Proceedings of The Physiological Society
University of Birmingham (2010) Proc Physiol Soc 20, C14 and PC14
Respiratory muscle weakness following chronic intermittent hypoxia during early development in the rat.
R. A. O'Connell1, K. D. O'Halloran1
1. UCD School of Medicine and Medical Sciences, UCD, Dublin, Ireland.
It is known that the developing respiratory system is subject to considerable developmental plasticity and certain insults during vulnerable periods of development can induce persistent maladaptive changes. The effects of chronic intermittent hypoxia (CIH) on respiratory muscle function during early development are not known but we hypothesize, based on observations in adult animal models of OSA, that CIH during early life may perturb respiratory muscle function, perhaps permanently. Therefore, we sought to investigate the effects of CIH on respiratory muscle force production during early development. Litters of Wistar rats together with their dams were placed from birth in hypoxia chambers. The CIH litters received alternating cycles of 90 sec hypoxia (reaching 5% O2 at the nadir) and 210 sec normoxia (21% O2) for 8hr/day for 7 days. The control litters were exposed to circulating normoxic gas for 7 days. After 1 week, half of the control and CIH litters were killed humanely under 5% isoflurane. The diaphragm and sternohyoid (pharyngeal dilator) muscles were removed and contractile and endurance properties were examined in tissue baths containing physiological salt solution (PSS) at 35oC. The remaining half of both sets of litters were left to recover in normoxia for a further week, before functional studies were performed. CIH-treated rats had a significantly reduced body mass and increased right ventricular mass. CIH caused a significant decrease in sternohyoid and diaphragm isometric twitch force and contraction time (n=8, P<0.05), but had no effect on half-relaxation time. CIH caused a significant depression in the sternohyoid force-frequency relationship; peak force was 4.3±0.8 N/cm2 and 1.6±0.3 N/cm2 in control and CIH-treated muscles, respectively (n=8, P<0.0001). CIH caused a significant decrease in the diaphragm force-frequency relationship; peak force was 13.8±1.0 N/cm2 and 8.6±1.1 N/cm2. There was no significant change in the sternohyoid EF50 values (i.e. stimulus frequency producing 50% of peak force), however CIH significantly increased diaphragm EF50 values; 26±1 Hz and 31±1 Hz in control and CIH-treated rats respectively (n=8, P<0.01). Following 1 week recovery in normoxia, the negative inotropic effect of CIH on sternohyoid and diaphragm force persisted (n=8, P<0.001). In summary, CIH during the first week of life had a substantial negative inotropic effect on rat respiratory muscles, which persisted after a recovery period. CIH-induced respiratory muscle weakness could have detrimental effects on respiratory performance and homeostasis. This may have implications for neonatal respiratory disorders associated with CIH.
Where applicable, experiments conform with Society ethical requirements