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Pasdois 2008 Am J Physiol Heart Circ Physiol

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Pasdois P, Beauvoit B, Tariosse L, Vinassa B, Bonoron-Adèle S, Dos Santos P (2008) Effect of diazoxide on flavoprotein oxidation and reactive oxygen species generation during ischemia-reperfusion: a study on Langendorff-perfused rat hearts using optic fibers. Am J Physiol Heart Circ Physiol 294:H2088-97.

» PMID: 18296562 Open Access

Pasdois P, Beauvoit B, Tariosse L, Vinassa B, Bonoron-Adèle S, Dos Santos P (2008) Am J Physiol Heart Circ Physiol

Abstract: 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 H(2)O(2) or O(2)(*-) [i.e., the dihydrodichlorofluoroscein (H(2)DCF) 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 microM) 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% H(2)DCF oxidation and -40 +/- 3% DHE oxidation vs. control group, P < 0.01) and reperfusion (-26 +/- 2% H(2)DCF 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 microM), a mitoK(ATP) blocker. During the preconditioning phase, diazoxide induced a transient, reversible, and 5-hydroxydecanoic acid-sensitive flavoprotein and H(2)DCF (but not DHE) oxidation. In conclusion, the diazoxide-mediated cardioprotection is supported by a moderate H(2)O(2) production during the preconditioning phase and a strong decrease in oxidant generation during the subsequent ischemic and reperfusion phases.

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Labels: MiParea: Respiration 

Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Heart 



HRR: Oxygraph-2k 

2020-12