Proceedings of The Physiological Society

University of Manchester (2010) Proc Physiol Soc 19, PC25

Poster Communications

Chronic intermittent hypoxia induces respiratory muscle dysfunction in neonatal rats.

R. A. O'Connell1, K. D. O'Halloran1

1. University College Dublin, Dublin, Ireland.

Infants can experience intermittent bouts of hypoxia (IH) as a consequence of several neonatal respiratory disorders, such as apnoea of prematurity and childhood obstructive sleep apnoea (OSA). It is known that the neonatal respiratory system is subject to considerable developmental plasticity and certain insults, such as hypoxia, during critically vulnerable periods of development can ultimately induce persistent maladaptive changes. It has been established that IH induces muscle dysfunction in adult animal models of OSA. Therefore, in this study we sought to investigate the effects of chronic IH on respiratory muscle function during early development. Wistar rat litters together with their dams were placed from birth in hypoxia chambers with automated control of chamber O2 concentration. The IH litter 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 litter was exposed to circulating normoxic gas in one of the chambers. After 1 week, half of the control and CIH litters were killed humanely under 5% isoflurane. The sternohyoid (pharyngeal dilator) muscle and the diaphragm were removed and isometric contractile and endurance properties of the isolated muscle strips were examined in tissue baths containing physiological salt solution (PSS) at 35°C. The remaining half of both litters were left to recover in normoxia for a further week, before functional studies were performed on the respiratory muscles. CIH resulted in a significant decrease in sternohyoid and diaphragm muscle force. Peak force following control and CIH treatment was, 5.0±1.5 N/cm2 and 1.2±0.1 N/cm2 in the sternohyoid (n=4, P<0.05, ANOVA) and 14±1 N/cm2 and 9±1 N/cm2 in the diaphragm (n=4, P<0.05), respectively. There was a partial recovery of sternohyoid force in CIH-treated animals (8±1 N/cm2 and 5±1 N/cm2, control and CIH respectively) after 1 week recovery in normoxia. However, the depression of diaphragm peak force following CIH persisted one week after treatment. CIH caused a significant improvement in sternohyoid muscle endurance that declined following the period of recovery. Conversely, CIH had no effect on diaphragm fatigue. In summary, CIH had a deleterious effect on respiratory muscle force. Furthermore, CIH improved sternohyoid, but not diaphragm, endurance. As the functional activity of the respiratory muscles is essential for adequate ventilation we suggest that respiratory muscle weakness will have detrimental effects on performance and hence respiratory homeostasis. Such maladaptation could exacerbate and perpetuate neonatal respiratory disorders.

Where applicable, experiments conform with Society ethical requirements