CELLULAR MECHANISMS IN ISCHEMIC PRECONDITIONING - THE ROLE OF ADENOSINE AND PROTEIN-KINASE-C
CELLULAR MECHANISMS IN ISCHEMIC PRECONDITIONING - THE ROLE OF ADENOSINE AND PROTEIN-KINASE-C
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DOI：
10.1111/j.1749-6632.1994.tb36719.x
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发表时间：
1994-01-01
期刊：
影响因子：
--
通讯作者：
LIU, YG
中科院分区：
文献类型：
--
作者：
DOWNEY, JM;COHEN, MV;LIU, YG
For several decades there has been a concerted research effort to identify interventions that could make the heart more resistant to ischemia. While it is now possible with thrombolytic therapy to restore perfusion to ischemic regions of the heart in the patient with acute myocardial infarction, reperfusion can seldom be accomplished before a substantial amount of myocardial necrosis has occurred. To date no such therapy is clinically available. Antioxidants, calcium antagonists, and beta blockers have all been tested but have failed to provide consistent protection in preclinical trials.'-3 This experience raised questions as to whether it was even possible to render the myocytes more resistant to a transient ischemic insult. Recent studies with ischemic preconditioning, however, reveal that it is indeed possible to make the myocyte tolerant to ischemia. Muny and colleagues in 1987 reported that preconditioning the heart with four brief periods of ischemia, each 5 min in duration, caused the heart to tolerate a subsequent 45-min ischemic insult with only a fraction of the infarction realized in nonpreconditioned hearts. 4 If the mechanism of this adaptive response can be understood, it should theoretically be possible to institute this form of protection pharmacologically in the coronary artery disease patient. Ischemic preconditioning is a potent protector of the reperfused heart and its efficacy has been repeatedly confirmed. We5 and others6 have shown that as little as a single 5-min period of coronary occlusion could invoke full protection and that the anti-infarct effect lasts for up to an hour. 5.7 In most models of ischemic preconditioning the protection is roughly equivalent to that which would result from shortening the ischemic period by about 20 min. While the exact mechanism of this protection remains a mystery, there is mounting evidence from this and other laboratories that adenosine plays an important role in this phenomenon. Adenosine has been the focus of studies of the heart for many years but only recently has adenosine been proposed to have direct cardioprotective effects. This concept was first proposed by Ely and colleagues8 and today the number of papers describing adenosine-mediated protection seems to be increasing geometrically. It was against that background that we thought to test adenosine as a possible mediator of ischemic preconditioning.
