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. 2026 Feb 4;21(2):e0340985. doi: 10.1371/journal.pone.0340985

Yucatan Miniswine Model of Atrial Fibrillation: Clinical Relevance

Pouria Mostafizi 1, Eli Lefkowitz 1,2, Jacob Ref 1,2, Fox Bravo 1,2, Daniel Benson 1,2,3, Deirdre O’Donnell 1,2, Kenneth Fox 1,2,4, Adrian Grijalva 1, Mary Kaye Pierce 1, Grace Gorman 1, Alice McArthur 1, Sherry Daugherty 1, Anil Shendge 5,6, Amitabh C Pandey 5,6, Jordan Lancaster 1, Jen Watson Koevary 1, Steven Goldman 1,*, Talal Moukabary 1
Editor: Kamal Sharma7
PMCID: PMC12871992  PMID: 41637443

Abstract

Introduction

Persistent atrial fibrillation (AFib) is the most common chronic arrhythmia in adults in the United States and is associated with significant morbidity, including thromboembolic events, stroke, and heart failure. Despite available therapies such as catheter ablation and antiarrhythmic drugs, AFib remains incurable for many patients. Our study aims to develop a large-animal model of AFib in Yucatan miniswine to support investigation of new therapeutic approaches for this disease.

Methods

Yucatan miniswine were selected for their physiological similarity to humans and suitable size for long-term studies. Each animal was initially fitted with an external FitBark 2.0 collar to track activity as a surrogate for quality of life. Animals then underwent implantation of an atrial pacing lead in the right atrial appendage, a pacing generator, and an insertable cardiac monitor (ICM Reveal LINQ™) implanted subcutaneously along the left scapula. One week after the pacemaker implantation, animals underwent rapid atrial pacing to induce persistent AFib. All procedures were performed in accordance with relevant institutional and regulatory guidelines.

Results

Atrial fibrillation was successfully induced in 4 of 6 animals within 80.3 ± 22.3 days of initiating pacing with three animals going into persistent AFib and one animal going into paroxysmal AFib. The definition of persistent AFib was that animals remained in AFib for more than 14 days after pacing was discontinued. Paroxysmal AFib was defined as AFib lasting less than 14 days. Activity levels decreased following persistent AFib onset, indicating a decline in overall health and quality of life. Histopathological analyses showed significant increases in fibrosis and loss of atrial cardiomyocytes after persistent AFib was induced in swine. Several anatomical and technical challenges, particularly related to vascular access and cardiac dimensions, were overcome through customized surgical strategies, including jugular venous cut-downs, lateral cervical ICM implantation, long vascular sheaths, custom styluses, and perioperative antibiotic coverage. These innovations were critical to establishing a robust and reproducible persistent AFib model.

Introduction

Atrial fibrillation (AFib) is the most common sustained cardiac arrhythmia in adults, currently affecting an estimated 2.7 million people in the United States and increasing in prevalence as populations age and cardiovascular survival improves [1]. AFib is strongly associated with stroke, heart failure, diminished functional capacity, and increased mortality, and it often exacerbates left ventricular dysfunction [2]. Once established, AFib becomes self-perpetuating with atrial stretch, inflammation, heart failure, and progressive fibrosis driving both electrical and structural remodeling, creating a substrate that promotes this persistent arrhythmia [3]. Although advances such as pulsed-field ablation and antiarrhythmic agents have improved outcomes for select patients, AFib incidence and recurrence remain high, reflecting a critical need for therapies that directly address the underlying atrial pathology, specifically fibrotic replacement of functional atrial cardiomyocytes.

Large-animal models of cardiac disease are essential for bridging mechanistic insights to clinical intervention, yet current preclinical AFib models rarely reproduce the chronicity, fibrosis, and electrophysiologic complexity observed in human disease. These limitations motivated our development of a robust, reproducible Yucatan miniswine model of AFib that more faithfully captures the human condition. Yucatan miniswine have cardiac anatomy, chamber size, conduction system organization, and fibrotic remodeling patterns that closely mirror those of humans, making them ideal for translational arrhythmia research.

