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Cardioprotection by multiple preconditioning cycles does not require mitochondrial K(ATP) channels in pigs
Lisa M Schwartz1, Timothy S Welch, Mark S Crago
1Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA. lschwartz@usuhs.mil
American Journal of Physiology. Heart and Circulatory Physiology
|September 18, 2002
Summary
Ischemic preconditioning protects the heart, but opening mitochondrial K(ATP) channels isn't required for this endogenous effect. Pharmacological preconditioning via diazoxide, however, does rely on these channels for its cardioprotective benefits.
Area of Science:
- Cardiovascular Physiology
- Mitochondrial Biology
- Pharmacology
Background:
- Ischemic preconditioning (IP) confers significant cardioprotection against ischemia-reperfusion injury.
- Mitochondrial ATP-sensitive potassium (K(ATP)) channels are implicated in various cardioprotective pathways.
- The precise role of mitochondrial K(ATP) channels in endogenous IP remains debated.
Purpose of the Study:
- To investigate whether the cardioprotection induced by ischemic preconditioning in pigs is dependent on the opening of mitochondrial K(ATP) channels.
- To compare the effect of blocking mitochondrial K(ATP) channels on endogenous IP versus pharmacologically induced cardioprotection.
Main Methods:
- Open-chest pigs underwent 30 minutes of left anterior descending coronary artery occlusion followed by 3 hours of reflow.
- Ischemic preconditioning was induced using two cycles of 5-minute occlusion and 10-minute reperfusion.
- Mitochondrial K(ATP) channel blockade was achieved using 5-hydroxydecanoate (5-HD).
- Pharmacological preconditioning was induced using diazoxide.
Main Results:
- Ischemic preconditioning significantly reduced infarct size (2.7% vs. 35.1% in control).
- 5-Hydroxydecanoate did not abolish the infarct-limiting effect of ischemic preconditioning.
- Diazoxide significantly reduced infarct size, and this effect was abolished by 5-hydroxydecanoate.
- These findings indicate that mitochondrial K(ATP) channel opening is cardioprotective but not essential for endogenous ischemic preconditioning.
Conclusions:
- Mitochondrial K(ATP) channel opening is a confirmed mechanism of cardioprotection in pigs.
- Endogenous cardioprotection from ischemic preconditioning does not require the opening of mitochondrial K(ATP) channels.
- Pharmacological preconditioning with diazoxide relies on mitochondrial K(ATP) channel activation for its protective effects.