Pharmacological intervention for prevention of left ventricular remodeling and improving prognosis in myocardial infarction.

Early reperfusion of totally occluded coronary arteries with thrombolysis and/or percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) reduces infarct size, cardiac mortality, and in-hospital events.1,2 Prompt reperfusion of epicardial blood flow reduces infarct size and mortality rates, in-hospital events, and reinfarction. Furthermore, successful reperfusion greatly affects the reduction in infarct size and left ventricular (LV) function. The reduction in infarct size and the improvement in LV ejection fraction may decrease mechanical stress on the noninfarcted myocardium, preventing LV remodeling, including changes in LV size and shape.3 Preventing LV remodeling is of key importance after AMI because it may be related to a reduction in adverse cardiac events, including exacerbation of congestive heart failure and cardiac mortality rates.4–7 Although reperfusion therapy relieves and reduces ischemia and necrosis, the process of restoring coronary blood flow causes ischemiareperfusion injury in the ischemic myocardium, which limits the beneficial effects of reperfusion and may contribute to mortality despite successful reperfusion therapy.8,9 Reperfusion injury is triggered by cellular and mitochondrial calcium overload, oxidant stress, endothelial dysfunction, reduction in nitric oxide production, and other factors. Because reperfusion injury limits the efficacy of reperfusion therapy alone, combined use with pharmacological intervention may moderate microcirculatory impairment and clinical outcomes. Such treatments may eventually reduce infarction size and prevent ischemic LV remodeling after AMI. Furthermore, medication in the chronic phase may affect LV remodeling and clinical prognoses. We undertook a systematic review of the literature based on pharmacological reductions in infarct size and prevention of LV remodeling, both of which may be associated with improved clinical outcomes, in cases of MI. In this review, searches through MEDLINE, LILACS, and SCIELO were the sources of information. Articles were selected by their content related to the theme. The authors had full access to and take responsibility for the integrity of the data. All authors have read and agree to the manuscript as written. Ischemic Preconditioning and Postconditioning in AMI Transient episodes of angina preceding AMI protect the myocardium from ischemic damage. This phenomenon is known as the preconditioning effect. Murry et al10 first reported the ischemic preconditioning phenomenon in an experimental model; it has been supported by numerous experimental cases11,12 and has been found in humans with ischemic heart disease13–19 (Table 1). Some studies showed that brief episodes of ischemia in patients with repetitive balloon inflation during PCI13,14 relieve angina attack and ST elevation in an ECG. In cases of AMI, patients with prodromal angina seem to have reduced infarct size and better prognoses.15–19 In addition, LV remodeling is prevented after the onset of MI.18,19 Thus, preconditioning effects are now used in pharmacological adjuncts to reperfusion therapy. Two forms of ischemic preconditioning are recognized: an early or classic preconditioning, which develops immediately after the ischemic stress and lasts for 1 to 2 hours, and delayed preconditioning or the second window, which reappears 12 to 24 hours later and lasts for 3 to 4 days.20 Although many are still unclear, various mechanisms have been identified through experimentally established signal transduction of such ischemic preconditioning effects. As the cellular pathways to preconditioning, the activation of protein kinase C is triggered by the adenosine A1 and A3 receptors, 5 -nucleotidase activity, and so on.23–27 Beyond the activation of protein kinase C, the mitochondrial and sarcolemmal adenosine triphosphate (ATP)–sensitive K channels play a key role, particularly in early preconditioning.28–32 Mitogenactivated protein kinase families, including p42/p44 mitogenactivated protein kinases, p38 kinase, and the stress-activated c-jun N-terminal kinase, are thought to be important signaling components for both forms of preconditioning.20,33 Nitric oxide induces a late preconditioning against myocardial stunning through a protein kinase C–dependent pathway.34 Early preconditioning is mediated mainly by the opening of the K-ATP channels. In the ischemic myocardium, the sarcolemmal K-ATP channels are activated by intracellular