- 作者：Philippe Pasdois ; philippe.pasdois@ihu-liryc.fr" class="auth_mail" title="E-mail the corresponding author ; Laurent Arsac ; Vé ; ronique Deschodt-Arsac ; Dominique Detaille ; Fanny Vaillant ; Audrey Semont ; Philippe Diolez ; Pierre Dos Santos
- 刊名：Archives of Cardiovascular Diseases Supplements
- 出版年：2016
- 出版时间：April 2016
- 年：2016
- 卷：8
- 期：3
- 页码：208
- 全文大小：48 K
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