Our aim was to test the hypothesis that cardioprotection achieved with ischemic preconditioning (PC) involves increased activity of
p38 mitogen-activated protein kinase (MAPK) early during sustained coronary artery occlusion. Using the isolated
buffer-perfused rabbit heart model of regional
ischemia, we quantified
p38 MAPK activity (pmol/min/mg
protein: by biochemical assay) at 5 and 10 min into
coronary occlusion in hearts that first received PC
ischemia or no intervention (controls), and in non-ischemic shams. Control hearts exhibited significant increases in
p38 MAPK activity, averaging 883+/-142 and 1135+/-179 at 5 and 10 min of occlusion, v 144+/-49 in shams (P<0.05 and P<0.01).
p38 MAPK activity was not, however, augmented with PC; rather, at 5 min into occlusion, activity was attenuated, averaging 432+/-72 (P=N.S. v
sham). This early, modest reduction in
p38 MAPK activity may be physiologically relevant: in additional hearts subjected to 30 min of sustained
coronary occlusion and 2 h of reperfusion,
infarct size (by tetrazolium staining: expressed as a % of the risk region) was 54+/-5% in hearts treated with
SB 203580 (confirmed in our study to inhibit
p38 MAPK activity at 5 min into occlusion)
v 70+/-5% in vehicle controls (P<0.05). Thus, cardioprotection achieved with ischemic preconditioning in rabbit heart does not involve augmentation of
p38 MAPK activity early during sustained
coronary occlusion.