Delayed low pressure at reperfusion: A new approach for cardioprotection.

René Ferrera, Souhila Benhabbouche, Claire Crola Da Silva, Muhammad Rizwan Alam, Michel Ovize

Index: J. Thorac. Cardiovasc. Surg. 150 , 1641-1648.e2, (2015)

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Abstract

The aims of this study were to evaluate whether the delayed application of low-pressure reperfusion could reduce lethal reperfusion injury and whether the inhibition of the opening of the mitochondrial permeability transition pore is involved in this protection.Isolated rat hearts (n = 120) underwent 40 minutes of global ischemia followed by 60 minutes of reperfusion. Hearts were randomly assigned to the following groups: control, postconditioning (comprising 2 episodes of 30 seconds of ischemia and 30 seconds of reperfusion), and low-pressure reperfusion (using a reduction of perfusion pressure at 70 cm H2O for 10 minutes). In additional groups, postconditioning and low-pressure reperfusion were applied after a delay of 3, 10, and 20 minutes after the initial 40-minute ischemic insult.As expected, infarct size (triphenyltetrazolium chloride staining) and lactate dehydrogenase release were significantly reduced in low-pressure reperfusion and postconditioning versus controls (P < .01), whereas functional parameters (coronary flow, rate pressure product) were improved (P < .01). Although delaying postconditioning by more than 3 minutes resulted in a loss of protection, low-pressure reperfusion still significantly reduced infarct size when applied as late as 20 minutes after reperfusion. This delayed low-pressure reperfusion protection was associated with an improved mitochondrial respiration, lower reactive oxygen species production, and enhanced calcium retention capacity, related to inhibition of permeability transition pore opening.We demonstrated for the first time that low-pressure reperfusion can reduce lethal myocardial reperfusion injury even when performed 10 to 20 minutes after the initiation of reperfusion.Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.