Early treatment with isoflurane attenuates left ventricular dysfunction and improves survival in experimental Takotsubo

Oras, Jonatan; Redfors, Björn; Ali, Anwar; Alkhoury, Jessica; Seeman-Lodding, H.; Ömerovic, Elmir; Ricksten, Sven‐Erik

doi:10.1111/aas.12861

Cited by 8 publications

(6 citation statements)

References 27 publications

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“…Early treatment with isoflurane reduced left ventricular dyskinesia and improved the survival rate of experimental TTS, while H 2 S reduced ROS formation by reducing NADPH oxidase [202,203]. GPER, azelnidipine, Tempol and amlodipine also played a protective role for TTS [153,186,204,205].…”

Section: Animal Models and Mechanistic Studiesmentioning

confidence: 95%

Takotsubo Syndrome: Translational Implications and Pathomechanisms

Fan

Yang

Kowitz

et al. 2022

IJMS

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Takotsubo syndrome (TTS) is identified as an acute severe ventricular systolic dysfunction, which is usually characterized by reversible and transient akinesia of walls of the ventricle in the absence of a significant obstructive coronary artery disease (CAD). Patients present with chest pain, ST-segment elevation or ischemia signs on ECG and increased troponin, similar to myocardial infarction. Currently, the known mechanisms associated with the development of TTS include elevated levels of circulating plasma catecholamines and their metabolites, coronary microvascular dysfunction, sympathetic hyperexcitability, inflammation, estrogen deficiency, spasm of the epicardial coronary vessels, genetic predisposition and thyroidal dysfunction. However, the real etiologic link remains unclear and seems to be multifactorial. Currently, the elusive pathogenesis of TTS and the lack of optimal treatment leads to the necessity of the application of experimental models or platforms for studying TTS. Excessive catecholamines can cause weakened ventricular wall motion at the apex and increased basal motion due to the apicobasal adrenoceptor gradient. The use of beta-blockers does not seem to impact the outcome of TTS patients, suggesting that signaling other than the beta-adrenoceptor-associated pathway is also involved and that the pathogenesis may be more complex than it was expected. Herein, we review the pathophysiological mechanisms related to TTS; preclinical TTS models and platforms such as animal models, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) models and their usefulness for TTS studies, including exploring and improving the understanding of the pathomechanism of the disease. This might be helpful to provide novel insights on the exact pathophysiological mechanisms and may offer more information for experimental and clinical research on TTS.

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Section: Animal Models and Mechanistic Studiesmentioning

confidence: 95%

Takotsubo Syndrome: Translational Implications and Pathomechanisms

Fan

Yang

Kowitz

et al. 2022

IJMS

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“…Since experiments in a TTS rodent model with catecholamine-triggered TTS revealed that isoflurane anesthesia exerted a protective effect for development of LV dysfunction [ 126 , 127 ], it would be of great interest to evaluate even in a limited cohort this therapy’s impact in human TTS.…”

Section: Future Therapeutic Options For Ttsmentioning

confidence: 99%

Takotsubo Cardiomyopathy: Current Treatment

Madias

2021

JCM

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Management of takotsubo syndrome (TTS) is currently empirical and supportive, via extrapolation of therapeutic principles worked out for other cardiovascular pathologies. Although it has been emphasized that such non-specific therapies for TTS are consequent to its still elusive pathophysiology, one wonders whether it does not necessarily follow that the absence of knowledge of TTS’ pathophysiological underpinnings should prevent us for searching, designing, or even finding, therapies efficacious for its management. Additionally, it is conceivable that therapy for TTS may be in response to pathophysiological/pathoanatomic/pathohistological consequences (e.g., “myocardial stunning/reperfusion injury”), common to both TTS and coronary artery disease, or other cardiovascular disorders). The present review outlines the whole range of management principles of TTS during its acute phase and at follow-up, including considerations pertaining to the recurrence of TTS, and commences with the idea that occasionally management of TTS should consist of mere observation along the “first do no harm” principle, while self-healing is under way. Finally, some new therapeutic hypotheses (i.e., large doses of insulin infusions in association with the employment of intravenous short- and ultrashort-acting β-blockers) are being entertained, based on previous extensive animal work and limited application in patients with neurogenic cardiomyopathy and TTS.

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“…), isoflurane (an anaesthetic agent) was recently found to be effective both in the prevention and attenuation of TTC-induced LV dysfunction in experimental studies. 58,59 However, further studies are still warranted to discover novel agents with preventive features and disease-specific actions (targeted therapy) in the setting of TTC. Unfortunately, there exists no specific targeted therapy for the management of acute and/or residual LV dysfunction in the setting of TTC, and the use of supportive measures is generally indicated as the…”

Section: Management Of Left Ventricular Dysfunctionmentioning

confidence: 99%

Left Ventricular Dysfunction in the Setting of Takotsubo Cardiomyopathy: A Review of Clinical Patterns and Practical Implications

Yalta¹,

Yılmaztepe²,

Zorkun³

2018

Cardiac Failure Review

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Takotsubo cardiomyopathy (TTC) is primarily regarded as a form of acute and transient myocardial disease with a variety of characteristic wall-motion abnormalities. Importantly, a significant portion of TTC cases generally present with variable degrees of acute left ventricular (LV) dysfunction with or without clinical HF. On the other hand, LV dysfunction in the setting of TTC has been universally and exclusively considered as a synonym for systolic dysfunction, potentially overlooking other forms of myocardial pathologies, including transient diastolic dysfunction, in this setting. More interestingly, recent observations suggest that TTC, despite its macroscopic recovery, may not always manifest as a fully reversible phenomenon, suggesting persistence of microscopic changes at the cellular level to some degree. In clinical practice, these residual changes might largely account for the evolution of certain pathologies, including persistent diastolic dysfunction and subclinical LV dysfunction with variable symptomatology (particularly those arising during high levels of myocardial workload, including exercise, etc.) among TTC survivors. Within this context, the present review aims to highlight various clinical patterns and implications of LV dysfunction in the setting of TTC, and to provide basic information regarding morphological and mechanistic characteristics of wall-motion abnormalities in this setting.

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Early treatment with isoflurane attenuates left ventricular dysfunction and improves survival in experimental Takotsubo

Abstract: Early treatment with isoflurane attenuates the LV akinesia and improves survival in experimental TS. Isoflurane sedation in patients at risk of developing Takotsubo syndrome could be a subject for future studies.

Cited by 8 publications

References 27 publications

Takotsubo Syndrome: Translational Implications and Pathomechanisms

Takotsubo Syndrome: Translational Implications and Pathomechanisms

Takotsubo Cardiomyopathy: Current Treatment

Left Ventricular Dysfunction in the Setting of Takotsubo Cardiomyopathy: A Review of Clinical Patterns and Practical Implications

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