Increased in vivo perpetuation of whole-heart ventricular arrhythmia in heterozygous Na + /Ca 2+ exchanger knockout mice.
| Autor: | Bögeholz N; Department of Cardiology II - Electrophysiology, University Hospital Münster, Münster, Germany.; Department of Cardiology, Schuechtermann-Klinik, Bad Rothenfelde, Germany., Knappe V; Department of Internal Medicine II, University Hospital Bonn, Bonn, Germany., Pauls P; Institute of Pharmacology and Toxicology, University Hospital Münster, Münster, Germany., Schulte JS; Institute of Pharmacology and Toxicology, University Hospital Münster, Münster, Germany., Goldhaber JI; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Müller FU; Institute of Pharmacology and Toxicology, University Hospital Münster, Münster, Germany., Nickenig G; Department of Internal Medicine II, University Hospital Bonn, Bonn, Germany., Eckardt L; Department of Cardiology II - Electrophysiology, University Hospital Münster, Münster, Germany., Schrickel JW; Department of Internal Medicine II, University Hospital Bonn, Bonn, Germany., Beiert T; Department of Internal Medicine II, University Hospital Bonn, Bonn, Germany. |
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| Jazyk: | angličtina |
| Zdroj: | International journal of cardiology. Heart & vasculature [Int J Cardiol Heart Vasc] 2022 Dec 30; Vol. 44, pp. 101168. Date of Electronic Publication: 2022 Dec 30 (Print Publication: 2023). |
| DOI: | 10.1016/j.ijcha.2022.101168 |
| Abstrakt: | Aims: Na + /Ca 2+ exchanger (NCX) upregulation in cardiac diseases like heart failure promotes as an independent proarrhythmic factor early and delayed afterdepolarizations (EADs/DADs) on the single cell level. Consequently, NCX inhibition protects against EADs and DADs in isolated cardiomyocytes. We here investigate, whether these promising cellular in vitro findings likewise apply to an in vivo setup. Methods/results: Programmed ventricular stimulation (PVS) and isoproterenol were applied to a murine heterozygous NCX-knockout model (KO) to investigate ventricular arrhythmia initiation and perpetuation compared to wild-type (WT). KO displayed a reduced susceptibility towards isoproterenol-induced premature ventricular complexes. During PVS, initiation of single or double ectopic beats was similar between KO and WT. But strikingly, perpetuation of ventricular tachycardia (VT) was significantly increased in KO (animals with VT - KO: 82 %; WT: 47 %; p = 0.0122 / median number of VTs - KO: 4.5 (1.0, 6.25); WT: 0.0 (0.0, 4.0); p = 0.0039). The median VT duration was prolonged in KO (in s; KO: 0.38 (0.19, 0.96); WT: 0.0 (0.0, 0.60); p = 0.0239). The ventricular refractory period (VRP) was shortened in KO (in ms; KO: 15.1 ± 0.7; WT: 18.7 ± 0.7; p = 0.0013). Conclusions: Not the initiation, but the perpetuation of provoked whole-heart in vivo ventricular arrhythmia was increased in KO. As a potential mechanism, we found a significantly reduced VRP, which may promote perpetuation of reentrant ventricular arrhythmia. On a translational perspective, the antiarrhythmic concept of therapeutic NCX inhibition seems to be ambivalent by protecting from initiating afterdepolarizations but favoring arrhythmia perpetuation in vivo at least in a murine model. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2022 The Authors. Published by Elsevier B.V.) |
| Databáze: | MEDLINE |
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