Ischemic preconditioning - From the first to the second window of protection

In many species one or more brief coronary occlusions limit the injuries wh ich a subsequent ischemia-reperfusion can produce in the myocardium. A simi lar protection has been observed in the majority of organ systems. A first period or window of protection can lasts up to 3 hours and is followed by a second window of protection (SWOP) which begins about 24 hours after the b rief coronary occlusions and lasts about 72 hours. Increase of the release of endogenous agents such as adenosine and nitric oxide (NO) may be respons ible for both windows through the activation of a protein-kinase C (PKC) wh ich in turn activates ATP sensitive potassium (Kf,,) channels. Nitric oxide is also reported to act directly on K+ (ATP) channels. Recently, it has be en suggested that the channels involved in the protection are mitochondrial rather than sarcolemmal. In SWOP the origin of NO is attributed to the act ivity of an inducible NO-synthase. Free oxygen radicals released during pre conditioning are likely to take part in the delayed protection through the production of peroxynitrite which activates PKC and through the increase of the activity of antioxidant enzymes such as Mn superoxide-dismutase. The p roduction of heat shock proteins is considered a marker rather than a mecha nism of SWOP. (C) 2001 Elsevier Science Inc. All rights reserved.