Here, we describe a novel miniswine model of AFib designed to enable longitudinal monitoring, mechanistic study, and therapeutic testing. A unique aspect of our work is the inclusion of continuous electrocardiographic recordings obtained via implanted internal cardiac monitors (ICMs) to confirm arrhythmia induction, track AFib burden, and document persistence over time. In parallel, FitBark activity trackers were used to quantify behavioral and functional changes in the animals between sinus rhythm and AFib, adding clinically relevant physiologic endpoints. Together, these tools create a comprehensive platform that recapitulates key clinical features of human AFib and provides a rigorous foundation for evaluating new interventions that potentially target atrial fibrosis the underlying cause of the disease.

Materials and methods

Animal studies, ethical considerations

All animal work was conducted under the oversight of the University of Arizona Institutional Animal Care and Use Committee (IACUC) and the University of Arizona Animal Care (UAC) veterinary staff. The IACUC oversees the university’s animal care and use program and is responsible for reviewing and approving all activities involving vertebrate animals for research, teaching, and testing. Compliance information includes USDA, Class R Research Facility, Registration Number: 86-R-0003, NIH/OLAW Assurance Number: D16-00159, and AAALAC International Accreditation since 1969, Accreditation Number: 000163, Status: Continued Full Accreditation. Animals were observed at least once daily, with increased monitoring following surgical procedures. The protocol described in this peer-reviewed article is published on protocols.io, DOI: x.doi.org/10.17504/protocols.io.yxmvm1p76v3p/v1 and is included for printing as supporting information file 1 with this article.

Animal preparation

Approximately one-year-old Yucatan miniswine (N = 6) were enrolled in this study. All procedures were approved by the Institutional Animal Care and Use Committee (IACUC) and adhered to ARRIVE guidelines. Animals were housed in a temperature-controlled facility with a 12-hour light-dark cycle. Standard diets and ad libitum water access were provided in the enriched environment to promote well-being. The study adhered to USDA and AWA regulations, and all efforts were made to minimize animal distress.

Anesthesia and surgical approach

Anesthesia was induced using ketamine (11–33 mg/kg IM) and/or midazolam (0.1–0.5 mg/kg IM). Isoflurane (1−3%) was administered for maintenance anesthesia for the duration of the procedure. Animals were administered buprenorphine Sr 0.12–0.27 mg/kg for minimizing pain and distress after surgical implantation of the pacing device. Standard aseptic techniques were followed during surgical preparation. The ICM was implanted subcutaneously in the left chest. For pacemaker implantation, the right external jugular vein was accessed using a cutdown with preemptive loose ligation to minimize bleeding. Custom elongated sheaths and stylus shapes were used to position the pacing atrial lead in the right atrial appendage. A Medtronic CRT-P device was implanted subcutaneously in a small pocket in the right chest. Proper lead placement was confirmed with a multi-lead ECG.

Pacing protocol: Pacemaker activation

The pacemaker was activated one-week post-implantation. Rapid atrial pacing was initiated at 400 bpm (150 ms cycle length). If AFib was not sustained, the pacing rate was gradually increased to 600 bpm (100-ms cycle length) in 10-ms increments. The ICM Device, the pacemaker generator, the programmer (Medtronic 2090), and Medtronic CareLink Encore are shown in Fig 1. An illustration of how all these devices work together in the swine model is shown in Fig 2. Activity levels were tracked 24/7 with the FitBark activity collars show in Fig 3.

Fig 1. Medical Devices.

Fig 1

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(A) Internal Cardiac Monitor Device. (B) Pacemaker Device. (C) Programmer (Medtronic 2090) sets regular, rapid atrial overdrive pacing parameters on the pacemaker (400-600 bpm, 8V). (D) The programmer (Medtronic CareLink Encore) is used to record frozen strips and episodes from the Internal Cardiac Monitor, which constitutes Internal Cardiac Monitor reports.

Fig 2. Medtronic Rapid Atrial Pacing System.

