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Am J Physiol Regul Integr Comp Physiol 290: R1664-R1671, 2006. First published February 2, 2006; doi:10.1152/ajpregu.00851.2005
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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Early postnatal chronic intermittent hypoxia modifies hypoxic respiratory responses and long-term phrenic facilitation in adult rats

Stephen R. Reeves,1,2 Gordon S. Mitchell,3 and David Gozal1,2

1Departments of Pediatrics and 2Pharmacology and Toxicology, Kosair Children’s Hospital Research Institute, University of Louisville School of Medicine, Louisville, Kentucky; and 3Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin

Submitted 5 December 2005 ; accepted in final form 27 January 2006

Acute isocapnic intermittent hypoxia elicits time-dependent, serotonin-dependent enhancement of phrenic motor output in anesthetized rats (phrenic long-term facilitation, pLTF). In adult rats, pLTF is enhanced by chronic intermittent hypoxia (CIH). To test the hypothesis that early postnatal CIH induces persistent modifications of ventilation and pLTF, we exposed male Sprague-Dawley rat pups on their first day of life to a CIH profile consisting of alternating room air and 10% oxygen every 90 s for 30 days during daylight hours (RAIH) or to comparable exposures consisting of room air throughout (RARA). One month after cessation of CIH, respiratory responses were recorded using whole body plethysmography, and integrated phrenic nerve activity was recorded in urethane-anesthetized, vagotomized, paralyzed, and ventilated rats at baseline and after exposures to three 5-min hypoxic episodes [inspired O2 fraction (FIO2) = 0.11] separated by 5 min of hyperoxia (FIO2 = 0.5). RAIH rats displayed greater normoxic ventilation and also increased burst frequency compared with RARA rats (P < 0.01). Ventilatory responses to hypoxia and short-term phrenic responses during acute hypoxic challenges were reduced in RAIH rats (P < 0.01). Although pLTF was present in both RAIH and RARA rats, it was diminished in RAIH rats (minute activity: 74 ± 2% in RARA vs. 55 ± 5% in RAIH at 60 min; P < 0.01). Thus we conclude that early postnatal CIH modifies normoxic and hypoxic ventilatory and phrenic responses that persist at 1 mo after cessation of CIH (i.e., metaplasticity) and markedly differ from previously reported increased neural plasticity changes induced by CIH in adult rats.

respiratory control; development; plasticity; metaplasticity


Address for reprint requests and other correspondence: D. Gozal, Kosair Children’s Hospital Research Institute, Univ. of Louisville, Suite 204, 570 South Preston St., Louisville, KY 40202 (e-mail: david.gozal{at}louisville.edu)




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