The influence of vitamin E and dihydrolipoic acid on cardiac energy and glutathione status under hypoxia-reoxygenation.

The combination of vitamin E supplementation with dihydrolipoic acid perfusion synergistically improves cardiac functional recovery during post-ischemic reperfusion or post-hypoxic reoxygenation of the rat heart. To elucidate the mechanism of this effect, isolated rat hearts were perfused using a working heart system. In hearts perfused with a buffer containing dihydrolipoic acid, ATP levels were significantly higher than those of hearts perfused without addition of dihydrolipoic acid during 90 min of reoxygenation following 30 min of hypoxia. Cardiac tissue glutathione status measured in hearts after perfusion experiments showed significant elevation of reduced glutathione in vitamin E supplemented normoxic rat hearts without hypoxia. Significant elevation of oxidized glutathione was observed in dihydrolipoic acid perfused heart after hypoxia-reoxygenation. It is concluded that vitamin E and dihydrolipoic acid exert separate and synergistic effects in the protection of the hypoxic-reoxygenated heart.

Cardiac recovery during post-ischemic reperfusion is improved by combination of vitamin E with dihydrolipoic acid.

Effects of dietary vitamin E supplementation in rats were studied to determine whether or not they have a higher tolerance against cardiac ischemia-reperfusion injury using the working or Langendorff heart systems. Also, dihydrolipoic acid, recently reported to have potent antioxidant properties and accelerate vitamin E recycling of membrane in vitro, was perfused into the heart model systems to investigate its in vivo relationship with vitamin E. Tissue vitamin E content was increased by vitamin E feeding, but heart preparations did not show any improved functional recovery. Control hearts perfused with dihydrolipoic acid also did not show any improvement. However, a synergistic response is observed with the combination of dihydrolipoic acid perfusion and high dietary vitamin E using both perfusion systems in improvement of cardiac recovery. These results indicate that a high concentration of myocardial vitamin E does not increase tolerance to ischemia-reperfusion injury by itself, but, the combination of exogenous dihydrolipoic acid and high endogenous vitamin E can produce synergistic protective effects on recovery from ischemia during reperfusion.

Cardioprotective efficiency of dihydrolipoic acid in working rat hearts during hypoxia and reoxygenation. 31P nuclear magnetic resonance investigations.

The working rat heart model was used for 31P nuclear magnetic resonance (NMR) studies during normoxia, hypoxia and reoxygenation. Aortic flows of about 35 ml/min could be achieved which equals 65% of the values obtained outside the NMR magnet. Addition of dihydrolipoic acid (DHL) at a concentration of 0.3 mumol/l during hypoxia accelerated the recovery of aortic flow and stabilized it during reoxygenation. During hypoxia, inorganic phosphate contents (Pi) were significantly higher in controls. The phosphate shift indicated a pH decrease in control to 6.98, in DHL treated hearts the calculated pH was 7.15. During both hypoxia and reoxygenation, the phosphocreatinine (PCr) contents were higher in the DHL treated hearts than in controls. In the controls, saturation 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 increased. 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) conditions in the presence of 0.7 nmol DHL per mg of protein. At higher concentrations of DHL, creatine kinase activity was increased under all conditions. An increase in ATP synthesis in the working rat heart under influence of DHL is corroborated by NMR spectroscopy.

Generation of free radicals in Langendorff and working hearts during normoxia, hypoxia, and reoxygenation.

The release of .OH and alkyl free radicals into the coronary flow were compared in Langendorff perfused and working rat hearts during normoxia (30 min), hypoxia (30 min) and reoxygenation (60 min) by means of spin-trapping techniques using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO). In Langendorff hearts, there was a small but steady increase in the radical concentration during the course of hypoxia and reoxygenation. At the start of reoxygenation, only small initial peaks of hydroxyl and alkyl radicals occurred. After a general decrease of free radical production during hypoxia, working hearts produced nearly double the amount of free radicals during reoxygenation as Langendorff hearts. After an initial large increase during early reoxygenation, the amount of free radicals produced fluctuated on a high level during the remaining reoxygenation period. Heart work is thus correlated with an increased production of free radicals, possibly due to an increase in oxygen consumption by the heart.