Fig 2

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A pacing wire is inserted into the right atrial appendage and connected to a pacing generator implanted in the lateral neck wall muscle. A programmer, Medtronic CareLink 2090, controlled the pacing generator and internal cardiac monitor wirelessly. https://biorender.com/mngrgm4.

Fig 3. Activity Level Monitoring.

Fig 3

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Activity levels 24/7 were tracked using Fitbark collars worn by the swine as illustrated above.

Euthanasia

Animals were euthanized at endpoints via potassium chloride injection under deep anesthesia. Authorization was confirmed with no heartbeat on the ECG, prior to tissue harvest/necropsy.

Histology

Cardiac biopsies were taken from the left and right atrium, fixed in 10% formalin and paraffin embedded before undergoing histopathological evaluation. Specimens were fixed in 10% neutral buffered formalin, transferred to 70% ethanol, and processed for paraffin embedding and sectioning. Histologic sections were stained with Masson’s trichrome to assess myocardial architecture and fibrosis.

Imaging

Images of stained tissue sections were captured using a Leica DMI6000B motorized inverted microscope under brightfield illumination and a 10x objective. All imaging parameters, including exposure time, white balance, and focus, were standardized across samples to ensure consistency in image quality. Tile scans were stitched together using Leica Application Suite X (LAS X) software. Images were acquired through the University of Arizona Optical Imaging Core Facility (RRID:SCR_023355).

Image quantification

Images were analyzed in ImageJ to measure collagen area. The scale was set with distance = 0, known distance = 0, and pixel aspect ratio = 1.0. Images were converted to an RGB stack, and thresholds were adjusted in the blue channel to isolate blue and red pixels. Thresholds for blue pixels were set to 130–210 for control tissue and 180–210 for AFib tissue, while thresholds for red pixels were set to 0–100 for control tissue and 0–150, respectively. Collagen and Muscle area were quantified relative to total tissue area. Statistical analysis was performed in SigmaPlot using an unpaired t-test with a significance of P < 0.05.

Results

Several procedural challenges required iterative refinement to ensure reliable pacing and consistent arrhythmia induction. Surgical adaptations, including loose ligation to reduce bleeding, use of custom elongated sheaths, and a pull-back lead-delivery technique improved pacing stability, while multi-lead ECG confirmation ensured accurate lead positioning.

Outcomes assessment

Atrial fibrillation was successfully induced in 4 of 6 (67%) animals within 80.3 ± 22.3 days of initiating pacing with 3 animals going into persistent AFib and one animal going into paroxysmal Afib as demonstrated by electrocardiogram (Fig 4) and Kaplan-Meier curve (Fig 5). Complication rates, including spontaneous conversion to sinus rhythm and rapid ventricular response, were documented and addressed through protocol modifications. One animal spontaneously reverted to sinus rhythm, and one died from ventricular tachycardia related complications. Ventricular response rates during pacing varied widely among animals (100–180 bpm); one animal had dramatically elevated ventricular responses close to 200 bpm and was refractory to beta-adrenergic and calcium-channel blockade. Interestingly, the sinus rates during their normal activity varied from sinus bradycardia 40–50 bpm to sinus tachycardia to over 200 bpm. No thromboembolic events were observed even though the animals were not anti-coagulated.

Fig 4. Cardiac Monitoring by Electrocardiograms.

Fig 4

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Electrocardiogram strip extracted from implanted cardiac monitor displaying. Normal Sinus Rhythm, Paced Rhythm, and Atrial Fibrillation (AFib).

Fig 5. AFib Induction Time.

Fig 5

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Kaplan-Meier curve depicting the proportion of pigs remaining free from induced AFib over this observation period (n = 6). Four of six pigs (67%) successfully converted to AFib during the study period, with conversions occurring at 14-, 94-, 105-, and 108-days post-induction attempt. Two pigs (33%) did not develop AFib during the observation window. The stepped curve represents individual AFib induction events, with the y-axis showing the proportion of subjects not yet induced into AFib and the x-axis showing time in days.

