Free radicals in myocardial injury

This concept has enormous implications in the setting of cardiac surgery and heart transplantation [11-13]. Conditions of ischemia and reperfusion are created routinely by the surgeon during open heart procedures, i.e., cardiopulmonary bypass and aortic cross-clamping [11,12], Similar conditions prevail during heart transplantation when the ischemic donor heart is rapidly reoxygenated by the recipient s blood [14]. 

Cellular sources of oxy radical and isolated heart models 

Reactive oxygen species can originate from intracellular sources, such as mitochondria and xanthine oxidase, or from extracellular sources such as neutrophils and macrophages [33-35]. Recently, it has been proposed that myoglobin, present in the myocytes, is a potential source of higher oxidants in reperfusion injury [36]. 

The rabbit heart contains only trace amounts of the enzyme xanthine oxidase (as does the human heart) [37,38]. Therefore, this enzyme probably does 

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], 

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