Exogenous magnesium chloride-adenosine triphosphate administration during reperfusion reduces the extent of necrosis in previously ischemic skeletal muscle

Abstract

The lower extremity may be exposed to prolonged periods of ischemia, resulting in depletion of intracellular energy stores in the affected skeletal muscle. The role of adenine nucleotide reduction and failure of resynthesis on reperfusion in determining the extent of muscle necrosis was investigated in this study, in addition to the possible beneficial effects of the addition of exogenous adenosine triphosphate-magnesium chloride during early reperfusion. The isolated paired canine gracilis muscle model was used. After 4 hours of normothermic ischemia in group I, a perfusate Krebs-Henseleit solution plus the gradual reintroduction of oxygenated blood flow was compared to standard reperfusion. In group II, a similar infusion protocol was used, with the addition of 2 mmol/L adenosine triphosphate-magnesium choride and compared to normal reperfusion. Adenosine triphosphate-magnesium chloride resulted in the salvage of skeletal muscle, 57% ± 12% versus 44% ± 14% (p < 0.05, n = 6 pairs). Reperfusion with the solution alone increased the resulting necrosis (42% ± 13% vs 60% ± 20%, n = 6 pairs). Adenine nucleotide stores were not increased, but oxygen consumption was increased by magnesium chloride-adenosine triphosphate (p < 0.05, analysis of variance [ANOVA]). A clear relationship was demonstrated between the fall in energy stores, as measured by a change in energy charge potential from preischemia to end ischemia levels, and the extent of resulting necrosis (p < 0.01). In summary, the addition of 2 mmol/L to an infusion of Krebs-Henseleit solution during reperfusion results in significant salvage of skeletal muscle. The fall in intracellular energy stores as measured by change in energy charge potential can accurately predict the resulting extent of muscle necrosis and is not influenced by exogenous magnesium chloride-adenosine triphosphate.