CARDIOPROTECTIVE EFFICIENCY OF DIHYDROLIPOIC ACID IN WORKING RAT HEARTS DURING HYPOXIA AND REOXYGENATION - P-31 NUCLEAR-MAGNETIC-RESONANCE INVESTIGATIONS

The working rat heart model was used for P-31 nuclear magnetic resonan ce (NMR) studies during normoxia, hypoxia and reoxygenation. Aortic fl ows of about 35 ml/min could be achieved which equals 65 % of the valu es obtained outside the NMR magnet. Addition of dihydrolipoic acid (DH L) at a concentration of 0.3 mumol/l during hypoxia accelerated the re covery of aortic flow and stabilized it during reoxygenation. During h ypoxia, inorganic phosphate contents (P(i)) were significantly higher in controls. The phosphate shift indicated a pH decrease in control to 698, in DHL treated hearts the calculated pH was 7.15. During both hy poxia and reoxygenation, the phosphocreatine (PCr) contents were highe r in the DHL treated hearts than in controls. In the controls, saturat ion transfer measurements revealed a decrease of the flux PCr --> ATP during initial reoxygenation, whereas after addition of 0.3 mumol/l of DHL during hypoxia creatine kinase flux remained constant or increase d In isolated rat heart mitochondria, creatine kinase activities were measured under saturating and non-saturating concentrations of PCr An increase in activity was observed under low PCr (non-saturating) condi tions in the presence of 0.7 nmol DHL per mg of protein. At higher con centrations of DHL, creatine kinase activaty was increased under all c onditions. An increase in ATP synthesis in the working rat heart under influence of DHL is corroborated by NMR spectroscopy.