Skeletal and respiratory muscle blood flow redistribution during submaximal exercise in pulmonary hypertensive rats

Pulmonary hypertension (PH) is a chronic, progressive disease characterized by pulmonary vascular remodelling, dyspnoea and exercise intolerance. Key facets of dyspnoea and exercise intolerance include skeletal and respiratory muscle contractile and metabolic disturbances; however, muscle perfusion during exercise has not been investigated. We hypothesized that diaphragm blood flow (Q) would be increased and locomotory muscle Q would be decreased during submaximal treadmill running in PH rats compared to healthy controls. Female Sprague-Dawley rats were injected (i.p.) with monocrotaline to induce PH (n = 16), or a vehicle control (n = 15). Disease progression was monitored via echocardiography. When moderate disease severity was confirmed, maximal oxygen uptake (V-O2max) tests were performed. Rats were given >24 h to recover, and then fluorescent microspheres were infused during treadmill running (20 m/min, 10% grade; similar to 40-50% maximal speed attained during the V-O2max test) to determine tissue Q. In PH rats compared with healthy controls, V-O2max was lower (84 (7) vs. 67 (11) ml/min/kg; P < 0.001), exercising diaphragm Q was 35% higher and soleus Q was 28% lower. Diaphragm Q was negatively correlated with soleus Q and V-O2max in PH rats. Furthermore, there was regional Q redistribution in the diaphragm in PH compared to healthy rats, which may represent or underlie diaphragmatic weakness in PH. These findings suggest the presence of a pathological respiratory muscle blood flow steal phenomenon in PH and that this may contribute to the exercise intolerance reported in patients.