Temperature and repeated catecholamine surges modulate regional wall motion abnormalities in a rodent takotsubo syndrome model

Abstract Transient regional wall motion abnormalities (RWMA) after stress are a hallmark of experimental and clinical Takotsubo Syndrome (TS). The mechanisms driving RWMA remain incompletely understood. This study investigates these mechanisms in a small-animal model of TS, validating the model’s co...

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Main Authors: Ermir Zulfaj, AmirAli Nejat, Abdulhussain Haamid, Aaron Espinosa, Ahmed Elmahdy, Tetiana Pylova, Sandeep Jha, Björn Redfors, Elmir Omerovic
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-88410-9
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author Ermir Zulfaj
AmirAli Nejat
Abdulhussain Haamid
Aaron Espinosa
Ahmed Elmahdy
Tetiana Pylova
Sandeep Jha
Björn Redfors
Elmir Omerovic
author_facet Ermir Zulfaj
AmirAli Nejat
Abdulhussain Haamid
Aaron Espinosa
Ahmed Elmahdy
Tetiana Pylova
Sandeep Jha
Björn Redfors
Elmir Omerovic
author_sort Ermir Zulfaj
collection DOAJ
description Abstract Transient regional wall motion abnormalities (RWMA) after stress are a hallmark of experimental and clinical Takotsubo Syndrome (TS). The mechanisms driving RWMA remain incompletely understood. This study investigates these mechanisms in a small-animal model of TS, validating the model’s complication profile, recovery dynamics, and recurrence, while assessing the predictive value of echocardiography. Male, 7-9-week-old rats underwent TS induction via isoprenaline infusion. The effects of body temperature and repeated catecholaminergic surges on RWMA were assessed using high-resolution speckle-tracking echocardiography. Complications were evaluated through ECG, autopsy, and blood gas analysis. The TS phenotype showed reduced longitudinal strain with RWMA characterized by apical end-systolic akinesia/dyskinesia, a contracting base, and a narrow transition zone, resulting in apical ballooning. RWMA originated from the apex and recovered in the opposite direction. Hyperthermia increased RWMA incidence, while hypothermia attenuated RWMA (p = 0.008). A repeated catecholamine surge exacerbated RWMA in the acute phase (p = 0.042) but not during recovery (p = 0.308), with reduced RWMA susceptibility after recovery (RR 0.45, 95%CI; 0.27–0.76). Systolic function at initial echocardiography predicted worse outcomes (odds ratio 0.73; 95%CI 0.57–0.85), and RWMA extent correlated with recovery time (Rho = 0.772). TS rats developed complications similar to patients, including heart failure, arrhythmias, and thrombus formation. This study validates the small-animal TS model by replicating patient findings, and emphasizing the importance of controlling body temperature and limiting adrenergic drug use in managing TS. RWMA analysis offers promise as a diagnostic and prognostic tool in TS, and the delayed adaptive response presents a potential pathway for therapeutic intervention.
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spelling doaj-art-47635d51aee94944ab2a676b6c94c8922025-02-02T12:24:31ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-88410-9Temperature and repeated catecholamine surges modulate regional wall motion abnormalities in a rodent takotsubo syndrome modelErmir Zulfaj0AmirAli Nejat1Abdulhussain Haamid2Aaron Espinosa3Ahmed Elmahdy4Tetiana Pylova5Sandeep Jha6Björn Redfors7Elmir Omerovic8Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at Gothenburg UniversityDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at Gothenburg UniversityCore Facilities - Experimental Biomedicine, Sahlgrenska AcademyDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at Gothenburg UniversityDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at Gothenburg UniversityDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at Gothenburg UniversityDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at Gothenburg UniversityDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at Gothenburg UniversityDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at Gothenburg UniversityAbstract Transient regional wall motion abnormalities (RWMA) after stress are a hallmark of experimental and clinical Takotsubo Syndrome (TS). The mechanisms driving RWMA remain incompletely understood. This study investigates these mechanisms in a small-animal model of TS, validating the model’s complication profile, recovery dynamics, and recurrence, while assessing the predictive value of echocardiography. Male, 7-9-week-old rats underwent TS induction via isoprenaline infusion. The effects of body temperature and repeated catecholaminergic surges on RWMA were assessed using high-resolution speckle-tracking echocardiography. Complications were evaluated through ECG, autopsy, and blood gas analysis. The TS phenotype showed reduced longitudinal strain with RWMA characterized by apical end-systolic akinesia/dyskinesia, a contracting base, and a narrow transition zone, resulting in apical ballooning. RWMA originated from the apex and recovered in the opposite direction. Hyperthermia increased RWMA incidence, while hypothermia attenuated RWMA (p = 0.008). A repeated catecholamine surge exacerbated RWMA in the acute phase (p = 0.042) but not during recovery (p = 0.308), with reduced RWMA susceptibility after recovery (RR 0.45, 95%CI; 0.27–0.76). Systolic function at initial echocardiography predicted worse outcomes (odds ratio 0.73; 95%CI 0.57–0.85), and RWMA extent correlated with recovery time (Rho = 0.772). TS rats developed complications similar to patients, including heart failure, arrhythmias, and thrombus formation. This study validates the small-animal TS model by replicating patient findings, and emphasizing the importance of controlling body temperature and limiting adrenergic drug use in managing TS. RWMA analysis offers promise as a diagnostic and prognostic tool in TS, and the delayed adaptive response presents a potential pathway for therapeutic intervention.https://doi.org/10.1038/s41598-025-88410-9Takotsubo SyndromeRegional Wall Motion abnormalitiesRat modelBody temperatureEchocardiographyComplication
spellingShingle Ermir Zulfaj
AmirAli Nejat
Abdulhussain Haamid
Aaron Espinosa
Ahmed Elmahdy
Tetiana Pylova
Sandeep Jha
Björn Redfors
Elmir Omerovic
Temperature and repeated catecholamine surges modulate regional wall motion abnormalities in a rodent takotsubo syndrome model
Scientific Reports
Takotsubo Syndrome
Regional Wall Motion abnormalities
Rat model
Body temperature
Echocardiography
Complication
title Temperature and repeated catecholamine surges modulate regional wall motion abnormalities in a rodent takotsubo syndrome model
title_full Temperature and repeated catecholamine surges modulate regional wall motion abnormalities in a rodent takotsubo syndrome model
title_fullStr Temperature and repeated catecholamine surges modulate regional wall motion abnormalities in a rodent takotsubo syndrome model
title_full_unstemmed Temperature and repeated catecholamine surges modulate regional wall motion abnormalities in a rodent takotsubo syndrome model
title_short Temperature and repeated catecholamine surges modulate regional wall motion abnormalities in a rodent takotsubo syndrome model
title_sort temperature and repeated catecholamine surges modulate regional wall motion abnormalities in a rodent takotsubo syndrome model
topic Takotsubo Syndrome
Regional Wall Motion abnormalities
Rat model
Body temperature
Echocardiography
Complication
url https://doi.org/10.1038/s41598-025-88410-9
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