Electromechanical effects of menadione on isolated rat heart in relation to oxidative stress.
Although Ca2+ overloading has been observed in hepatocytes and in the isolated liver treated with 0.2 mM menadione, it has not been determined if menadione has similar effects on cardiac tissue and, if so, whether Ca2+ overloading leads to cardiac contracture, and if such an event results from plasma membrane peroxidation initiated by oxidative stress. The present study reveals that when the isolated heart is perfused with 0.2 mM menadione for 30 min, it shows Ca2+ overloading, which can not be reversed even after 30 min of drug-free perfusion. The time courses of glutathione, ethane, and LDH release from the hearts do not show a parallel pattern of abnormality between 30 and 60 min, indicating that contractile failure precedes the development of lipid peroxidation or plasma membrane disintegration. The evidence that the plasma membrane of menadione-treated rat cardiac tissue remains intact is supported by the observation that the resting membrane potential of the atrium remains virtually unchanged during the 30 min of drug exposure and then gradually falls (-67 +/- 3.1 vs. -76 +/- 2 mv) only during the last 10 min of the drug washout. Interestingly, even after the atria are treated with menadione for 30 min and followed by washout of 30 min, and have shown calcium overloading, as evidenced by contracture, they are still capable of generating action potentials in response to electrical field stimulation.
Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48202.
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Anderson
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Dutta
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014812:Vitamin K / Q000494:pharmacology*
D005609:Free Radicals; D014812:Vitamin K; D005978:Glutathione; D002118:Calcium