Abstract 9418: Selective p38 Inhibitor Administered During Ischemia, but Not Reperfusion, Effectively Attenuates Fatal Arrhythmia in Rats with Ischemia/Reperfusion Injury
p38 mitogen-activated protein kinase (p38) has been shown to play an important role in facilitating myocardial infarction process in ischemia/reperfusion (I/R) injury. Inhibition of p38 prior to ischemia has been shown as cardioprotective. However, the benefit of inhibition of p38 after ischemia or during reperfusion is unknown. We tested the hypothesis that inhibition of p38 at different times during I/R can attenuate ventricular fibrillation (VF) incidence and reduce the infarct size.
Methods: Adult Wistar rats were subject to 30-min left anterior descending coronary artery (LAD) occlusion, followed by 120-min reperfusion. A p38 inhibitor, SB203580, was given intravenously (2-mg/kg) either at 15 minutes before ischemia (pretreatment group), 15 minutes after LAD occlusion (ischemia group), or at onset of reperfusion. Saline was used as a vehicle in each group. Electrocardiogram was recorded and the arrhythmia score was analyzed based on the frequency and duration of arrhythmias detected (1 is lowest and 5 was highest arrhythmia incidence). The infarct size was determined in each heart.
Results: SB203580 given before LAD occlusion and during ischemia significantly decreased the overall arrhythmia score and the incidence of VT/VF, compared with the vehicle-treated group (Figure). However, SB203580 given at onset of reperfusion did not show this benefit. The time to VT/VF onset was not changed for SB203580 treated at any time, compared to the vehicle. Unlike arrhythmia incidence, the infarct size was markedly decreased in SB203580-treated rats in all groups.
Conclusion: Although SB203580 could markedly decrease the infarct size when administered before or after LAD occlusion, as well as during reperfusion, it could only effectively attenuate the fatal arrhythmias when given only prior to LAD occlusion and during ischemia. These findings indicate the crucial role of the timing of p38 inhibition in preventing fatal arrhythmia in an I/R model.
- © 2011 by American Heart Association, Inc.