Cardioprotection and pharmacological therapies in acute myocardial infarction: Challenges in the current era

Abstract

In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, preserving left-ventricular systolic function and reducing the onset of heart failure. Within minutes after the restoration of blood flow, however, reperfusion itself results in additional damage, also known as myocardial ischemia-reperfusion injury. An improved understanding of the pathophysiological mechanisms underlying reperfusion injury has resulted in the identification of several promising pharmacological (cyclosporin-A, exenatide, glucose-insulin-potassium, atrial natriuretic peptide, adenosine, abciximab, erythropoietin, metoprolol and melatonin) therapeutic strategies for reducing the severity of myocardial reperfusion injury. Many of these agents have shown promise in initial proof-of-principle clinical studies. In this article, we review the pathophysiology underlying myocardial reperfusion injury and highlight the potential pharmacological interventions which could be used in the future to prevent reperfusion injury and improve clinical outcomes in patients with coronary heart disease.

Keywords: Adjunctive therapy; Cardioprotection; Infarct size; Myocardial reperfusion injury; ST-elevation myocardial infarction.

Figure 1

Scheme of mechanism of myocardial injury by a reperfusion process. MPTP: Mitochondrial permeability transition pore; ROS: Reactive oxygen species; RAS: Renin-Angiotensin system; NPS: Neutrophil-Platelet system; CS: Complement system; MI: Myocardial infarction; MACE: Major adverse cardiac events.