The MPTP status during early reoxygenation is critical for cardioprotection.

Abstract

BACKGROUND:

Previous studies have revealed that the mitochondrial permeability transition pore (MPTP) plays a critical role in necrotic and apoptotic cell death. Given the opposed roles of the MPTP in cardioprotection (transient versus sustained opening) the primary aim of this study was to determine how two structurally different MPTP inhibitors (cyclosporine A and bongkrekic acid) administered for varying time regimes influenced ischemia/reperfusion (I/R)-induced injury in myocardial slices from rat left ventricle. A second objective was to explore how pharmacologic MPTP opening (using atractyloside) at different time points during I/R modulated myocardial injury.

MATERIALS AND METHODS:

Myocardial slices from rat left ventricle were subjected to 90 min ischemia/120 min reoxygenation at 37°C. MPTP inhibitors and openers were added at various time points during the experimental regime. Tissue injury was assessed by creatine kinase (CK) released and determination of cell necrosis and apoptosis. Myocardial caspase 3 activity was also determined.

RESULTS:

The results show that the status of MPTP can dramatically influence ischemic/reoxygenation induced injury and protection of the rat left ventricular myocardium. Importantly, the status of the MPTP during first 10 min of reoxygenation is of critical importance with both opening and closing of the pore being as protective as ischemic preconditioning.

CONCLUSIONS:

The present study has shown that both formation and inhibition of the MPTP can be exploited for therapeutic purposes and that there is a defined therapeutic window, with the first few minutes of reoxygenation being a crucial period to achieve cardioprotection.

• Authors: Mohammad Ali Husainy, John M Dickenson, Manuel Galiñanes
• Journal: The Journal of surgical research (J Surg Res) Vol. 174 Issue 1 Pg. 62-72 (May 01 2012) ISSN: 1095-8673 [Electronic] United States
• PMID: 21316705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Bongkrekic Acid
• Atractyloside
• Cyclosporine
• Caspase 3
• Oxygen

Topics

• Animals
• Atractyloside (pharmacology)
• Bongkrekic Acid (pharmacology)
• Caspase 3 (metabolism)
• Cyclosporine (pharmacology)
• Male
• Mitochondrial Membrane Transport Proteins (drug effects)
• Mitochondrial Permeability Transition Pore
• Myocardial Reperfusion Injury (prevention & control)
• Oxygen (metabolism)
• Rats
• Rats, Wistar