Protocol adjustments

Protocol refinements minimized mortality and pacing-related complications over time. This included frequent monitoring of each animal’s rhythm during pacing. We did not initiate pacing until one week after pacer implantation to ensure that the atrial lead was securely fixed in the right atrial appendage wall. Once we initiated pacing, we would closely monitor each animal’s behavior to make sure that they were not suffering any side effects from the pacing. Occasionally pacing initiated hiccups because of intermittent diaphragmatic pacing, that was solved by decreasing the voltage on the unit. One animal went into ventricular tachycardia every time we initiated pacing. Upon necropsy, it was found that the atrial lead was implanted too close to the tricuspid valve and thus pacing the right ventricle as opposed to the right atrial appendage. The Yucatan model supported multi-week maintenance of persistent AFib, contrasting with traditional domestic pig models that often-required euthanasia after approximately 20 days due to heart-failure [4]. Comparable in chronicity to more recent Landrace tachypacing studies achieving ~6 weeks of AFib, this model offers the advantages of smaller, more robust animals and continuous rhythm monitoring, enabling extended-duration studies of persistent AFib [5].

Activity monitoring

Activity levels documented 24/7 with the FitBark activity trackers showed decreased activity with the occurrence of persistent AFib (Fig 6). To our knowledge this is the first report of documented decreases in activity in an animal model of AFib. This shows the clinical relevance of this model, i.e., being able to equate the presence of persistent AFib with a decrease in quality of life in an animal model.

Fig 6. AFib Activity Level.

Fig 6

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Hourly activity levels, tracked using Fitbark collars show a significant decrease during AFib episodes compared to baseline, mirroring human symptoms like fatigue and exercise intolerance. #P < 0.01, *P < 0.05 refers to persistent AFib versus baseline.

Histological evaluation

Masson’s trichrome staining revealed myocardial architecture differences in animals that were induced into persistent AFib. Overall, blue staining on Masson’s trichrome reflects collagen-rich extracellular matrix and fibrous connective tissue, including interstitial and perivascular extracellular matrix (ECM) components. Red staining on Masson’s trichrome highlights muscle fibers and cytoplasmic proteins, predominantly reflecting viable myocardium, including cardiomyocytes and smooth muscle cells. Our data display an increased fibrosis within the ECM and a significant reduction in cardiac muscle tissue (Fig 7). This pattern reflects loss of functional atrial muscle and expansion of collagen-rich ECM, a substrate that impairs atrial contractility, disrupts electrical conduction, and promotes AFib maintenance, thereby supporting the clinical relevance and translational fidelity of this large-animal model.

Fig 7. Histopathological Analysis of persistent AFib tissue. Masson’s trichrome staining of left and right atrial biopsies were imaged and analyzed for blue/red positive staining in ImageJ.

Fig 7

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Swine that were induced into persistent atrial fibrillation displayed increased collagen staining and significantly reduced muscle staining (P < 0.05) and (P < 0.001).

Discussion

This study introduces a technology-enhanced Yucatan miniswine model of persistent AFib that incorporates continuous rhythm and activity monitoring. The use of Medtronic Reveal LINQ™ implantable internal cardiac monitors provided uninterrupted ECG data, enabling precise characterization of AFib onset, duration, and ventricular response in freely moving animals. This approach overcomes limitations of prior large-animal AFib models, which often relied on intermittent surface ECGs or short-duration telemetry and consequently captured only limited snapshots of arrhythmia burden.

The addition of Fitbark 2 accelerometer collars supplied continuous, quantitative behavioral data without the need for handling or restraint. Previous AFib models have generally lacked objective assessments of spontaneous physical activity or functional changes during arrhythmia. In contrast, the combined monitoring approach used here produced a comprehensive dataset linking presence of persistent AFib with real-time activity patterns. Notably, animals demonstrated reduced activity during persistent AFib compared with their sinus-rhythm baseline, providing an objective indicator of functional change associated with the arrhythmia (Fig 6). This observation is consistent with well-established associations between AFib and reduced exercise capacity in clinical populations [6–7] and supports the relevance of activity measurements as a surrogate for quality of life and functional decline in preclinical studies.

