Allopurinol-enhanced postischemic recovery in the isolated rat heart involves repletion of high-energy phosphates.
The effects of allopurinol (AP) on functional and metabolic recovery of the isolated rat heart after global ischemia were studied. Hearts were subjected to aerobic perfusion (30 min), cardioplegic infusion (5 min), normothermic ischemia (37 min), and reperfusion (50 min) which was started with secondary cardioplegic infusion (10 min). AP was injected into rats (44 mg/kg body wt ip 2 h before heart excision) and added to cardioplegic solution (2 mM) prior and after ischemia. AP treatment significantly improved postischemic recovery of the function and reduced the leakage of lactate dehydrogenase from reperfused hearts. These beneficial effects were accompanied by a better preservation of tissue content of ATP, the total adenine nucleotides, phosphocreatine, and the total creatine at the end of reperfusion. Inhibition of xanthine oxidase by AP substantially decreased pre- and postischemic release of xanthine and uric acid and increased postischemic release of hypoxanthine into the coronary effluent. Despite this, AP-treated hearts did not exhibit a reduction in hydroxyl radical adduct formation in the effluents at reperfusion assessed by the spin-trap measurements. The results suggest that AP may protect the heart from ischemia/reperfusion injury due to enhanced energy provision rather than by prevention of oxygen-derived free radical formation.
Pisarenko
O I
OI
Institute of Experimental Cardiology, Academy of Medical Sciences, Moscow, Russia.
Lakomkin
V L
VL
Studneva
I M
IM
Timoshin
A A
AA
Kuzmin
A I
AI
Ruuge
E K
EK
Kapelko
V I
VI
D000244:Adenosine Diphosphate / Q000032:analysis; D000249:Adenosine Monophosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D005609:Free Radicals; D006321:Heart / Q000187:drug effects*; D006334:Heart Function Tests; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D005609:Free Radicals; D010710:Phosphates; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000493:Allopurinol; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D014969:Xanthine Oxidase