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Published ahead of print on March 5, 2003, doi:10.1164/rccm.200208-963OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 11, June 2003, 1540-1547

A more recent version of this article appeared on June 1, 2003
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Submitted on September 3, 2002
Accepted on March 1, 2003

Respiratory Effects of Gestational Intermittent Hypoxia in the Developing Rat

David Gozal1*, Stephen R Reeves1, Barry W Row2, Jennifer J Neville2, Shang Z Guo2, and Andrew J Lipton2

1 Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville School of Medicine, Louisville, KY, USA; Pharmacology and Toxicology, Kosair Children's Hospital Research Institute, University of Louisville School of Medicine, Louisville, KY, USA, 2 Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville School of Medicine, Louisville, KY, USA

* To whom correspondence should be addressed. E-mail: david.gozal{at}louisville.edu.

Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea, occurs frequently during pregnancy. We hypothesized that IH leads to persistent post-natal changes in respiratory responses to acute hypoxia and adverse effects on spatial function. Time-pregnant Sprague Dawley rats were exposed to IH (IHRA; 21% and 10% O2 alternations every 90 sec) or to normoxia (RARA) until delivery. Ventilatory and metabolic responses to a 20-min acute hypoxic challenge (10% O2) were conducted at post-natal ages 5-30 days. In addition, spatial task learning was assessed in the Morris water maze at 1 and 4 months. Normoxic ventilation was higher at all time points in IHRA rats (p<0.01). Peak hypoxic ventilatory responses (pHVR) were attenuated in IHRA at 5-days of age and hypoxic ventilatory depression (HVD) was accentuated at this age. However, ventilatory equivalents (minute ventilation/oxygen consumption) revealed significant reductions in IHRA at pHVR and HVD at all post-natal ages (p<0.01). Acquisition and retention of a spatial task were similar in the 2 groups at both 1 and 4 months of age. We conclude that gestational intermittent hypoxia elicits long-lasting alterations in respiratory control. We postulate that such IH-induced respiratory plasticity may create selective vulnerability to hypoxia during development.
Key words: sleep, intermittent hypoxia, obstructive sleep apnea, cognitive impairment, memory, water maze, hypoxic ventilatory response




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