Ischemia cellular mechanisms

Piper H.M., Meuter K., Schafer C. Cellular mechanisms of ischemia-reperfusion injury. Ann. Thorac. Surg. 75 (2003) S644-S648. 

Fig. 4.7 Schematic representation of the myriad reperfusion-induced processes. Many of the events listed may be the consequence of ischemia-induced changes and yet others may be in response to the reintroduction of oxygen and glucose to an ischemic milieu in which many of the cellular mechanisms may have been severely perturbed...

EPC is the endogenous cellular protective mechanism in the heart by which brief periods of ischemia induce protection against infarction due to subsequent longer periods of ischemia. 

Despite the extensive research efforts during the last 15 years, the relative contribution of apoptosis and necrosis to cell loss in heart disease remains controversial. The type of cell death in the heart often depends on the time in the natural history when it is studied necrosis is a feature of early heart failure, especially if caused by ischemia, but the cause of cell death in chronic heart failure is mainly apoptotic or autophagic [19-21], Moreover, it is possible that apoptotic and necrotic cell deaths represent two ends of continuum of response to an injury [22] cells may initially begin to die from apoptotic mechanism, but as cellular energy declines, the cells continue to die of necrosis [23],... 

The concept of neuroprotection relies on the fact that delayed neuronal injury occurs after ischemia, and each step along the ischemic cascade provides a target for therapeutic intervention. Thus, understanding the cellular and molecular mechanisms that underlie the development of neuronal and vascular injury is critical to optimize treatment. This chapter reviews experimental evidence from studies on focal cerebral ischemia and mild hypothermia, as well as the mechanisms involved in mild hypothermic neuroprotection. 

Although the major thrust of this chapter is centered on the free radical hypothesis of myocardial injury, it is essential to realize that calcium overload in myocardial cells during ischemia and reperfusion could be the primary cause of myocardial injury [40,41]. It is also likely that mechanisms of free radical production and calcium overload are related and not mutually exclusive [40]. Alterations in intracellular calcium homeostasis are often accompanied by depletion of cellular antioxidants [42]. The mitochondrial Ca2+ homeostasis has been shown to affect oxy radicals produced through the electron-transport chain [43], Reperfusion and reoxygenation of hearts are characterized by marked increase in cytosolic and mitochondrial levels of Ca2+ [44]. Ruthenium red, which inhibits mitochondrial Ca2+ uptake, also protects the heart against reperfusion-induced damage [45,46],... 

The Na /K ATPase is the main active transport mechanism responsible for maintaining ionic homeostasis, and this process involves continuous expenditure of ATP. Normal cell volume depends on the constant extrusion of intracellular Na by the Na /K ATPase. Ischemia/hypoxia results in abrogation of mitochondrial oxidative phosphorylation, and a rapid loss of ATP compromising the cellular ionic homeostasis. Sodium ion influx drives Cl influx via chloride channels, resulting in an increased osmolarity inside the cell that drives inflow of water mainly via AQP channels (Badaut et al., 2002 Amiry-Moghaddam and Ottersen, 2003 Liang et al.,... 

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