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The Role of KATP-channels in the Maintenance of Ventricular Fibrillation in Cardiomyopathic Human Hearts

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.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32237
Date21 March 2012
CreatorsFarid, Talha
ContributorsNanthakumar, Kumaraswamy, Dorian, Paul
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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