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Ischemic preconditioning prevents reperfusion heart injury in cardiac hypertrophy by activation of mitochondrial KATP channels.

Abstract：

BACKGROUND:Cardiac hypertrophy has been demonstrated to decreases the ATP-sensitive potassium channels (K(ATP)), the major protective mechanism following the energy depletion, a common condition seen during the reperfusion after open heart surgery. In this study we have demonstrated the role of ischemic preconditioning (IP) in preventing the reperfusion injury of the hypertrophied heart by activation of the depleted K(ATP) channels. METHODS:Pressure overload left ventricular hypertrophy was induced in 6 weeks old male Wistar rats by supra renal transverse abdominal aortic constriction and the study was conducted 10-12 weeks later. Hypertrophied rats were subjected to IP protocols by four episodes of 3 min ischemia each being separated by 10 min reperfusion, followed by 30 min of sustained ischemia and 120 min of reperfusion with or without treating the rats with K(ATP) channel antagonists 5-hydroxydecanoic acid (10 mg/kg per i.v.) or glibenclamide (1 mg/kg per i.v.), 10 min before the sustained ischemia. RESULTS:IP resulted in (a) less incidence of ventricular arrhythmias (b) less area of myocardial infarction (9.3% vs. 48.1%, IP to control) (c) less tissue water content (76.5% vs. 94.8%, IP to control) (d) well preserved myocardial ATP content (P<0.001 from control) content and (e) much fewer apoptotic cells (4.7% vs. 13.2%, IP to control). Pre treating the rats with the K(ATP) channel inhibitors before sustained ischemia resulted in inhibition of these protective effects of IP on cardiac hypertrophy. CONCLUSION:The above results, therefore, suggest to us that IP by activation of K(ATP) channels can afford protection against the ischemia-reperfusion injury in the hypertrophied heart.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Rajesh KG,Sasaguri S,Suzuki R,Xing Y,Maeda H

doi

10.1016/j.ijcard.2003.06.010

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

41-9

issue

1

eissn

0167-5273

issn

1874-1754

pii

S0167527303004480

journal_volume

96

pub_type

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