In vivo hyperoxic preconditioning protects against rat-heart ischemia/reperfusion injury by inhibiting mitochondrial permeability transition pore opening and cytochrome c release.

Abstract

In vivo hyperoxic preconditioning (PC) has been shown to protect against ischemia/reperfusion (I/R) myocardial damage. Mitochondrial permeability transition pore (MPTP) opening is an important event in cardiomyocyte cell death occurring during I/R and therefore a possible target for cardioprotection. We tested the hypothesis that in vivo hyperoxic PC, obtained by mechanical ventilation of animals, could protect heart against I/R injury by inhibiting MPTP opening and cytochrome c release from mitochondria. Mechanically ventilated rats were first exposed to a short period of hyperoxia and isolated hearts were subsequently subjected to I/R in a Langendorff apparatus. Hyperoxic PC significantly improved the functional recovery of hearts on reperfusion, reduced the infarct size, and decreased necrotic damage as shown by the reduced release of lactate dehydrogenase. Mitochondria from hyperoxic PC hearts were less sensitive than mitochondria from reperfused heart to MPTP opening. In addition, hyperoxic PC prevented mitochondrial NAD(+) depletion, an indicator of MPTP opening, and cytochrome c release as well as cardiolipin oxidation/depletion associated with I/R. Together, these results demonstrate that hyperoxic PC protects against heart I/R injury by inhibiting MPTP opening and cytochrome c release. Thus, in vivo hyperoxic PC may represent a useful strategy for the treatment of cardiac I/R injury and could have potential applications in clinical practice.

• Authors: G Petrosillo, N Di Venosa, N Moro, G Colantuono, V Paradies, E Tiravanti, A Federici, F M Ruggiero, G Paradies
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 50 Issue 3 Pg. 477-83 (Feb 01 2011) ISSN: 1873-4596 [Electronic] United States
• PMID: 21130864 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Cardiolipins
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• NAD
• Cytochromes c
• Oxygen
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Cardiolipins (metabolism)
• Cytochromes c (metabolism)
• Hyperoxia
• Male
• Mitochondrial Membrane Transport Proteins (metabolism)
• Mitochondrial Membranes (metabolism)
• Mitochondrial Permeability Transition Pore
• Myocardial Infarction (metabolism, pathology, prevention & control)
• Myocardial Reperfusion Injury (metabolism, pathology, prevention & control)
• Myocardium (metabolism, pathology)
• NAD (metabolism)
• Necrosis
• Oxygen (pharmacology)
• Rats
• Rats, Wistar