Ischemic preconditioning against infarction: its mechanism and clinical implications.
Exposing the myocardium to brief ischemia followed by reperfusion enhances myocardial resistance to infarction from a subsequent sustained ischemia. This phenomenon, termed preconditioning, is most likely to be triggered by adenosine A1 receptor activation, and the dependence of the preconditioning effect on the duration of preconditioning ischemia and the number of its repetition is probably through the interstitial adenosine level achieved by each preconditioning protocol. Our studies support the theory that activation of protein kinase C subsequent to stimulation of the A1 receptor enhances myocardial ischemic tolerance. The ATP-sensitive potassium channel may be involved in preconditioning, but its relation with protein kinase C is unclear, and the relative importance of this channel might be species dependent. The mechanism of preconditioning needs to be further elucidated in animal models and preconditioning in the human heart needs to be further characterized before we can adapt its biochemical basis to clinical therapy.
Miura
T
T
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Miki
T
T
Tsuchihashi
K
K
Iimura
O
O
D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000787:Angina Pectoris / Q000150:complications; D000818:Animals; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000517:prevention & control; D017682:Myocardial Stunning; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000378:metabolism
D015221:Potassium Channels; D018047:Receptors, Purinergic P1; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D015720:5'-Nucleotidase; D000241:Adenosine