There is debate concerning the involvement of
p38 mitogen-activated protein kinase (MAPK) in ischemic preconditioning (PC). At the center of the controversy are data obtained after administration of
SB 203580, a specific inhibitor of
p38 MAPK. Whereas several studies have reported that
SB 203580 abolishes the cardioprotective effect of PC, others claim that this compound is actually cardioprotective against
ischemia. Many of these latter observations have been made in isolated myocardial cells. Accordingly the present study was designed to test the effect of
SB 203580 in a model of preconditioning in intact rabbit hearts in which
infarct size was the end-point. Isolated hearts experienced 30 min of regional
ischemia followed by 120 min of reperfusion.
Infarct size was measured with
triphenyltetrazolium chloride. In control hearts
infarction was 30.2 +/- 3.3% of the risk zone. PC with 5 min of global
ischemia and 10 min of reperfusion before the 30-min period of
ischemia significantly reduced
infarct size to 10.2 +/- 2.4% (P < 0.05 vs. control).
SB 203580 (2 microM) added to the perfusate for 20 min starting 5 min before the index
ischemia totally blocked the protection from PC (27.4 +/- 3.3%
infarction).
SB 203580 alone had no effect on
infarct size (28.6 +/- 4.6%
infarction). These results reveal that
SB 203580 does not affect
infarct size on its own, but selectively blocks preconditioning's anti-
infarct effect in the intact rabbit heart.