Ischemic preconditioning: from the first to the second window of protection.
In many species one or more brief coronary occlusions limit the injuries which a subsequent ischemia-reperfusion can produce in the myocardium. A similar 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 brief coronary occlusions and lasts about 72 hours. Increase of the release of endogenous agents such as adenosine and nitric oxide (NO) may be responsible for both windows through the activation of a protein-kinase C (PKC) which in turn activates ATP sensitive potassium (K+(ATP)) channels. Nitric oxide is also reported to act directly on K+(ATP) channels. Recently, it has been suggested that the channels involved in the protection are mitochondrial rather than sarcolemmal. In SWOP the origin of NO is attributed to the activity of an inducible NO-synthase. Free oxygen radicals released during preconditioning 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 production of heat shock proteins is considered a marker rather than a mechanism of SWOP.
Pagliaro
P
P
Dipartimento di Scienze Cliniche e Biologiche dell'Università di Torino, Orbassano, Italy.
Gattullo
D
D
Rastaldo
R
R
Losano
G
G
D000241:Adenosine / Q000502:physiology; D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology* / Q000628:therapy*; D005609:Free Radicals; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000378:metabolism; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D015221:Potassium Channels / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism
D005609:Free Radicals; D006360:Heat-Shock Proteins; D015221:Potassium Channels; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D011493:Protein Kinase C; D000241:Adenosine