perfusion have been previously described (7). The left lungs of two pups were pooled for measuring AOE mRNA concentrations; the right lungs of the same pups were pooled for assaying AOE activities.…”

Premature Rats Treated with Propylthiouracil Show Enhanced Pulmonary Antioxidant Enzyme Gene Expression and Improved Survival during Prolonged Exposure to Hyperoxia

“…Some nonexperimental full-term newborn rat pups (marked by tail snip) were added at 24 h and/or 48 h of exposure when necessary to readjust the litter sizes to 12 pups per dam to ensure equal litter sizes for equivalent nutrition. The procedures and conditions of hyperoxic exposures were as previously described (5). Survival was noted daily during the 14-d exposure period.…”

“…Randomly selected 0,-exposed and air control pups from each group were killed by an intraperitoneal overdose of pentobarbital after 7 d of exposure. The procedures of lung perfusion were as previously described (5). The left lungs were used for measuring AOE mRNA concentrations, and the right lungs of the same pups were used for assaying AOE activities.…”