DOI: 10.1097/MCA.0b013e328350a9b8

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PMID: 22274396

Issn Print: 0954-6928

Publication Date: 2012/03/01


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Ignoratio elenchi: myocardial conditioning and reperfusion ‘injury’

Burton E. Sobel; A.K.M. Tarikuz Zaman

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We have recently commented on a conundrum pertaining to so-called reperfusion injury 1. In essence, we indicated that it is ineluctably clear that reperfusion induced by early coronary revascularization is the lynch pin of modern therapy for treatment of acute coronary syndromes (reviewed by Gogo et al.2). How then can it also be blamed for inducing incremental injury, that is, injury beyond that which would have occurred in association with persistent ischemia without reperfusion? One could argue that reperfusion exerts two opposing types of effects. The first might be favorable effects such as salvaging jeopardized myocardium or decreasing the size of the risk region. The second might be unfavorable effects like incremental reperfusion injury. If so, the former must outweigh the latter. However, this argument seems to be tortuous. We preferred an alternative one that was more consistent with Occam’s razor.
Although manifestations of reperfusion include structural and biochemical changes that occur in reperfused zones but not in persistently ischemic zones, such manifestations do not necessarily reflect incremental injury. Instead, they may simply reflect different manifestations of an ischemic insult when it is associated with reperfusion.
The notion that incremental reperfusion injury exists has been supported by observations of protective effects of conditioning of myocardium on hearts rendered ischemic (reviewed by Opie and Lecour 3). This logic may, however, be an example of one of Aristotle’s 13 fallacies enumerated in his Sophistici Elenchi, that is, the fallacy of ignoratio elenchi or ignorance of refutation. It comprises ‘missing the point’ or alternatively presenting evidence that answers a question other than the one actually being posed. The facts that preconditioning, postconditioning, and remote conditioning can affect the evolution of sequelae of reperfusion and that preconditioning and postconditioning can protect hearts subjected to ischemia do not imply that the two consequences are related. They simply imply that conditioning can protect a myocardium subjected to an ischemic insult and that such conditioning can also attenuate the manifestations of a component of injury seen with reperfusion in the absence of the conditioning. If, in fact, such tissue is blighted already, despite the absence of signs of reperfusion ‘injury’, and if it is doomed to die despite reperfusion, the presence or absence of signs of reperfusion ‘injury’ would not be informative regarding the existence of incremental reperfusion injury.
Brief episodes of myocardial ischemia and reperfusion increase the resistance of the myocardium to a subsequent, longer ischemic insult. This phenomenon, called ischemic preconditioning, was first described by Murry et al. 4 in the Jennings group in 1986. They observed constraint of infarct size in open-chest dogs following four episodes of 5 min of ischemia and 5 min of reperfusion followed by persistent coronary occlusion for 40 min. The hearts were harvested 4 days later. The phenomenon has been observed in diverse animal species. Preconditioning can preserve endothelial cell function reflected by vasorelaxation in response to increasing concentrations of acetylcholine 5. It can decrease accumulation of polymorphonuclear neutrophils detected immunohistochemically in zones of infarction. It can reduce cell death, manifested histologically by a decreased number of terminal transferase UTP nick end labeling positive cells and down regulation of expression of the proapoptotic Bax protein 6. However, it is not necessarily the case that the mechanism underlying the benefits conferred reflect obviation of incremental reperfusion injury. Instead, it may be a result of protection of the ischemic myocardium and a change in the manifestations of injury in zones subjected to reperfusion without salvage of blighted tissue in these regions.
Protection by preconditioning does seem to be inducible in the human heart.

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