Key Points
- To examine whether pharmacological inhibition of p38-MAPK with SB203580 delays ischemic cell death and interacts with ischemic preconditioning in pig myocardium.
- Administered SB203580 via local intracoronary infusion (60 min) or systemic infusion (10 min) before a 60-min coronary occlusion followed by 60-min reperfusion in an in vivo pig model.
- Assessed myocardial infarct size, p38-MAPK phosphorylation (Thr180/Tyr182), in-gel p38-MAPK kinase activity, and nuclear activating transcription factor 2 (ATF-2) phosphorylation.
- Evaluated the effect of local and systemic SB203580 infusion on infarct size reduction achieved by ischemic preconditioning.
- Local infusion of SB203580 decreased myocardial infarct size from 69.3 ± 2.7% in controls to 36.8 ± 3.7%, while systemic infusion reduced infarct size to 36.1 ± 5.6%.
- Systemic SB203580 reduced p38-MAPK phosphorylation and enzymatic activity at 30 and 45 minutes of ischemia, and significantly inhibited nuclear ATF-2 phosphorylation without altering total ATF-2 abundance.
- Infusion of SB203580 before and during ischemic preconditioning did not alter the cardioprotection or infarct size reduction mediated by preconditioning.
Structured PICO
Does SB203580 reduce infarct size in a pig model of myocardial ischemia?
PPopulationPig in vivo model of myocardial ischemia (60-min coronary occlusion followed by 60-min reperfusion)
IInterventionSB203580 (p38-MAPK inhibitor) via local infusion for 60 min or systemic infusion for 10 min before ischemia
CComparatorControl (Krebs-Henseleit buffer)
OOutcomeInfarct sizesurrogate
Inhibition of the p38-MAPK pathway with SB203580 significantly reduces infarct size in a pig model of myocardial ischemia-reperfusion injury.