p38 MAPK activity is not increased early during sustained coronary artery occlusion in preconditioned versus control rabbit heart.
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.
Gysembergh
A
A
Heart Institute, Good Samaritan Hospital and Department of Medicine, University of California, Los Angeles, CA 90017-2395, USA.
Simkhovich
B Z
BZ
Kloner
R A
RA
Przyklenk
K
K
D000818:Animals; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000201:enzymology*; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580