Key result
Genistein increases infarct size ~4-fold in preconditioned rabbit hearts, implicating tyrosine kinase in late preconditioning.
Why the study?
The role of tyrosine kinase signaling in ATP-sensitive K(+) channel opening and HSP72 expression during late preconditioning was unclear.
Absolute Event Rate: 46.4% vs 11.6%
Tyrosine kinase signaling is essential for K(ATP) channel opening and HSP72 expression during late preconditioning, as its blockade abolishes cardioprotection against ischemia-reperfusion injury.
Tyrosine kinase inhibition abolishes late preconditioning cardioprotection in rabbits; leaves open translation to human ischemia-reperfusion injury.
We investigated the role of tyrosine kinase (TK) signaling in the opening of the ATP-sensitive K(+) (K(ATP)) 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 K(ATP) channel opening and HSP72 expression during late PC.
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Okubo et al. (2000) studied Ischemia/reperfusion injury. Genistein vs. Vehicle (1% dimethyl sulfoxide) or no genistein was evaluated on Infarct size (% risk area). Genistein pretreatment increased infarct size to 46.4% in preconditioned rabbit hearts compared to 11.6% in preconditioned controls, indicating tyrosine kinase signaling is involved in late preconditioning.
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