Metabolite changes in the loaded hypoperfused and failing diaphragm

Metabolite changes in the costal diaphragm were determined in anesthetized dogs subjected to a moderate inspiratory elastic load and to reduced blood flow. Diaphragmatic blood flow was reduced by occlusion of the descending aorta and internal mammary arteries. The goal of this study was to demonstrate that the failing diaphragm under these conditions shows biochemical changes similar to that of skeletal muscle fatigue. Selected metabolite concentrations were determined 1) during mechanical ventilation and normal blood flow, 2) during blood flow reduction and inspiratory loading when the ratio of airway pressure to diaphragmatic electromyogram (Paw/Edi) had decreased by 50% (fatigue), and 3) at 1 h after restoration of blood flow and mechanical ventilation (recovery). During fatigue, glycogen, ATP, and phosphocreatine were 30, 50, and 50% of control levels, respectively. Glucose 6-phosphate and lactate were two- and fivefold higher, respectively, than control concentrations. During recovery, all metabolites, except ATP and lactate, returned to control concentrations. These changes were not seen in resting ischemic skeletal muscles or in the diaphragmatic samples of the mechanically ventilated animals with diaphragmatic blood flow limitation. We conclude that when the loaded and hypoperfused diaphragm fails, as indicated by lower than control Paw/Edi, metabolite changes similar to that observed in fatigued skeletal muscle occur.