Echocardiographic characterization and functional impairment in an ex-vivo perfused rat model of takotsubo syndrome

Abstract Background Takotsubo Syndrome (TTS) is an acute transient form of heart failure with A hallmark echocardiographic feature of TTS is regional wall motion abnormalities. While substantial research has been conducted to unravel its pathophysiology, the underlying mechanisms of myocardial functional impairment in TTS remain poorly understood. Aim This study aims to investigate the effects of ex vivo-induced TTS in a rat model, focusing on key echocardiographic parameters to assess the extent of myocardial dysfunction Methods Twelve male Sprague-Dawley rats (~47 days old, ~300 g) were divided into two groups: ex vivo TTS and control. Isolated hearts were assessed for viability based on predefined inclusion criteria (Rate Pressure Product (RPP) 26,000, dp/dt ±2000, heart rate 200–500 bpm). Following stabilization, the ex vivo TTS group underwent TTS induction via a 15-minute isoprenaline infusion (1 mg/kg) using the Langendorff apparatus. Physiological parameters, including HR, SBP, DP, DPDT min, DPDT max, LVDP, RPP, TEMP, PO₂, and PCO₂, were continuously monitored for six hours. Ex vivo echocardiography (Vevo 3100, VISUALSONICS) was performed at multiple time points to evaluate myocardial changes, confirm the TTS phenotype, and assess regional wall motion abnormalities. Echocardiographic measurements, strain analysis, and speckle tracking were analyzed using Fujifilm Visual Sonics software. Results Successful TTS induction was confirmed through ex vivo echocardiography. Continuous monitoring of key cardiac function parameters, along with the detection of regional wall motion abnormalities, further supported this diagnosis. Strain analysis revealed pronounced regional wall motion abnormalities predominantly in the apical regions, accompanied by notable changes in cardiac function (figure 1). The ex vivo TTS group demonstrated a marked decrease in EF (p 0.0001) and GLS (p 0.0001), along with an increase in LVAI (p = 0.001), indicating severe myocardial dysfunction (figure 2).Substantial functional impairment in the ex vivo TTS group (Cohen’s d effect) and a strong negative correlation between EF and GLS (rho = -0.88), emphasizes the relationship between myocardial deformation and overall functional capacity. Conclusions By successfully establishing an ex vivo echocardiography protocol, our findings highlight the profound myocardial dysfunction associated with TTS. Significant reductions in EF and GLS, along with increased LVAI in the ex vivo TTS group, align with previously reported in vivo results. The strong correlation between myocardial dysfunction and impaired myocardial deformation underscores the severity of TTS. Moreover, ex vivo echocardiography illustrates the progressive nature of this disease model. These findings provide valuable insights into the pathophysiology of TTS and offer a robust platform for developing future therapeutic strategies aimed at myocardial recovery and functional preservation in TTS.Figure 1 figure 2