Mechanism of Ischemia and Reperfusion Injury to the Heart: From the Viewpoint of Nitric Oxide and Mitochondria

Abstract

After an acute myocardial infarction, early and successful myocardial reperfusion is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome. However, the process of restoring blood flow to the ischemic myocardium can induce injury. This phenomenon,termed myocardial reperfusion injury, can paradoxically reduce the beneficial effects of myocardial reperfusion and lead to lethal damage to myocardium. During cardiac ischemia-reperfusion (IR) injury, excessive generation of reactive oxygen species (ROS), overload of intracellular Ca 2+ , H + leakage at the mitochondrial level, inflammation, and metabolic modulations lead to opening of the mitochondrial permeability transition pore(PTP) on reperfusion. This can result in the depletion of ATP, irreversible oxidation of proteins, lipids, and DNA within the cardiomyocyte, and can trigger apoptosis. In contrast, mitochondria also plays an important role in the cardioprotective signaling processes of ischemic preconditioning (IPC), to prevent IR injury. Nitric oxide (NO) generated constitutively within the heart has long been known to influence myocardial function. But, Nitric oxide (NO) has emerged as a potent effector molecule for a variety of cardioprotective strategies, including IPC. Whereas NO is most noted for its activation of the "classic" soluble guanylate cyclase (sGC) signaling pathway, emerging evidence indicates that NO can directly act on mitochondria, independent of the sGC pathway, affording acute cardioprotection against IR injury. These effects of NO on mitochondria and mitochondrial role during IR injury are the focus of this review.

Quantitative and qualitative analysis of heart mitochondria for evaluating the degree of myocardial injury utilizing atomic force microscopy

“…When the myocardium is not reperfused, it becomes entirely subject to ischemic cell death (Garcia-Dorado and Piper, 2006). Although reperfusion disturbs the process of ischemic cell death, it imposes injury in an early stage that results in further cell death (Ha and Kim, 2010). It is well known that reperfusion injury is mainly induced by reactive oxygen species (De Celle et al, 2004;Flaherty and Weisfeldt, 1988).…”

Roles of mitochondrial dynamics modulators in cardiac ischaemia/reperfusion injury

“…Currently, an imbalance between mitochondrial fission and fusion has been shown to contribute to many cardiac pathologies including myocardial I/R injury . Mitochondria are crucial to the control of cell survival, especially in the heart, and they require mitochondrial dynamics, which generate ATP substrates to power cell activity .…”

Intravenous (−)-epicatechin reduces myocardial ischemic injury by protecting mitochondrial function

“…With ischemia, the loss of O 2 and consequent decrease in ATP levels disrupts cardiac myocyte ionic homeostasis resulting in depolarization and cytoplasmic Ca 2+ accumulation [15]. Upon reperfusion and re-establishment of the mitochondrial membrane potential, excess Ca 2+ enters the mitochondria and can trigger cardiac myocyte death by multiple mechanisms, including oxidative injury and opening of the mitochondrial permeability transition pore (MPTP) [2,16–18]. Of interest is that stabilizing mitochondrial structure/function during IR preserves myocyte viability and can lead to improved clinical outcomes [15].…”