Abstract 15954: Heterogeneity of Activation Rate Across LV Free Wall During Human VF and KATP Channel Expression Heterogeneity.
Background: In humans during the global ischemia that ensues after ventricular fibrillation (VF) onset a dominant frequency (DF) gradient develops across the LV wall. The mechanism of this gradient is unknown.
Hypothesis: Here we tested the hypothesis that this DF gradient across the LV wall during acute ischemia is caused by differential activation of KATP channels between epicardium and endocardium.
Methods: Electrical mapping of the langendorff perfused explanted human hearts (n=5) was performed. Acute ischemia was induced by halting the perfusion to the heart. VF was initiated and recorded for 20 seconds each at the onset and after 180 seconds, after which hearts were reperfused and defibrillated. This process was repeated after the administration of 10µM Glibenclamide. DF was computed by Welch periodogram method as reported previously. Left ventricular samples were dissected from mid-endocardial and epicardial surfaces (n=5). The relative expression of each KATP subunit gene versus β-actin was computed.
Results: The mean DF was 4.43 ± 0.05 Hz and 4.45 ± 0.04 Hz during early VF and 2.63 ± 0.04 Hz and 3.07 ± 0.02 Hz during late VF before Glibenclamide, and 3.18 ± 0.04 and 3.38 ± 0.04 during early VF, and 1.93 ± 0.04 and 1.93 ± 0.03 during late VF after Glibenclamide, in epicardium and endocardium respectively. The difference between epicardium and endocardium during late VF was statistically significant before glibenclamide (p<0.05) and not significant after Glibenaclamide (p=0.9). For the gene expression analysis, the data was normalized to LV endocardium hence the mean level of all KATP subunits in LV endocardium was 100 with no standard error. All subunits were less expressed in LV epicardium compared to LV endocardium. The mean expression levels in LV epicardium were 62 ± 10% (p<0.02), 59 ± 13% (p<0.03), 57 ± 11% (p<0.016) and 72 ± 5% (p<0.004) for Kir6.1, Kir6.2, SUR1 and SUR2A respectively.
Conclusion: During acute ischemia, the DF gradient between LV epicardium and endocardium is attenuated by Glibenclamide, a KATP blocker. The gene expression of all KATP subunits is significantly greater in endocardium compared to epicardium. Taken together these findings suggest that KATP channel expression heterogeneity may contribute to this DF gradient.
- © 2010 by American Heart Association, Inc.