Genistein, a tyrosine kinase inhibitor, blocks the "second 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 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 any way associated with this phenomenon in the rabbit heart. We found that 48 h after ischemic preconditioning with 4x5 min coronary occlusions the percentage of myocardium infarcting within the risk zone following a 30-min coronary occlusion and 120-min reperfusion (I/R) 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.
Imagawa
J i
Ji
The Hatter Institute for Cardiovascular Studies, University College London Hospital and Medical School, Grafton Way, London, WC1E 6DB, UK.
Baxter
G F
GF
Yellon
D M
DM
D000818:Animals; D001794:Blood Pressure; D001831:Body Temperature; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein; D006339:Heart Rate; D006439:Hemodynamics; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D015427:Reperfusion Injury / Q000201:enzymology; D015398:Signal Transduction; D013997:Time Factors
D004791:Enzyme Inhibitors; D007529:Isoflavones; D019833:Genistein; D011505:Protein-Tyrosine Kinases