Mitochondrial Involvement in Cardiac Apoptosis During Ischemia and Reperfusion: Can We Close the Box?

Abstract

Myocardial ischemia is the main cause of death in the Western societies. Therapeutic strategies aimed to protect the ischemic myocardium have been extensively studied. Reperfusion is the definitive treatment for acute coronary syndromes, especially acute myocardial infarction; however, reperfusion has the potential to exacerbate tissue injury, a process termed reperfusion injury. Ischemia/reperfusion (I/R) injury may lead to cardiac arrhythmias and contractile dysfunction that involve apoptosis and necrosis in the heart. The present review describes the mitochondrial role on cardiomyocyte death and some potential pharmacological strategies aimed at preventing the opening of the box, i.e., mitochondrial dysfunction and membrane permeabilization that result into cell death. Data in the literature suggest that mitochondrial disruption during I/R can be avoided, although uncertainties still exist, including the fact that the optimal windows of treatment are still fairly unknown. Despite this, the protection of cardiac mitochondrial function should be critical for the patient survival, and new strategies to avoid mitochondrial alterations should be designed to avoid cardiomyocyte loss.

Remote pharmacological preconditioning on median nerve territory increases Hsp32 expression and attenuates ischemia–reperfusion injury in rat heart

“…Their protocols focus on assessment of the infarct size and the area-at-risk by Evan's blue dye and triphenyl tetrazolium chloride following 4-h period of reperfusion, indicating that 4-h reperfusion is necessary to observe a prominent change of infarction size. Although morphological variable such as infarction size is generally used to evaluate myocardial I/R injury, recent studies suggest functional variables such as reperfusion ventricular arrhythmias and contractile performance provide important information as well (Machado et al, 2009;Meyer et al, 2010;Xiao et al, 2010). It would have been more appropriate to assess the actual infarct size, but our results showed that there was no significant difference, in terms of infarction size, between different groups (data not shown).…”

A novel cardioprotective p38-MAPK/mTOR pathway

“…Reperfusion is the definitive treatment for acute coronary syndromes including myocardial infarction (MI), but reperfusion injury is, at this point, largely unavoidable [1]. Reactive oxygen species (ROS), which activate a host of signaling pathways including, among others, the stress-activated protein kinases, are key mediators of I/R injury.…”

Pim-1 preserves mitochondrial morphology by inhibiting dynamin-related protein 1 translocation

“…Many simultaneous cellular changes occur during cardiac ischemia and inevitably cause cell death. Mitochondria are especially sensitive to ischemic insult and trigger the initiation of apoptotic signaling (1). Recently, mitochondrial morphological dynamics have been reported to play a role in ischemia/reperfusion injury (2,3).…”