HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/H2088    most recent 01345.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Pasdois, P. Articles by Santos, P. D. PubMed PubMed Citation Articles by Pasdois, P. Articles by Santos, P. D.

Effect of diazoxide on flavoprotein oxidation and reactive oxygen species generation during ischemia-reperfusion: a study on Langendorff-perfused rat hearts using optic fibers

¹Institut National de la Santé et de la Recherche Médicale U828; ²Université Victor Segalen Bordeaux 2; and ³Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France

Submitted 16 November 2007 ; accepted in final form 12 February 2008

This study analyzed the oxidant generation during ischemia-reperfusion protocols of Langendorff-perfused rat hearts, preconditioned with a mitochondrial ATP-sensitive potassium channel (mitoK_ATP) opener (i.e., diazoxide). The autofluorescence of mitochondrial flavoproteins, and that of the total NAD(P)H pool on the one hand and the fluorescence of dyes sensitive to H₂O₂ or O₂^– [i.e., the dihydrodichlorofluoroscein (H₂DCF) and dihydroethidine (DHE), respectively] on the other, were noninvasively measured at the surface of the left ventricular wall by means of optic fibers. Isolated perfused rat hearts were subjected to an ischemia-reperfusion protocol. Opening mitoK_ATP with diazoxide (100 µM) 1) improved the recovery of the rate-pressure product after reperfusion (72 ± 2 vs. 16.8 ± 2.5% of baseline value in control group, P < 0.01), and 2) attenuated the oxidant generation during both ischemic (–46 ± 5% H₂DCF oxidation and –40 ± 3% DHE oxidation vs. control group, P < 0.01) and reperfusion (–26 ± 2% H₂DCF oxidation and –23 ± 2% DHE oxidation vs. control group, P < 0.01) periods. All of these effects were abolished by coperfusion of 5-hydroxydecanoic acid (500 µM), a mitoK_ATP blocker. During the preconditioning phase, diazoxide induced a transient, reversible, and 5-hydroxydecanoic acid-sensitive flavoprotein and H₂DCF (but not DHE) oxidation. In conclusion, the diazoxide-mediated cardioprotection is supported by a moderate H₂O₂ production during the preconditioning phase and a strong decrease in oxidant generation during the subsequent ischemic and reperfusion phases.

cardioprotection; 5-hydroxydecanoate