دورية أكاديمية

Lack of authentic atrial fibrillation in commonly used murine atrial fibrillation models.

التفاصيل البيبلوغرافية
العنوان: Lack of authentic atrial fibrillation in commonly used murine atrial fibrillation models.
المؤلفون: Fu F; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Pietropaolo M; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Cui L; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Pandit S; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Li W; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Tarnavski O; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Shetty SS; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Liu J; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Lussier JM; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Murakami Y; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Grewal PK; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Deyneko G; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Turner GM; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Taggart AKP; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Waters MG; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Coughlin S; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America., Adachi Y; Cardiovascular and Metabolic Diseases, Novartis Institutes for BioMedical Research, Inc. Cambridge, Massachusetts, United State of America.
المصدر: PloS one [PLoS One] 2022 Jan 07; Vol. 17 (1), pp. e0256512. Date of Electronic Publication: 2022 Jan 07 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Disease Models, Animal*, Atrial Fibrillation/*physiopathology, AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Animals ; Atrial Flutter/physiopathology ; Atrial Function, Left/physiology ; Atrial Remodeling ; Carbachol/pharmacology ; Cardiac Pacing, Artificial/adverse effects ; Electrocardiography ; Mice ; Mice, Inbred C57BL ; Myocardium/pathology ; Myocytes, Cardiac/pathology ; Tachycardia, Ventricular/physiopathology
مستخلص: The mouse is a useful preclinical species for evaluating disease etiology due to the availability of a wide variety of genetically modified strains and the ability to perform disease-modifying manipulations. In order to establish an atrial filtration (AF) model in our laboratory, we profiled several commonly used murine AF models. We initially evaluated a pharmacological model of acute carbachol (CCh) treatment plus atrial burst pacing in C57BL/6 mice. In an effort to observe micro-reentrant circuits indicative of authentic AF, we employed optical mapping imaging in isolated mouse hearts. While CCh reduced atrial refractoriness and increased atrial tachyarrhythmia vulnerability, the left atrial (LA) excitation patterns were rather regular without reentrant circuits or wavelets. Therefore, the atrial tachyarrhythmia resembled high frequency atrial flutter, not typical AF per se. We next examined both a chronic angiotensin II (Ang II) infusion model and the surgical model of transverse aortic constriction (TAC), which have both been reported to induce atrial and ventricular structural changes that serve as a substrates for micro-reentrant AF. Although we observed some extent of atrial remodeling such as fibrosis or enlarged LA diameter, burst pacing-induced atrial tachyarrhythmia vulnerability did not differ from control mice in either model. This again suggested that an AF-like pathophysiology is difficult to demonstrate in the mouse. To continue searching for a valid murine AF model, we studied mice with a cardiac-specific deficiency (KO) in liver kinase B1 (Cardiac-LKB1), which has been reported to exhibit spontaneous AF. Indeed, the electrocardiograms (ECG) of conscious Cardiac-LKB1 KO mice exhibited no P waves and had irregular RR intervals, which are characteristics of AF. Histological evaluation of Cardiac-LKB1 KO mice revealed dilated and fibrotic atria, again consistent with AF. However, atrial electrograms and optical mapping revealed that electrical activity was limited to the sino-atrial node area with no electrical conduction into the atrial myocardium beyond. Thus, Cardiac-LKB1 KO mice have severe atrial myopathy or atrial standstill, but not AF. In summary, the atrial tachyarrhythmias we observed in the four murine models were distinct from typical human AF, which often exhibits micro- or macro-reentrant atrial circuits. Our results suggest that the four murine AF models we examined may not reflect human AF well, and raise a cautionary note for use of those murine models to study AF.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: all authors are current or past fulltime employee of Novartis Institutes Biomedical Research, Inc.
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المشرفين على المادة: 8Y164V895Y (Carbachol)
EC 2.7.11.1 (Stk11 protein, mouse)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
تواريخ الأحداث: Date Created: 20220107 Date Completed: 20220211 Latest Revision: 20220211
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8741011
DOI: 10.1371/journal.pone.0256512
PMID: 34995278
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0256512