The effect of ischemia/reperfusion on adenine nucleotide metabolism and xanthine oxidase production in skeletal muscle.

Prolonged ischemia to skeletal muscle as occurs after an acute arterial occlusion results in alterations in adenine nucleotide metabolism. Adenosine triphosphate continues to be used for cellular functions, and an ischemia-induced degradation of phosphorylated adenine nucleotides is initiated. In this experiment we demonstrated the time-dependent aspect of adenine nucleotide depletion during ischemia and the production of large quantities of soluble precursors. In addition, we studied the rate of conversion of xanthine dehydrogenase to xanthine oxidase, a potential source of oxygen-free radicals, after controlled periods of total normothermic ischemia (4 hours and 5 hours) and during the reperfusion phase. During ischemia complete depletion of creatine phosphate occurred in both groups, and adenosine triphosphate fell from 22.1 +/- 1.3 to 10.3 +/- 1.4 mumol/gm dry weight after 4 hours and from 21.6 +/- 0.7 to 3.9 +/- 0.8 mumol/gm dry weight after 5 hours (p less than 0.05). During reperfusion, creatine phosphokinase resynthesis occurred in both groups, but adenosine triphosphate levels were not significantly increased (p greater than 0.05). A washout of lipid soluble products of adenine nucleotide metabolism occurred equally in both groups. The relationship between phosphorylated adenine nucleotides as measured by the energy charge potential fell significantly in both groups (p less than 0.05), but after the shorter period of ischemia (4 hours it returned to normal during early reperfusion but did not after 5 hours of ischemia. There was 21% +/- 4% necrosis after 4 hours and 51% +/- 8% after 5 hours of ischemic stress when assessed at 48 hours. In conclusion, the degree of adenine nucleotide degeneration as determined primarily by the length of the ischemic period, may be the most important determinant of the ultimate extent of skeletal muscle ischemic necrosis that results from an acute interruption of circulation.