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.
Gustav-Embden-Zentrum der Biologischen Chemie, Universität, Frankfurt, Fed. Rep. of Germany.
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H
Assadnazari
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Zimmer
H J
HJ
Freisleben
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W
Werk
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Leibfritz
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000503:physiopathology / Q000517:prevention & control*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology; D010100:Oxygen / Q000494:pharmacology; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D007202:Indicators and Reagents; D010710:Phosphates; D010725:Phosphocreatine; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D010100:Oxygen