The ability to track both electrical and behavioral parameters enhances the utility of this model for evaluating therapeutic interventions. Continuous activity monitoring offers a functional endpoint that complements rhythm analysis and permits assessment of whether an intervention affects both AFib burden and activity levels. This dual-parameter approach aligns with contemporary clinical evaluation of AFib therapies, which need to incorporate functional and quality of life metrics alongside rhythm outcomes.

Histological analyses

Persistent AFib in our model was associated with clear structural remodeling of the atrial myocardium. Quantitative analysis of Masson’s trichrome staining of left and right atrial biopsies demonstrated an increase in fibrosis with a corresponding significant reduction in atrial myocardial tissue, indicating replacement of functional myocardium by fibrotic scar (Fig 7). This pattern of enhanced fibrosis and myocyte loss is consistent with atrial cardiomyopathy observed in patients with longstanding AFib and supports that our swine model recapitulates the histopathological substrate that sustains and perpetuates persistent atrial fibrillation with high fidelity.

Comparison with prior AFib models

Earlier AFib models utilized domestic farm pigs, goats, and dogs [8]. Domestic swine breeds like Yorkshire or Landrace grow fast, complicating long-term studies. In contrast, Yucatan miniswine remains smaller, making extended follow-up and housing easier. Goats (~50–70 kg) were the first species used for chronic AFib, while canines, such as beagles, have been used for pacing-induced AFib. The Yucatan model balances human-like cardiac anatomy and a smaller, more manageable size, improving long-term study practicality and animal welfare, challenges domestic pig models struggled to overcome.

There is recent work on including transgenic or optogenetic AFib models. Importantly, this work has been done mice, rats, and in isolated atrial tissue, where investigators have developed new ways to study the mechanisms of AFib and potentially can be applied to study control electrical activity the role of rotors [9–10]. These approaches will potentially help develop new therapies based on these platforms, but they ultimately will have to be investigated in large animal models of persistent AFib. Our model provides an ideal prototype where investigators can define the precise onset of AFib, how long it lasts and its effects on clinical activity. Lastly, tissue from our model will provide gene and protein analyses in a clinically relevant model.

Our model induces AFib by chronic rapid atrial pacing of the right atrial appendage at ~400 beats per minute (bpm). This continuous atrial tachypacing approach is modeled after classic experiments in goats, dogs, and pigs, which demonstrate maintaining a high atrial rate for days to weeks can produce self-sustaining AFib through electrical remodeling. In a seminal goat study, AFib became sustained (> 24 hours) after about 7 days of continuous rapid atrial pacing in 10 of 11 goats [3]. Similarly, chronic right atrial pacing at 400 bpm for 6 weeks in a canine model created a substrate where AFib was easily inducible and maintained for a long duration [11].

Previous swine models used different pacing strategies with varying success. Early attempts at AFib in pigs often involved burst pacing, delivering short, high-frequency pulses in the right atrium to trigger fibrillation. While such bursts could initiate AFib episodes, they usually lasted only seconds to minutes before self-terminating. With sequential pacing and vagal stimulation (neostigmine) in an acute pig model could result in AFib, episodes lasted only ~3.6 minutes on average, with 78% spontaneously reverting to sinus rhythm [12]. Without prolonged pacing, standard domestic pigs struggled to maintain persistent AFib. A 2004 study achieved sustained AFib in pigs using extreme atrial burst pacing at 42 Hz (~2500 bpm) with an implanted pacemaker [4]. AFib became persistent after ~5 days but resulted in a rapid ventricular response (~274 bpm), leading to tachycardia-induced cardiomyopathy and heart failure within 2–3 weeks. Our previous work with other cardiac diseases in Yucatan miniswine shows how valuable this Yucatan model is for studying heart failure after myocardial infraction, developing immune modulation to treat heart failure and effects of lack of socialization on physical activity during COVID [13–16]. Additionally, our team has recently completed a comprehensive review of AFib animal models across both large and small animal species [17].

