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- W1978052189 abstract "In ischemic preconditioning a preliminary 5-min coronary occlusion is capable of reducing the extent of myocardial infarction after a subsequent prolonged coronary occlusion. This remarkable endogenous protection is triggered by release of adenosine during the brief ischemic period. Occupied adenosine receptors couple to pertussis toxin-senstive G proteins that in turn activate phospholipase C, leading to membrane phospholipid metabolism and release on diacylglycerol. The latter leads to stimulation of protein kinase C (PKC), presumably by cadsing translocation of inactive cytosolic enzyme to the cell membranes, where it resides in its activated state. As long as PKC is resident in the membranes approximately 1 hour in rabbits the cell is in the preconditioned state and PKC is poised to act to protect the cell. If there is recurrent ischemia within that hour renewed release of adenosine reinitiates intracellular signalling with the production of more diacylglycerol. Because PKC is already in the membranes restimulation can result in almost immediate phosphorviation of critical cell constituents one of which is the yet unidentified end effector of protection. In this scheme, adenosine release occurs twice and PKC is stimulated twice—to translocate during the first ischemia and to phospherylate during the second ischemia. Other receptors such as muscarinic M2 angiotensin ± AT2 α1-adrenergic, and bradykinin B2 are also known to couple to PKC. Exogenous administration of any of these in new of the brief ischemia can also precondition rabbit myocardium, Chronic receptor stimulation by exogenous administration of an adenosine analogue result in receptor downregulation and loss of the ability to protect the myocardium with additional adenosine analogue infusion. Therefore, clinical application must await development of an agent that can initiate the protection cascade without the development of tolerance. But this preconditioning phenomenon is the first described technique of clear and unequivocal salvage of ischemic myocardium and as such it holds great promise." @default.
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- W1978052189 date "1995-05-01" @default.
- W1978052189 modified "2023-09-26" @default.
- W1978052189 title "Preconditioning During Ischemia" @default.
- W1978052189 doi "https://doi.org/10.1097/00045415-199505000-00003" @default.
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