The protective effect of desferal on rat myocardial mitochondria is not prolonged after withdrawal of desferal.
Reperfusion of ischaemic myocardium is necessary to sustain tissue viability (without it the tissue becomes necrotic), but reperfusion, on the other hand, can damage cells which have survived ischaemia. There is now considerable evidence that oxygen radicals, especially hydroxyl radicals produced via the Haber-Weiss and Fenton reactions, are responsible for reperfusion damage. Various investigators have reported that desferal, an iron chelator, has a beneficial effect on the myocardium during ischaemia and reperfusion. The aim of this study was two-fold: i) whether superoxide anions in the absence of LMWI can impair mitochondrial function, and ii) whether the protective effect of desferal on the mitochondrial function persists after withdrawal of desferal. Experiments were done on isolated rat hearts subjected to normothermic ischaemic cardiac arrest (NICA), with or without desferal, followed by 15-min reperfusion with desferal, followed by 15-min perfusion without desferal, or a hypoxanthine/xanthine oxidase medium that generates superoxide anions (with or without desferrioxamine (desferal) in the perfusate). Mitochondrial function (QO2 (state 3), ADP/O and OPR) as well as LMWI were measured. Our results indicated that i) superoxide anions and/or hydrogen peroxide can, independently of LMWI, damage the mitochondria, and ii) withdrawal of desferal after the respiratory burst resulted in the same or more severe mitochondrial damage than without any desferal.
van Jaarsveld
H
H
Department of Chemical Pathology, University of the Orange Free State, Bloemfontein, Republic of South Africa.
Kuyl
J M
JM
Alberts
D W
DW
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D005609:Free Radicals; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D008970:Molecular Weight; D015425:Myocardial Reperfusion; D010100:Oxygen / Q000494:pharmacology; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D005609:Free Radicals; D000244:Adenosine Diphosphate; D007501:Iron; D003676:Deferoxamine; D010100:Oxygen