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.