Limitations

Additional histological, echocardiographic, and magnetic resonance imaging (MRI) analyses could be investigated to further characterize atrial remodeling and fibrosis associated with this model. Importantly the pacing device and custom software used in this study are no longer available, which may affect direct replication of the stimulation protocol. Despite these constraints, the methods described here provide a robust and reproducible platform for studying AFib pathophysiology and assessing emerging therapeutic strategies in a large-animal model.

Data Availability

All relevant data are within the paper and its Supporting Information files. Data repository can be found at 10.25422/azu.data.30471077.

Funding Statement

This work was supported by Tech Launch Arizona Asset Development Grant UA17-095, the WARMER Research Foundation, and the Sarver Heart Center, University of Arizona.” “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Kamal Sharma

11 Jul 2025

Yucatan Mini Swine Model of Persistent Atrial Fibrillation: Clinical Relevance

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[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

?>

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the protocol been described in sufficient detail??>

To answer this question, please click the link to protocols.io in the Materials and Methods section of the manuscript (if a link has been provided) or consult the step-by-step protocol in the Supporting Information files.

Reviewer #1: Partly

Reviewer #2: Yes

**********

3. Does the protocol describe a validated method??>

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. If the manuscript contains new data, have the authors made this data fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the article presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: Yes

**********

Reviewer #1: Comments to the authors

This manuscript presents a new Yucatan mini swine model for sustained AFib which overcomes many of the limitations of previous large-animal models by capitalizing on the anatomical and physiological consistency of the Yucatan mini swine with that of humans. The major novelty of the study is that it uses implantable cardiac monitors (Medtronic Reveal LINQ™) and Fitbark 2.0 activity trackers to allow continuous monitoring of both arrhythmia and behavioral changes – a substantial translational value.

The Yucatan swine animal model is well-given, providing several advantages over other domestic breeds in regard to size consistency and potential long-term investigations. Furthermore, the fact that individual surgical approaches and device modifications, made more extensive operations or those with adverse anatomical conditions feasible, is indicative of good technical performance.

Together, the model provides a reliable and clinically applicable system for chronic AFib investigation and therapy assessment, potentially allowing us to better understand the arrhythmia-associated functional impact.

Major Weaknesses

1.The authors should report exact quantitative details and statistical analysis for their main results?

This manuscript does not yet adequately report statistics on the results (time to AFib induction, variability in ventricular rates, extent of activity reduction) and histological changes observed in trial animals (e.g. fibrosis).

I also invite them to add a more complete statistical analysis and the corresponding graphical summaries (e.g., time to AFib induction as well as activity and rate variability, in the form of Kaplan-Meier curves and bar plots with error bars, respectively) to ensure the clarity and strength of your findings.

2.I'd suggest: They could validate their model more thoroughly on the molecular and histopathological level:

The present manuscript yields little evidence for atrial remodeling, fibrosis or gene expression changes which are necessary to support the translational relevance of model to human AFib.

Integration of echocardiographic and histological analysis, and molecular markers of structural and electrophysiological remodeling, will reveal the pathophysiological relationships between the model and clinical AFib.

3.Proper discussion of limitations of the model in the discussion section?

The manuscript is too focused on strengths of the model without enough discussion of limitations such as: variable ventricular rates, n=6, early death of one animal, and its lack of relevance to other types of AF such as paroxysmal AF.

I suggest a fair and honest account on these challenges and their implications on the robustness and clinical relevance of the model. This makes your results more reliable and easier to interpret.

4.Critically compare the model to the more recent literature of large-animal AFib research?

Although major historical models are mentioned, the manuscript does not provide an in-depth comparison with the more recent and emerging, including transgenic or optogenetic AFib models.

Would like to see more of comparative analysis between your model and current large animal models and incorporate knowledge of modern techniques. This should help place your work more effectively in the changing AFib research environment.

