Post-conditioning Protects From Cardioplegia and Cold Ischemia via Inhibition of Mitochondrial Permeability Transition Pore

René Ferrera, Jean Chrisostome Bopassa, Denis Angoulvant, Michel Ovize

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17 Scopus citations

Abstract

Background: The aim of this study was to evaluate the role of the mitochondrial permeability transition pore (MPTP) in the protection achieved by post-conditioning of hearts submitted to hypothermic cardioplegia and ischemia. Methods: Isolated rat hearts (n = 30) underwent cold cardioplegia (4°C, Celsior solution) and 8 hours of ischemia at 4°C, followed by a 60-minute Langendorff reperfusion. Hearts were randomly assigned to one of two groups: post-conditioning (post-C, consisting of episodes of 30-second ischemia and 30-second reperfusion at onset of reperfusion) or control (no intervention). A sham group was added for which hearts were harvested and immediately reperfused without ischemia. Coronary flow, heart rate, dP/dt and rate-pressure product were measured. Infarct size was assessed by triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and troponin I release analysis. After reperfusion, heart mitochondria were isolated and calcium overload necessary to induce MPTP opening was measured. From the onset of reperfusion, all functional parameters were significantly improved in post-C vs control hearts. Results: Infarct size, measured both by TTC staining and LDH, and CPK and troponin I leakage were lower in post-C hearts (p < 0.01). Mean calcium load needed to induce MPTP opening was higher in post-C mitochondria vs controls (p < 0.01). Conclusions: Post-conditioning protects the rat heart against cold ischemia-reperfusion injury. Our data suggest that this protection involves inhibition of MPTP opening.

Original languageEnglish (US)
Pages (from-to)604-609
Number of pages6
JournalJournal of Heart and Lung Transplantation
Volume26
Issue number6
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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