Background: Modulation of ischemia-dependent pathways alters electrophysiological evolution of ventricular fibrillation(VF).
Hypothesis: 1)There is regional disease-related expression of KATP-channels in human cardiomyopathic hearts. 2)KATP-channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness(ΔERP).
Methods and Results: Electric mapping of control(n=6) and treatment(n=9) (10 μmol/L glibenclamide) isolated human cardiomyopathic hearts was performed. Spontaneous defibrillation and KATP-subunit gene expression were studied. Spontaneous VF termination occurred in 1/6 control and 7/8 treated hearts (P=0.026). After 180 seconds of ischemia, LV transmural dispersion in VF cycle length was observed(p=0.001), which was attenuated by glibenclamide. There was greater gene expression of all KATP-subunit on the endocardium compared with the epicardium(P<0.02). In ischemic rat heart model, ΔERP was verified with pacing protocols (36±5ms vs 4.9±4ms, p=0.019).
Conclusions: KATP channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of KATP channels promotes spontaneous defibrillation by attenuating ischemia-dependent ΔERP during VF.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32237 |
| Date | 21 March 2012 |
| Creators | Farid, Talha |
| Contributors | Nanthakumar, Kumaraswamy, Dorian, Paul |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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