Curriculum in CardiologyClinical perspectives on reperfusion injury in acute myocardial infarction
Section snippets
Historical perspective
In 1960, Jennings et al 2 induced myocardial necrosis and reperfusion in the canine model and showed histologic features of “explosive” cell swelling along with contracture of myofibrils. Significant disruption of the sarcolemma was noted with an abundant appearance of intramitochondrial calcium phosphate particles. Similar findings were reported in 1977 when Bulkely and Hutchins 3 reported a “paradox of myocardial necrosis” in humans after successful revascularization with coronary artery
No-reflow phenomenon
Described by Kloner et al,5 no reflow occurs when the release of vascular occlusion does not translate toward restoration of coronary blood flow. It refers to the impedance of microvascular blood flow encountered despite patency of the epicardial infarct-related artery. The clinical significance of suboptimal coronary blood flow is of particular importance given its association with poor inhospital major adverse cardiac events (MACE) and 1-year mortality.6 The presence of Thrombolysis In
Reperfusion injury
During reperfusion, the inflammatory cascade facilitates white blood cells to release inflammatory mediators such as interleukins and activating complement leading to myocardial injury.11 Reperfusion is a prothrombotic environment in which platelets become activated resulting in “platelet plugging” of the microvasculature.12 This distal occlusive phenomenon is further exacerbated by atheromatous debris disrupted during the course of mechanical intervention. Reintroduction of oxygen potentiates
Modulators of reperfusion injury
The mediators of lethal reperfusion injury have continued to elude clinicians despite ongoing research efforts to attenuate cardiac myocyte injury. Figure 3 outlines the various pharmacologic therapies tested in clinical trials of which the details are summarized below.
Alternative methods to reduce reperfusion injury
The limited success with prior studies of cardioprotective agents to treat reperfusion injury has engendered continuing exploration of additional therapies. The table provides a brief summary of key clinical studies using new techniques and pharmacology using novel physiologic pathways to provide myocardial protection.
Temporal relationship between reperfusion and cardioprotection
The duration of symptoms before presentation is a key modulator of outcomes with reperfusion. As seen in Figure 4, a temporal relationship also exists with cardioprotection: reperfusion initiated early, during symptom presentation of STEMI, can minimize or even abort myocardial necrosis and reduce the likelihood of reperfusion injury.52 However, between 2 and 6 hours, an abrupt decline of salvaged myocardium occurs, and after 12 hours, recovery of viable myocardium is minimal with reperfusion.53
Summary
Prompt recanalization of the infarct-related artery in STEMI is paramount to improve clinical outcome, but despite enormous advances in trying to accomplish this objective, it is rarely achieved. Moreover, despite the conventional focus on establishing epicardial coronary patency, this metric does not necessarily align with myocardial perfusion. Known as the Achilles heel of reperfusion, research efforts have increasingly focused on strategies to reduce myocardial injury. With the discovery of
Disclosures
No extramural funding was used to support this work. The authors are solely responsible for the design and conduct of this review, the drafting and editing of the manuscript, and its final contents.
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