Minor Points for Revision

•Grammar and Style: Clarify sentences and eliminate slangy language (e.g., "pigs presumably feel better").

•Figures: 1) Other than captions figure quality and resolution is needed (e.g., Figure 3 needs statistics and clearly labeled axes).

•Data Availability: raw ECG and summary data should be made available to the research community in an appropriate format.

Reviewer #2: This paper compares previous AFib models with swine and focusing on key methodological differences as well as outcomes. The manuscript is organized nicely. Following comment would strengthen manuscript.

Comment 1: In the result section

•It is not clear in terms of clarity and conciseness, e.g. Persistent AFib was induced in ⅚ subjects within 60 days. It should be 5/6 along with %

•In addition, reorganization contents would help.

•It is unclear about cited reference “Pharmacologic intervention with beta-blockers and calcium channel blockers did not control rapid ventricular rates in one subject (Bishop & Akram, 2021; Pratt et al., 1983)”

•A separate Protocol adjustments section is highly recommended along with reason of amendment.

•A tabular comparison which includes animal model, clinical limitation and clinical relevance would add more weightage.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: Yes:  Prakash Sojitra, PhD

**********

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PLoS One. 2026 Feb 4;21(2):e0340985. doi: 10.1371/journal.pone.0340985.r002

Author response to Decision Letter 1

16 Dec 2025

We thank the reviewers for their repsonses. We have a more detailed response to the reviewers attached for ease. Please let us know if you need anything. Thank you very much!

Attachment

Submitted filename: Pouria Response to Reviewers Final 12-16-2025 + Header.docx

pone.0340985.s003.docx (1,009.2KB, docx)

Decision Letter 1

Kamal Sharma

30 Dec 2025

Yucatan Mini Swine Model of Atrial Fibrillation: Clinical Relevance

PONE-D-25-22478R1

Dear Dr. Goldman,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Kamal Sharma

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

?>

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the protocol been described in sufficient detail??>

To answer this question, please click the link to protocols.io in the Materials and Methods section of the manuscript (if a link has been provided) or consult the step-by-step protocol in the Supporting Information files.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Does the protocol describe a validated method??>

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. If the manuscript contains new data, have the authors made this data fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the article presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: Yes

**********

Reviewer #1: The manuscript presents a well-designed and clinically relevant large-animal protocol for inducing persistent atrial fibrillation, addressing key limitations of existing AF models. The use of Yucatan miniswine, chronic atrial pacing, continuous rhythm monitoring, and functional activity tracking represents a significant methodological strength with high translational value. The protocol is described in sufficient technical detail to enable reproducibility by other laboratories, which is a major asset for a methods-focused publication. Validation of persistent AF, survival outcomes, and histological confirmation of atrial remodeling adequately support the robustness of the model. Although the sample size is limited, this is acceptable for a protocol development study and is transparently acknowledged. Overall, this work constitutes a valuable methodological contribution to the field and will be of interest to researchers developing and testing therapies for atrial fibrillation.

Reviewer #2: Revised manuscript is now edited appropriately and justifications cited in cover letter are sufficient.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #1: No

Reviewer #2: Yes:  Prakash Sojitra, PhD

**********

Attachment

Submitted filename: Reviewer Attachement.docx

pone.0340985.s002.docx (11.9KB, docx)

Acceptance letter

Kamal Sharma

PONE-D-25-22478R1

PLOS One

Dear Dr. Goldman,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

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If we can help with anything else, please email us at customercare@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Kamal Sharma

Academic Editor

PLOS One

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: Pouria Response to Reviewers Final 12-16-2025 + Header.docx

    pone.0340985.s003.docx (1,009.2KB, docx)
    Attachment

    Submitted filename: Reviewer Attachement.docx

    pone.0340985.s002.docx (11.9KB, docx)

    Data Availability Statement

    All relevant data are within the paper and its Supporting Information files. Data repository can be found at 10.25422/azu.data.30471077.

    Articles from PLOS One are provided here courtesy of PLOS

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