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Respiratory Effects of Gestational Intermittent Hypoxia in the Developing Rat

Department of Pediatrics and Department of Pharmacology and Toxicology, Kosair Children's Hospital Research Institute, University of Louisville School of Medicine, Louisville, Kentucky

Correspondence and requests for reprints should be addressed to Dr. David Gozal, M.D., Kosair Children's Hospital Research Institute, University of Louisville, 570 S. Preston Street, Ste. 321, Louisville, KY 40202. E-mail: david.gozal{at}louisville.edu

Intermittent hypoxia (IH), one of the hallmarks of obstructive sleep apnea, occurs more frequently during pregnancy. We hypothesized that IH may lead to persistent postnatal changes in respiratory responses to acute hypoxia and may also lead to adverse effects on spatial function learning as revealed by the Morris water maze. To examine this issue, time-pregnant Sprague-Dawley rats were exposed to IH and room air (IHRA; 21 and 10% O₂ alternations every 90 seconds) or to normoxia (RARA) until delivery. Ventilatory and metabolic responses to a 20-minute acute hypoxic challenge (10% O₂) were conducted at postnatal ages 5, 10, 15, and 30 days. In addition, spatial task learning was assessed in the water maze at 1 and 4 months of age. Normoxic ventilation was higher at all time points in IHRA rats than in RARA rats (p < 0.01). Peak hypoxic ventilatory responses were attenuated in IHRA rats at 5 days of age and hypoxic ventilatory depression was accentuated at this age as well. However, ventilatory equivalents (minute ventilation/oxygen consumption) revealed significant reductions in peak hypoxic ventilatory responses of IHRA rats and hypoxic ventilatory depression at all postnatal ages (p < 0.01). Acquisition and retention of a spatial task were similar in the IHRA and RARA groups at both 1 and 4 months of age. We conclude that gestational intermittent hypoxia elicits long-lasting alterations in the control of breathing. We postulate that such IH-induced respiratory plasticity may create selective vulnerability to hypoxia during development.

Key Words: cognitive impairment • hypoxic ventilatory response • memory • obstructive sleep apnea • water maze

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