The stress-responsive MAP kinase p38 is activated by low-flow ischemia in the in situ porcine heart

Stress-responsive p38 MAP kinase is activated by phosphorylation during glo bal and severe regional myocardial ischemia. However, it is unknown whether or not moderate, low-flow ischemia also activates p38 MAP kinase. Therefor e, we investigated p38 MAP kinase activation in an established model of sho rt-term hibernation and stunning. In anesthetized swine, coronary blood Row into the left anterior descending coronary artery was decreased in order t o reduce regional contractile function by similar to 50%. Transmural myocar dial biopsies were taken before (controls) and during ischemia as well as a fter reperfusion. Creatine phosphate content, after an early ischemic reduc tion, recovered to control values at 90 min ischemia. The expression of pho spholamban, SERCA2a, calsequestrin, and troponin inhibitor was unchanged un der these conditions (Northern and Western blotting). At 8 min of ischemia, however, p38 MAP kinase was activated to 221% of the pre-ischemic value as judged by its elevated phosphorylation state, Then, it returned to control values by 85 min ischemia. We conclude that low-Row ischemia transiently a ctivates the stress-responsive p38 MAP kinase which might act to trigger ca rdioprotective events, (C) 2000 Academic Press.