Diazoxide, a KATP Channel Opener, Prevents Ischemia–Reperfusion Injury in Rodent Pancreatic Islets

Hydrogen sulfide has been shown to protect myocardium against ischemia-reperfusion injury by preserving interfibrillar mitochondria functional activi-ties than subsarcolemmal mitochondria. In this study, the role of the KATP channel in modulating the mitochondrial subpopulations during the cardioprotection mediated by NaSH (H2S donor) was investigated. Isolated rat hearts were treated with mitochondrial KATP channel closer glibenclamide (10 μM)/opener diazoxide (0.8 mM) via Langendorff perfusion apparatus before ischemia-reperfusion. The results showed that NaSH pre-conditioning in presence of glibenclamide significantly improved cardiac recovery without any significant difference between interfibrillar mitochondria and subsarcolemmal mitochondria. In conclusion, targeting KATP channel may not be good option to target interfibrillar mitochondria/subsarcolemmal mitochondria against ischemia-reperfusion injury.

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Decreased DNA Damage and Increased DNA Repair by Mitochondrial Membrane K-ATP Channel Opener in Rabbit Spinal Cords Following Ischemia-Reperfusion Injury

Microscopy and Microanalysis ◽

10.1017/s1431927604883739 ◽

2004 ◽

Vol 10 (S02) ◽

pp. 1412-1413

Author(s):

S H Mcklaren ◽

Daqing Gao ◽

Lei Chen ◽

Glen Roseborough ◽

G M Williams ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Reperfusion Injury ◽

Mitochondrial Membrane ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Channel Opener

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.

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Noninvasive Delayed Limb Ischemic Preconditioning Attenuates Myocardial Ischemia-Reperfusion Injury in Rats by a Mitochondrial KATP Channel-Dependent Mechanism

Physiological Research ◽

10.33549/physiolres.931944 ◽

2011 ◽

pp. 271-279 ◽

Cited By ~ 16

Author(s):

Y.-N. WU ◽

H. YU ◽

X.-H. ZHU ◽

H.-J. YUAN ◽

Y. KANG ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Ischemic Preconditioning ◽

Katp Channel ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Control Group ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion ◽

Dependent Mechanism

We previously demonstrated in rats that noninvasive delayed limb ischemic preconditioning (LIPC) induced by three cycles of 5-min occlusion and 5-min reperfusion of the left hind limb per day for three days confers the same cardioprotective effect as local ischemic preconditioning of the heart, but the mechanism has not been studied in depth. The aim of this project was to test the hypothesis that delayed LIPC enhances myocardial antioxidative ability during ischemia-reperfusion by a mitochondrial KATP channel (mito KATP)-dependent mechanism. Rats were randomized to five groups: ischemia-reperfusion (IR)-control group, myocardial ischemic preconditioning (MIPC) group, LIPC group, IR-5HD group and LIPC-5HD group. The MIPC group underwent local ischemic preconditioning induced by three cycles of 5-min occlusion and 5-min reperfusion of the left anterior descending coronary arteries. The LIPC and LIPC-5HD groups underwent LIPC induced by three cycles of 5-min occlusion and 5-min reperfusion of the left hind limb using a modified blood pressure aerocyst per day for three days. All rats were subjected to myocardial ischemia-reperfusion injury. The IR-5HD and LIPC-5HD groups received the mito KATP channel blocker 5-hydroxydecanoate Na (5-HD) before and during the myocardial ischemia-reperfusion injury. Compared with the IR-control group, both the LIPC and MIPC groups showed an amelioration of ventricular arrhythmia, reduced myocardial infarct size, increased activities of total superoxide dismutase, manganese-superoxide dismutase (Mn-SOD) and glutathione peroxidase, increased expression of Mn-SOD mRNA and decreased xanthine oxidase activity and malondialdehyde concentration. These beneficial effects of LIPC were prevented by 5-HD. In conclusion, delayed LIPC offers similar cardioprotection as local IPC. These results support the hypothesis that the activation of mito KATP channels enhances myocardial antioxidative ability during ischemia-reperfusion, thereby contributing, at least in part, to the anti-arrhythmic and anti-infarct effects of delayed LIPC.

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