Abstract 1431: SUR1 Knockout Mice are Protected Against Myocardial Ischemia-Reperfusion Injury
Background: SUR1 is a regulatory subunit of ATP-sensitive K+ channels (KATP), best characterized in pancreatic B-cells. We have previously reported that SUR1 mRNA is expressed in cardiac tissue and that its expression is up-regulated during postnatal development. Using immunocytochemistry approaches we found SUR1 protein to be present at the sarcolemmmal surface of cardiac myocytes. The physiological role of SUR1 in the heart remains unknown. Since KATP channels are widely implicated in the protective pathways of myocardial ischemic preconditioning, we investigated the role of SUR1 in an in vivo model of myocardial ischemia-reperfusion injury.
Methods: Systemic SUR1 knockout mice (SUR1−/−) and wild-type controls (WT) were subjected to 30 min of LCA occlusion and reperfusion. High-resolution echocardiography was performed before ischemia (BASE) and 7 days following reperfusion (POST).
Results: Baseline cardiac function was unaltered in the SUR1−/− mice. However, SUR1−/−exhibited improvements in both LV function (fractional shortening and ejection fraction) and dimensions (LVEDD and LVESD) post myocardial infarction. WT mice displayed a 28% increase in LVESD post MI compared to a 2% increase in SUR1−/− mice. In correlation, LV fractional shortening was significantly preserved in SUR1−/− mice vs. WT (29.3% vs. 16.9%).
Conclusions: These results suggest that SUR1 ablation may improve post-MI LV function and protect against unfavorable post-ischemic LV remodeling (dilatation). Future studies are needed to further define the role of SUR1 in MI-R and it’s role in regulating myocardial KATP channels.