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Physiol Rep. 2014 May 28;2(5). pii: e12023. doi: 10.14814/phy2.12023. Print 2014 May 1.

Maternal nicotinic exposure produces a depressed hypoxic ventilatory response and subsequent death in postnatal rats.

Author information

1
Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico.

Abstract

In this study, we asked whether a "full term" prenatal nicotinic exposure (fPNE, 6 mg·kg(-1)·day(-1) nicotinic delivery) over the full gestation, compared to a traditional PNE (tPNE) over the last two-thirds of the gestation, caused a higher mortality following a remarkable depressed hypoxic ventilatory response (dHVR) independent of brain and pulmonary edema and change in serum corticosterone. P12-14 pups pretreated with tPNE, fPNE or their vehicle (tCtrl and fCtrl) were exposed to 5% O2 for up to 60 min followed by harvesting the brain and lungs or anesthetized to collect blood for detecting arterial blood pH/gases and serum cotinine and corticosterone levels. We found that fPNE had little effect on baseline VE and heart rate, but consistently induced a dHVR and prolonged apnea that were rarely observed after tPNE. The severity of the dHVR in PNE pups were closely correlated to an earlier appearance of lethal ventilatory arrest (the hypoxia-induced mortality). PNE did not induce brain and pulmonary edema, but significantly increased serum corticosterone levels similarly in tPNE and fPNE pups. Moreover, the accumulated nicotinic dose given to the individual was significantly higher in fPNE than tPNE pups, though there was no difference in serum cotinine levels and arterial blood pH/gases between the two groups. Our results suggest that nicotinic exposure at the early stage of gestation achieved by fPNE, rather than tPNE, is critical in generating the dHVR and subsequent death occurring independently of brain/pulmonary edema and changes in arterial blood pH/gases and serum corticosterone.

KEYWORDS:

Cardiorespiratory failure; cotinine; hypoxemia; maternal cigarette smoking; sudden infant death syndrome

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