GENISTEIN, A TYROSINE KINASE INHIBITOR, BLOCKS THE 2ND WINDOW OF PROTECTION 48 H AFTER ISCHEMIC PRECONDITIONING IN THE RABBIT

We have previously reported a delayed or ''second window of protection '' against infarction 24-72 h after ischemic preconditioning in the ra bbit. This phenomenon has also been associated with the protein kinase C signalling pathway. In the present study, we expanded our investiga tion to ascertain whether protein tyrosine kinase was in anyway associ ated with this phenomenon in the rabbit heart. We found that 48 h afte r ischemic preconditioning with 4 x 5 min coronary occlusions the perc entage of myocardium infarcting within the risk zone following a 30-mi n 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 admini stration of genistein (5 mg/kg), a tyrosine kinase inhibitor, 5 min be fore ischemic preconditioning stimulus, abolished this protection (I/R = 39.0 +/- 3.4%); Genistein per se had no significant effect on infar ction 48 h later. Risk zone Volume after coronary ligation was not sig nificantly different between intervention groups. There were no differ ences in hemodynamic parameters between groups throughout the experime ntal period. We conclude that the second window of protection, 48 h af ter preconditioning, is mediated by tyrosine kinase activation in the rabbit heart. (C) 1997 Academic Press Limited.