Lipoate ameliorates ischemia-reperfusion in animal models.
Ischemia and reperfusion were studied in isolated working rat hearts and in exarticulated rat hind limbs. Free radicals are known to be generated in ischemia/reperfusion and to propagate complications. To reduce reperfusion injury, conditions were ameliorated including the treatment with antioxidants, lipoate or dihydrolipoate. In isolated working rat hearts, cardiac and mitochondrial parameters are impaired during hypoxia and partially recover in reperfusion. Dihydrolipoate, if added into the perfusion buffer at 0.3 microM concentration, keeps the pH higher (7.15) during hypoxia, as compared to controls (6.98). This compound accelerates and stabilizes the recovery of the aortic flow. With dihydrolipoate, ATP synthesis is increased, ATPase activity (ATP hydrolysis) reduced, intracellular creatine kinase activity maintained and thus phosphocreatine contents are higher than in controls. For exarticulated rat hind limbs, the dihydrolipoate group contained 8.3 microM in the modified reperfusate. Recovery of the contractile function was 49% vs. 34% in controls and muscle flexibility was maintained whereas it decreased by 15% in the controls. Release of creatine kinase from cells was significantly lower with dihydrolipoate. Lipoate/dihydrolipoate effectively reduced reperfusion injury in isolated working rat hearts and in exarticulated rat hind limbs after extended ischemia. Finally, the compound was successfully applied in an in vivo pig hind limb model.
Freisleben
H J
HJ
Faculty of Medicine, University of Indonesia, Jakarta. freisleben@centrin.net.id
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001013:Aorta, Thoracic; D015687:Cell Hypoxia; D003250:Constriction; D003402:Creatine Kinase / Q000032:analysis; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006614:Hindlimb / Q000098:blood supply*; D007083:Iliac Artery; D007511:Ischemia / Q000150:complications / Q000188:drug therapy*; D007527:Isoenzymes / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009124:Muscle Proteins / Q000032:analysis; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D018384:Oxidative Stress; D010725:Phosphocreatine / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D013552:Swine; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000975:Antioxidants; D016166:Free Radical Scavengers; D007527:Isoenzymes; D009124:Muscle Proteins; D010725:Phosphocreatine; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D000255:Adenosine Triphosphate; D003402:Creatine Kinase