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01-11-2011 | Original Contribution

The role of mitochondrial permeability transition in reperfusion-induced cardiomyocyte death depends on the duration of ischemia

Authors: Marisol Ruiz-Meana, Javier Inserte, Celia Fernandez-Sanz, Victor Hernando, Elisabet Miro-Casas, Ignasi Barba, David Garcia-Dorado

Published in: Basic Research in Cardiology | Issue 6/2011

Abstract

Mitochondrial permeability transition (MPT) is critical in cardiomyocyte death during reperfusion but it is not the only mechanism responsible for cell injury. The objectives of the study is to investigate the role of the duration of myocardial ischemia on mitochondrial integrity and cardiomyocyte death. Mitochondrial membrane potential (ΔΨm, JC-1) and MPT (calcein) were studied in cardiomyocytes from wild-type and cyclophilin D (CyD) KO mice refractory to MPT, submitted to simulated ischemia and 10 min reperfusion. Reperfusion after 15 min simulated ischemia induced a rapid recovery of ΔΨm, extreme cell shortening (contracture) and mitochondrial calcein release, and CyD ablation did not affect these changes or cell death. However, when reperfusion was performed after 25 min simulated ischemia, CyD ablation improved ΔΨm recovery and reduced calcein release and cell death (57.8 ± 4.9% vs. 77.3 ± 4.8%, P < 0.01). In a Langendorff system, CyD ablation increased infarct size after 30 min of ischemia (61.3 ± 6.4% vs. 45.3 ± 4.0%, P = 0.02) but reduced it when ischemia was prolonged to 60 min (52.8 ± 8.1% vs. 87.6 ± 3.7%, P < 0.01). NMR spectroscopy in rat hearts showed a rapid recovery of phosphocreatine after 30 min ischemia followed by a marked decay associated with contracture and LDH release, that were preventable with contractile blockade but not with cyclosporine A. In contrast, after 50 min ischemia, phosphocreatine recovery was impaired even with contractile blockade (65.2 ± 4% at 2 min), and cyclosporine A reduced contracture, LDH release and infarct size (52.1 ± 4.2% vs. 82.8 ± 3.6%, P < 0.01). In conclusion, the duration of ischemia critically determines the importance of MPT on reperfusion injury. Mechanisms other than MPT may play an important role in cell death after less severe ischemia.

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Title: The role of mitochondrial permeability transition in reperfusion-induced cardiomyocyte death depends on the duration of ischemia
Authors: Marisol Ruiz-Meana
Javier Inserte
Celia Fernandez-Sanz
Victor Hernando
Elisabet Miro-Casas
Ignasi Barba
David Garcia-Dorado
Publication date: 01-11-2011
Publisher: Springer-Verlag
Published in: Basic Research in Cardiology / Issue 6/2011
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-011-0225-5

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The role of mitochondrial permeability transition in reperfusion-induced cardiomyocyte death depends on the duration of ischemia

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