Proceedings of The Physiological Society
University of Birmingham (2010) Proc Physiol Soc 20, PC34
Ventilatory effects of chronic intermittent hypoxia in the rat.
D. Edge1, K. D. O'Halloran1
1. School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
Sleep-disordered breathing (SDB) is prevalent and is associated with significant cardiovascular, metabolic and neurocognitive morbidities. Chronic intermittent hypoxia (CIH) is a hallmark feature of SDB due to recurrent pauses in ventilation (apnoea). CIH has been shown to elicit plasticity at multiple levels of the respiratory control system, with reports of both adaptive and maladaptive consequences for respiratory homeostasis. We sought to further characterise the effect of chronic intermittent hypoxia on the control of breathing in unanaesthetised freely-behaving male rats using whole-body plethysmography. Adult male (n=14) Wistar rats were exposed to alternating periods of N2 and air for 90s each, for 8hrs a day for 3 days (CIH) group (5% O2 at nadir; SaO2 ~ 80%). The sham group were subject to alternating cycles of air/air, under identical experimental conditions. Following treatment, baseline normoxic ventilation and ventilatory responses to acute hypoxia (FiO2 = 0.10, 20 mins) and hypercapnia (FiCO2 = 0.05, 10 mins) were assessed. Ventilation following exposure to acute intermittent hypoxia (AIH), consisting of 5 mins hypoxia (FiO2 = 0.10) and 7 mins normoxia (breathing room air) for 10 cycles, was also assessed in both groups. Baseline normoxic ventilation was significantly increased in CIH-treated rats compared to sham animals [57.3 ± 1.7 vs. 71.8 ± 1.8, mean±SEM, VE; ml/min/100g body weight, sham (n=7) vs. CIH (n=7), Student’s t test, p<0.0001]. Neither hypoxic [60 ± 7% vs.45 ± 11%, % change from baseline for sham vs. CIH] nor hypercapnic [73 ± 8% vs.89 ± 15%, % change from baseline, sham vs. CIH] ventilatory responses were affected by 3 days of CIH. Sham animals displayed facilitated breathing immediately following exposure to AIH [57.3 ± 1.7 vs. 61.3 ± 1.5 ml/min/100g before vs. immediately after AIH, Student’s paired t test p = 0.0466]; this persisted for up to one hour post-AIH [66 ± 3.7 ml/min/100g]. Unlike sham animals, CIH-treated animals did not display further enhanced breathing following AIH [71.8 ± 1.8 vs. 70.2 ± 2.3 ml/min/100g]. There was no evidence of enhanced breathing 60min post-AIH in CIH-treated animals [70 ± 4.0 ml/min/100g]. We have shown that CIH - a dominant feature of SDB in humans - significantly affects the respiratory control system increasing normoxic breathing in unanaesthetised rats during quiet rest. CIH did alter hypoxic or hypercapnic ventilatory sensitivity. Long-lasting facilitation of breathing may have maladaptive consequences for respiratory homeostasis.
Where applicable, experiments conform with Society ethical requirements