Aims: 

Chronic hypoxia (CH) is common in respiratory disease and occurs in healthy individuals at altitude. CH alters skeletal muscle structure and oxidative capacity. The aim of this study was to examine the effects of CH on diaphragm muscle contractile function.

Methods: 

Adult male Wistar rats were exposed to hypobaric hypoxia (barometric pressure = 380mmHg) for 6 weeks (n = 6). Age-matched control rats (n = 6) were housed in normobaric conditions. At the end of the treatment periods, isometric contractile properties of isolated strips of diaphragm muscle were measured in tissue baths under hyperoxic (95%O₂/5%CO₂) or hypoxic (95%N₂/5%CO₂) conditions. Force-frequency relationship was determined in response to supra-maximal stimulation (10-100Hz, 300msec). Fatigue was assessed in response to repeated tetanic contractions (40Hz, 300msec) every 2 sec for 5 minutes.

Results: 

CH exposure was confirmed by evidence of elevated haematocrit and right ventricular hypertrophy compared to control rats. Peak tetanic force at 100Hz was reduced following CH but this did not achieve statistical significance (20.0 ± 2.4 vs. 14.2 ± 1.8 N/cm², control vs. hypoxia). The fatigue index (ie ratio of force at 5 min of fatigue to initial force) was significantly altered by CH (32.5 ± 4.8 vs. 51.7 ± 3.2*; % of initial force, control vs. CH, P < 0.05). Under in vitro hypoxic conditions diaphragm muscle force was significantly reduced and muscle endurance was significantly lower than muscles in hyperoxia for both control and CH groups. However, the magnitude of diaphragm fatigue was less in hypoxia for CH muscles.

Conclusions: 

CH causes functional plasticity in diaphragm muscle. CH reduces specific force but increases muscle endurance and hypoxic tolerance. These changes may be potentially adaptive in circumstances of prolonged hypoxaemia.