Premium
Mitochondrial uncouplers trigger ventricular fibrillation in isolated rat hearts
Author(s) -
ClementsJewery Hugh
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.622.2
Subject(s) - ventricular fibrillation , ischemia , cardiology , depolarization , medicine , mitochondrial permeability transition pore , perfusion , anesthesia , mptp , chemistry , programmed cell death , apoptosis , biochemistry , dopaminergic , dopamine
Sudden cardiac death due to ventricular fibrillation (VF) is a major cause of mortality in the US. The purpose of this study was to investigate the role of mitochondrial depolarization on development of VF during myocardial ischemia. Rat hearts (n=8 per group) were perfused with a modified Krebs solution. After 5 minutes, the perfusion solution was switched to one containing drug vehicle (0.01% DMSO v/v), 0.3μM CCCP, 100μM 2,4‐dinitrophenol, 0.2μM cyclosporine A or 100μM 5‐hydroxydecanoate. After a further 10 minutes, the left main coronary artery was occluded. CCCP and 2,4 dinitrophenol triggered VF in 100% of hearts prior to induction of ischemia, whereas no control heart developed VF in this period (p<0.05). In all cases VF was preceded by QT shortening (e.g. from 49±2 ms 1 min before switch to CCCP to 34±3 ms 5 min after switch to CCCP; p<0.05). During ischemia, neither cyclosporine A (88% VF) nor 5‐hydroxydecanoate (100% VF) reduced the incidence of VF compared to control (100% VF; p>0.05). In addition, neither drug affected the time to onset or the total duration of VF. In conclusion, mitochondrial depolarization is a powerful trigger for VF, and may underlie the mechanism by which VF is triggered during ischemia. Activation of the mitochondrial K ATP channel or permeability transition pore is unlikely to underlie mitochondrial depolarization or VF during myocardial ischemia. Supported by a WVSOM intramural grant.