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Postnatal development of metabolic rate during normoxia and acute hypoxia in rats: implication for a sensitive period

Department of ¹Cell Biology, Neurobiology, and Anatomy, and ²Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 24 July 2008 ; accepted in final form 30 December 2008

Previously, we reported that the hypoxic ventilatory response (HVR) in rats was weakest at postnatal day (P) P13, concomitant with neurochemical changes in respiratory nuclei. A major determinant of minute ventilation (E) is reportedly the metabolic rate [O₂ consumption (O₂) and CO₂ production (CO₂)]. The present study aimed at testing our hypothesis that daily metabolic rates changed in parallel with ventilation during development and that a weak HVR at P13 was attributable mainly to an inadequate metabolic rate in hypoxia. Ventilation and metabolic rates were monitored daily in P0–P21 rats. We found that 1) ventilation and metabolic rates were not always correlated, and E/O₂ and E/CO₂ ratios were not constant during development; 2) metabolic rate and E/O₂ and E/CO₂ ratios at P0–P1 were significantly different from the remaining first postnatal week in normoxia and hypoxia; 3) at P13, metabolic rates and E/O₂ and E/CO₂ ratios abruptly increased in normoxia and were compromised in acute hypoxia, unlike more stable trends during the remaining second and third postnatal weeks; and 4) the respiratory quotient (CO₂/O₂) was quite stable in normoxia and fluctuated slightly in hypoxia from P0 to P21. Thus our data revealed heretofore unsuspected metabolic adjustments at P0–P1 and P13. At P0–P1, ventilation and metabolic rates were uncorrelated, whereas at P13, they were closely correlated under normoxia and hypoxia. The findings further strengthened the existence of a critical period of respiratory development around P13, when multiple physiological and neurochemical adjustments occur simultaneously.

carbon dioxide production; critical period; oxygen consumption; respiratory quotient; ventilation