Hyperthermia as a trigger for Takotsubo syndrome in a rat model

Tranter, Matthew H.; Redfors, Björn; Couch, Liam S.; Lyon, Alexander R.; Ömerovic, Elmir; Harding, Siân E.

doi:10.3389/fcvm.2022.869585

Cited by 4 publications

(6 citation statements)

References 43 publications

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“…This addresses the limitation of uncontrolled drug levels in the bloodstream associated with IP injections. Additionally, hyperthermic conditions ( 23 ) are unnecessary in this model, and it accurately replicates key TS features across sexes ( 86 ). The onset is acute, peaking at 4–6 h, followed by a recovery phase at 24 h. Rats recover in cardiac function and contractility within 1–14 days, with the majority recovering within 48–72 h. At 30 days, all surviving rats show normal behaviour, ECG, and imaging.…”

Section: Animal Models Of Takotsubo Syndromementioning

confidence: 97%

“…Not everyone develops TS following a stressful event, suggesting that a variety of factors influence its development. Some reported factors are related to thyroid function ( 21 ), climatic and body temperatures ( 22 , 23 ), malignancy ( 24 ), as well as age, sex, and neurological and psychiatric disorders.…”

Section: Clinical Characteristics Of Takotsubo Syndromementioning

confidence: 99%

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Animal models of Takotsubo syndrome: bridging the gap to the human condition

Zulfaj,

Nejat,

Haamid

et al. 2024

Front. Cardiovasc. Med.

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Modelling human diseases serves as a crucial tool to unveil underlying mechanisms and pathophysiology. Takotsubo syndrome (TS), an acute form of heart failure resembling myocardial infarction, manifests with reversible regional wall motion abnormalities (RWMA) of the ventricles. Despite its mortality and clinical similarity to myocardial infarction, TS aetiology remains elusive, with stress and catecholamines playing central roles. This review delves into current animal models of TS, aiming to assess their ability to replicate key clinical traits and identifying limitations. An in-depth evaluation of published animal models reveals a variation in the definition of TS among studies. We notice a substantial prevalence of catecholamine-induced models, particularly in rodents. While these models shed light on TS, there remains potential for refinement. Translational success in TS research hinges on models that align with human TS features and exhibit the key features, including transient RWMA. Animal models should be comprehensively evaluated regarding the various systemic changes of the applied trigger(s) for a proper interpretation. This review acts as a guide for researchers, advocating for stringent TS model standards and enhancing translational validity.

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Section: Animal Models Of Takotsubo Syndromementioning

confidence: 97%

Section: Clinical Characteristics Of Takotsubo Syndromementioning

confidence: 99%

Animal models of Takotsubo syndrome: bridging the gap to the human condition

Zulfaj,

Nejat,

Haamid

et al. 2024

Front. Cardiovasc. Med.

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“…This hypothesis is supported by an in silico modelling study that recreated Takotsubo-like contractile dysfunction with apical dysfunction following intense agonist stimulation when apical-basal β 1 AR and β 2 AR gradients were introduced [ 41 ]. Further, TTS-like dysfunction can be induced in vivo by bolus injection adrenaline or isoprenaline [ 20 , 21 , 42 , 43 , 44 ]. Interestingly, the hyperthermic response subsequent to catecholamine administration seems necessary for the induction of TTS, since a recent in vivo study demonstrated that maintenance of hyperthermia would induce TTS-like contractile dysfunction following isoprenaline administration, whereas active cooling prevented, but did not reverse, these changes [ 43 ].…”

Section: Cardiomyocyte Contractility and The Adrenergic Systemmentioning

confidence: 99%

“…Further, TTS-like dysfunction can be induced in vivo by bolus injection adrenaline or isoprenaline [ 20 , 21 , 42 , 43 , 44 ]. Interestingly, the hyperthermic response subsequent to catecholamine administration seems necessary for the induction of TTS, since a recent in vivo study demonstrated that maintenance of hyperthermia would induce TTS-like contractile dysfunction following isoprenaline administration, whereas active cooling prevented, but did not reverse, these changes [ 43 ].…”

Section: Cardiomyocyte Contractility and The Adrenergic Systemmentioning

confidence: 99%

Molecular Mechanisms of Takotsubo Syndrome

Couch

Channon²,

Thum³

2022

IJMS

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Takotsubo syndrome (TTS) is a severe but reversible acute heart failure syndrome that occurs following high catecholaminergic stress. TTS patients are similar to those with acute coronary syndrome, with chest pain, dyspnoea and ST segment changes on electrocardiogram, but are characterised by apical akinesia of the left ventricle, with basal hyperkinesia in the absence of culprit coronary artery stenosis. The pathophysiology of TTS is not completely understood and there is a paucity of evidence to guide treatment. The mechanisms of TTS are thought to involve catecholaminergic myocardial stunning, microvascular dysfunction, increased inflammation and changes in cardiomyocyte metabolism. Here, we summarise the available literature to focus on the molecular basis for the pathophysiology of TTS to advance the understanding of the condition.

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“…Hyperthermia has been recently suggested as a possible trigger for TTS, via a rise in body temperature due to a catecholamine storm ( 88 ). We propose that orexin influences this cascade, as emerging evidence suggests it plays a role in thermoregulation ( 89 ) and in regulating the HPT-axis ( 20 ).…”

Section: Alternative Explanatory Framework For Pathophysiology Of Tts...mentioning

confidence: 99%

Orexin/hypocretin system dysfunction in patients with Takotsubo syndrome: A novel pathophysiological explanation

Knez

Nikšić

Ömerovic

2022

Front. Cardiovasc. Med.

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Takotsubo syndrome (TTS) is an acute heart failure syndrome. Emotional or physical stressors are believed to precipitate TTS, while the pathophysiological mechanism is not yet completely understood. During the coronavirus disease (COVID-19) pandemic, an increased incidence of TTS has been reported in some countries; however, the precise pathophysiological mechanism for developing TTS with acute COVID-19 infection is unknown. Nevertheless, observing the symptoms of COVID-19 might lead to new perspectives in understanding TTS pathophysiology, as some of the symptoms of the COVID-19 infection could be assessed in the context of an orexin/hypocretin-system dysfunction. Orexin/hypocretin is a cardiorespiratory neuromodulator that acts on two orexin receptors widely distributed in the brain and peripheral tissues. In COVID-19 patients, autoantibodies against one of these orexin receptors have been reported. Orexin-system dysfunction affects a variety of systems in an organism. Here, we review the influence of orexin-system dysfunction on the cardiovascular system to propose its connection with TTS. We propose that orexin-system dysfunction is a potential novel explanation for the pathophysiology of TTS due to direct or indirect dynamics of orexin signaling, which could influence cardiac contractility. This is in line with the conceptualization of TTS as a cardiovascular syndrome rather than merely a cardiac abnormality or cardiomyopathy. To the best of our knowledge, this is the first publication to present a plausible connection between TTS and orexin-system dysfunction. We hope that this novel hypothesis will inspire comprehensive studies regarding orexin's role in TTS pathophysiology. Furthermore, confirmation of this plausible pathophysiological mechanism could contribute to the development of orexin-based therapeutics in the treatment and prevention of TTS.

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Hyperthermia as a trigger for Takotsubo syndrome in a rat model

Cited by 4 publications

References 43 publications

Animal models of Takotsubo syndrome: bridging the gap to the human condition

Animal models of Takotsubo syndrome: bridging the gap to the human condition

Molecular Mechanisms of Takotsubo Syndrome

Orexin/hypocretin system dysfunction in patients with Takotsubo syndrome: A novel pathophysiological explanation

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