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Genistein, a tyrosine kinase inhibitor, blocks the ''Second window of protection'' 48 h after ischemic preconditioning in the rabbit

Imagawa, J; Baxter, GF; Yellon, DM; (1997) Genistein, a tyrosine kinase inhibitor, blocks the ''Second window of protection'' 48 h after ischemic preconditioning in the rabbit. J MOL CELL CARDIOL , 29 (7) 1885 - 1893.

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Abstract

We have previously reported a delayed or ''second window of protection'' against infarction 24-72 h after ischemic preconditioning in the rabbit. This phenomenon has also been associated with the protein kinase C signalling pathway. In the present study, we expanded our investigation to ascertain whether protein tyrosine kinase was in anyway associated with this phenomenon in the rabbit heart. We found that 48 h after ischemic preconditioning with 4 x 5 min coronary occlusions the percentage of myocardium infarcting within the risk zone following a 30-min coronary occlusion and 120-min reperfusion (IIR) was reduced from 39.6 +/- 3.3% to 18.0 +/- 3.7% (P < 0.01). However, an i.v. bolus administration of genistein (5 mg/kg), a tyrosine kinase inhibitor, 5 min before ischemic preconditioning stimulus, abolished this protection (I/R = 39.0 +/- 3.4%); Genistein per se had no significant effect on infarction 48 h later. Risk zone Volume after coronary ligation was not significantly different between intervention groups. There were no differences in hemodynamic parameters between groups throughout the experimental period. We conclude that the second window of protection, 48 h after preconditioning, is mediated by tyrosine kinase activation in the rabbit heart. (C) 1997 Academic Press Limited.

Type:Article
Title:Genistein, a tyrosine kinase inhibitor, blocks the ''Second window of protection'' 48 h after ischemic preconditioning in the rabbit
Keywords:ischemic preconditioning, second window of protection, tyrosine kinase, genistein, myocardial infarction, rabbit, SMOOTH-MUSCLE CELLS, SUBLETHAL ISCHEMIA, MYOCARDIAL PROTECTION, ADENOSINE RECEPTOR, DEXAMETHASONE, INVOLVEMENT, INFARCTION, CHANNEL
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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