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2 Division of Cardiology, Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298; 1 Department of Cardiology, Kanazawa Medical University, Daigaku, Uchinada, Kahoku, Ishikawa 920-0293, Japan; and 3 Corixa Corporation, Hamilton, Montana 59840
We investigated the role of tyrosine kinase (TK) signaling in the opening of the ATP-sensitive K+ (KATP) channel and 72-kDa heat shock protein (HSP72) expression during late preconditioning. Rabbits were subjected to surgical operation (sham) or were preconditioned (PC) with four cycles of 5 min of ischemia and 10 min of reperfusion. Twenty-four hours later, animals were subjected to 30 min of ischemia and 180 min of reperfusion. Genistein (1 mg/kg ip) was used to block the receptor TK. Six groups were studied: control, sham, genistein-sham, PC, genistein-PC, and vehicle-PC group (1% dimethyl sulfoxide). Genistein or vehicle was given 30 min before the surgical procedure. Genistein pretreatment decreased the expression of HSP72 in PC hearts and suppressed action potential duration shortening during ischemia in sham and PC groups. Infarct size (%risk area) was reduced in the PC (11.6 ± 1.0%) and vehicle-PC (19.3 ± 2.0%) compared with the control (40.0 ± 3.8%) or sham (46.0 ± 2.0%) groups (P < 0.05). Genistein pretreatment increased infarct size to 46.4 ± 4.1% in the PC hearts. We conclude that TK signaling is involved in KATP channel opening and HSP72 expression during late PC.
genistein; adenosine 5'-triphosphate-sensitive potassium channel; ischemia-reperfusion; 72-kDa heat shock protein
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