Increased fibroblast accumulation in the equine heart following persistent atrial fibrillation

Saljic, Arnela; Fenner, Merle Friederike; Winters, Joris; Flethøj, Mette; Eggertsen, Caroline Eggert; Carstensen, Helena; Nissen, Sarah Dalgas; Hesselkilde, Eva Melis; Hunnik, Arne van; Schotten, Ulrich; Sørensen, Ulrik; Jespersen, Thomas; Verheule, Sander; Buhl, Rikke

doi:10.1016/j.ijcha.2021.100842

Cited by 7 publications

(6 citation statements)

References 55 publications

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“…Tissue simulations showed that not only could the myofibroblast infiltration affect the arrhythmia vulnerability [ 73 , 74 ], but also the fibrosis pattern can play a role in the initiation and maintenance of reentrant activity [ 46 , 47 , 54 , 75 ]. Sridhar et al [ 76 ] have shown the role that fibroblast infiltration plays regarding the onset of arrhythmia due to the increase of anisotropy in the tissue.…”

Section: Discussionmentioning

confidence: 99%

Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology

Sánchez

Trénor

Sáiz

et al. 2021

Cells

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During atrial fibrillation, cardiac tissue undergoes different remodeling processes at different scales from the molecular level to the tissue level. One central player that contributes to both electrical and structural remodeling is the myofibroblast. Based on recent experimental evidence on myofibroblasts’ ability to contract, we extended a biophysical myofibroblast model with Ca2+ handling components and studied the effect on cellular and tissue electrophysiology. Using genetic algorithms, we fitted the myofibroblast model parameters to the existing in vitro data. In silico experiments showed that Ca2+ currents can explain the experimentally observed variability regarding the myofibroblast resting membrane potential. The presence of an L-type Ca2+ current can trigger automaticity in the myofibroblast with a cycle length of 799.9 ms. Myocyte action potentials were prolonged when coupled to myofibroblasts with Ca2+ handling machinery. Different spatial myofibroblast distribution patterns increased the vulnerable window to induce arrhythmia from 12 ms in non-fibrotic tissue to 22 ± 2.5 ms and altered the reentry dynamics. Our findings suggest that Ca2+ handling can considerably affect myofibroblast electrophysiology and alter the electrical propagation in atrial tissue composed of myocytes coupled with myofibroblasts. These findings can inform experimental validation experiments to further elucidate the role of myofibroblast Ca2+ handling in atrial arrhythmogenesis.

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Section: Discussionmentioning

confidence: 99%

Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology

Sánchez

Trénor

Sáiz

et al. 2021

Cells

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“…It is unknown whether the same mechanisms exist in horses. However, as myofibroblasts are relatively common in equine atria, these cells are indeed of great interest and should be investigated more closely [41].…”

Section: Triggersmentioning

confidence: 99%

“…Structural changes, such as cellular hypertrophy, cellular dedifferentiation to a precursor and interstitial fibrosis have been reported in horses with persistent AF [5,10,51,52]. Studies investigating structural changes in response to AF found an increased number of atrial fibroblasts after 6 weeks of induced AF [41] and increased atrial fibrosis after 2 months of induced AF [10].Two major inflammatory drivers involved in fibrosis formation are angiotensin II and transforming growth factor β1 (TGF-β1). These factors are heavily involved in fibrogenesis, including the transformation of fibroblasts into collagen-producing myofibroblasts, and increased tissue levels have been found in the right atrium of patients with pAF.…”

Section: Atrial Remodelingmentioning

confidence: 99%

Paroxysmal Atrial Fibrillation in Horses: Pathophysiology, Diagnostics and Clinical Aspects

Kjeldsen

Nissen

Buhl

et al. 2022

Animals

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Atrial fibrillation (AF) is the most common arrhythmia in horses causing poor performance. As in humans, the condition can be intermittent in nature, known as paroxysmal atrial fibrillation (pAF). This review covers the literature relating to pAF in horses and includes references to the human literature to compare pathophysiology, clinical presentation, diagnostic tools and treatment. The arrhythmia is diagnosed by auscultation and electrocardiography (ECG), and clinical signs can vary from sudden loss of racing performance to reduced fitness or no signs at all. If left untreated, pAF may promote electrical, functional and structural remodeling of the myocardium, thus creating a substrate that is able to maintain the arrhythmia, which over time may progress into permanent AF. Long-term ECG monitoring is essential for diagnosing the condition and fully understanding the duration and frequency of pAF episodes. The potential to adapt human cardiac monitoring systems and computational ECG analysis is therefore of interest and may benefit future diagnostic tools in equine medicine.

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“…The histology of the consecutive sections of the AV node confirmed the presence of a cartilaginous structure at the base of the aortic leaflet in conjunction with the AV node and the penetrating bundle, also known as the His bundle ( Figure 4 ). An automatic quantification method of the amount of collagen [ 17 ] revealed no obvious differences in the amount of collagen, with 83% collagen in the case horse and a mean of 82 ± 17% in the control horses. The major difference was the location of the AV node in conjunction with the cartilage.…”

Section: Case Presentationmentioning

confidence: 99%

Cartilaginous Intrusion of the Atrioventricular Node in a Quarter Horse with a High Burden of Second-Degree AV Block and Collapse: A Case Report

Nissen

Saljic

Kjeldsen

et al. 2022

Animals

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Second-degree atrioventricular (AV) block is the most common cardiac arrhythmia in horses, affecting 40–90% depending on breed. Usually, the AV blocks occur while the horses are resting and disappear upon exercise and are, therefore, considered to be uneventful for horses. However, if the AV blocks occur frequently, this may result in syncope and collapse. Identifying the cause of second-degree AV block is difficult and often subscribed to high vagal tone. In this report, we present an eight-year-old Quarter horse with a high burden of second-degree AV blocks and multiple collapses. The clinical examination, including neurological examination, blood analysis, 24-h ECG recording and cardiac echocardiography, did not reveal any signs of general or cardiovascular disease besides a high burden of second-degree AV blocks (~300 blocks per hour) and a hyperechoic area in the AV nodal region. An implantable loop recorder (ILR) was inserted to monitor the cardiac rhythm. The ILR detected several consecutive second-degree AV blocks and pauses above 5 s. However, unfortunately, no recordings were available during the collapses. Eventually, the horse was euthanized and the heart inspected. The aortic root was severely cartilaginous and appeared to penetrate the AV node, especially in the His bundle region, possibly explaining the hampered AV conduction. Nevertheless, it is still uncertain if the AV nodal disruption caused the collapses and more knowledge on AV nodal diseases in horses is warranted.

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Increased fibroblast accumulation in the equine heart following persistent atrial fibrillation

Abstract: Highlights Persistent atrial fibrillation is associated with increased fibroblast accumulation. Six weeks of persistent AF is not associated with structural remodeling. Fibroblasts are potentially contributing to alteration in atrial electrophysiology.

Cited by 7 publications

References 55 publications

Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology

Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology

Paroxysmal Atrial Fibrillation in Horses: Pathophysiology, Diagnostics and Clinical Aspects

Cartilaginous Intrusion of the Atrioventricular Node in a Quarter Horse with a High Burden of Second-Degree AV Block and Collapse: A Case Report

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