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0291 : Mitochondrial permeability transition pore opening might contribute to ventricular arrhythmia maintenance
- Source :
- Archives of Cardiovascular Diseases Supplements. 8:208
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Background Calcium leak from the sarcoplasmic reticulum (SR) favors cardiac sudden death through a calcium overload mechanism. Here we investigate the crosstalk between the calcium overload SR-mediated and the mitochondrial permeability transition pore (mPTP) opening during a ventricular arrhythmic episode. Methods and results a burst pacing protocol was developed to induce ventricular arrhythmia in the perfused rat heart. Surface electrocardiogram, left ventricular pressure, and oxygen consumption were monitored. Epicardial fluorescence was recorded from either a mitochondrial membrane potential dye or an intracellular calcium dye. ECG signals were used to assess both arrhythmia complexity and duration. Hearts were perfused with tacrolimus (FK506) alone or in combination with cyclosporin A (CsA) to promote SR calcium leak or inhibit mPTP, respectively. Prior to arrhythmia induction, FK506 promoted mitochondrial depolarization and intracellular calcium overload in a CsA-sensitive manner. More than 90% of hearts developed complex ventricular arrhythmias in the FK506 group and this was accompanied by a strong mitochondrial membrane depolarization. In contrast, in the FK506 + CsA group, 100% of the hearts spontaneously defibrillate after a few seconds of arrhythmias. In this group, following arrhythmia induction, mitochondrial depolarization amplitude, intracellular calcium overload and heart efficiency depression was decreased in comparison to the FK506 group. Conclusions Here we suggest that the FK506-induced calcium overload promotes mitochondrial calcium accumulation and leads to mPTP opening. We propose that mPTP opening should be considered as an arrhythmogenic substrate. The author hereby declares no conflict of interest
- Subjects :
- Membrane potential
medicine.medical_specialty
business.industry
MPTP
chemistry.chemical_element
Depolarization
Calcium
Calcium in biology
chemistry.chemical_compound
Mitochondrial permeability transition pore
chemistry
Internal medicine
Cyclosporin a
cardiovascular system
medicine
Ventricular pressure
Cardiology
cardiovascular diseases
Cardiology and Cardiovascular Medicine
business
Subjects
Details
- ISSN :
- 18786480
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Archives of Cardiovascular Diseases Supplements
- Accession number :
- edsair.doi.dedup.....168ed7d282c175813b5bc9e671809917
- Full Text :
- https://doi.org/10.1016/s1878-6480(16)30379-2