Purine metabolic pathways in rat hindlimb perfusion model during ischemia and reperfusion.
The perfused rat hindlimb preparation was used with a blood cell-free perfusate to investigate alterations in the purine nucleotide metabolism, flow rate, perfusion pressure, and venous excretion in response to ischemia and ischemia followed by reperfusion in skeletal muscle. The development of a physical hindrance during postischemic reperfusion, indicated by an increase in reperfusion pressure and a decrease in flow rate, coincided with a 90% decrease in phosphocreatine and a 50-70% reduction in total adenine nucleotide pool. The reflow impairment could not be explained by blood cell plugging of the capillaries. Washout of several metabolites was demonstrated during reperfusion. Hypoxanthine accumulated intracellularly during ischemia, and a substantial amount of uric acid was excreted into the venous effluent during reperfusion. The experimental data were fitted into a computer simulation model of the purine pathways. The model indicated that AMP deaminase was the predominant enzymatic pathway for the AMP degradation. It was demonstrated that ATP preferably accumulated as inosine-5'-monophosphate during ischemia and that xanthine oxidase was undetectable in skeletal muscle tissue homogenates. However, vascular endothelial cell xanthine oxidase activity responsible for a free radical-induced reperfusion injury could not be excluded.
Soussi
B
B
Wallenberg Laboratory, Department of Surgery, University of Göteborg, Sweden.
Lagerwall
K
K
Idström
J P
JP
Scherstén
T
T
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D003198:Computer Simulation; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D007291:Inosine Monophosphate / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D008954:Models, Biological; D009132:Muscles / Q000378:metabolism; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D011685:Purine Nucleotides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D014969:Xanthine Oxidase / Q000378:metabolism
D000227:Adenine Nucleotides; D011685:Purine Nucleotides; D010725:Phosphocreatine; D007291:Inosine Monophosphate; D014969:Xanthine Oxidase