Original ArticleInhibition of p38 MAPK During Ischemia, But Not Reperfusion, Effectively Attenuates Fatal Arrhythmia in Ischemia/Reperfusion HeartSurinkaew, Sirirat BSc*; Kumphune, Sarawut PhD*,†; Chattipakorn, Siriporn DDS, PhD*,‡; Chattipakorn, Nipon MD, PhD*Author Information *Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand †Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok, Thailand ‡Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand. Reprints: Nipon Chattipakorn, MD, PhD, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand (e-mail: email@example.com). Supported by grants from the Thailand Research Fund through the Royal Golden Jubilee PhD Program (S.S., N.C.), TRF-Senior Research Scholar RTA5580006 (N.C.), BRG 5480003 (S.C.), and MRG5480017 (S.K.). S. Surinkaew and S. Kumphune contributed equally in this work. Received July 17, 2012 Accepted October 17, 2012 Journal of Cardiovascular Pharmacology: February 2013 - Volume 61 - Issue 2 - p 133-141 doi: 10.1097/FJC.0b013e318279b7b1 Buy Metrics Abstract Abstract: The mitogen-activated protein kinases (MAPKs) play an important role in ischemia/reperfusion (I/R) injury. Previous evidence suggests that p38 MAPK inhibition before ischemia is cardioprotective. However, whether p38 MAPK inhibition during ischemia or reperfusion provides cardioprotection is not well known. We tested the hypothesis that p38 MAPK inhibition at different times during I/R protects the heart from arrhythmias, reduces the infarct size, and attenuates ventricular dysfunction. Adult Wistar rats were subject to a 30-minute left anterior descending coronary artery occlusion, followed by a 120-minute reperfusion. A p38 MAPK inhibitor, SB203580, was given intravenously before left anterior descending coronary artery occlusion, during ischemia, or at the onset of reperfusion. The results showed that SB203580 given either before or during ischemia, but not at the onset of reperfusion, decreased the ventricular tachycardia/ventricular fibrillation (VT/VF) incidence and heat shock protein 27 phosphorylation, and increased connexin 43 phosphorylation. The infarct size and cytochrome c level was decreased in all SB203580-treated rats, without the alteration of the total Bax/Bcl-2 expression. The ventricular function was improved only in SB203580-pretreated rats. These findings suggest that timing of p38 MAPK inhibition with respect to onset of ischemia is an important determinant of therapeutic efficacy. © 2013 Lippincott Williams & Wilkins, Inc.