Metabolic response of skeletal muscle to ischemia.
To evaluate the temporal relationship and potential correlation between intramuscular phosphagen levels, lipid oxidation, and extent of muscle injury, a canine gracilis muscle model was used to study the consequences of a global ischemic episode for up to 7 h duration with reperfusion for 4 h. In this model the contralateral gracilis muscle was prepared identically to the test side but was not subjected to ischemia and thus served as a control. Blood flow, oxygen consumption, and lactate and glycerol release were measured before and after 2- and 7-h ischemic stress periods. The intramuscular metabolites, glycogen, lactate, phosphocreatine, and ATP, as well as free fatty acid conjugated dienes, were measured before, during, and after the ischemic insult. A 2-h ischemic insult resulted in minimal ultrastructural damage and complete regeneration of intramuscular phosphagens and glycogen on reperfusion with complete normalization of lipid oxidation products. In contrast, a 7-h ischemic insult resulted in profound injury at the ultrastructural level with an inability to restore intramuscular phosphagens and glycogen on reperfusion. This severe muscle injury correlated with a 2.5-fold increase in lipid oxidation products (free fatty acid conjugated dienes) and a decline in ATP levels below 5 mumol/g dry wt on reperfusion. Our results emphasize the prolonged glycolytic activity of skeletal muscle during global ischemia and document the increased production of oxygen free radical-mediated lipid oxidation products in irreversibly injured muscle.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008054:Lipid Peroxides / Q000378:metabolism; D008854:Microscopy, Electron; D009132:Muscles / Q000098:blood supply* / Q000648:ultrastructure; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D012039:Regional Blood Flow; D013997:Time Factors
D005230:Fatty Acids, Nonesterified; D007773:Lactates; D008054:Lipid Peroxides; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen