Abstract P1055: Takotsubo Syndrome Model In Rats

Abstract

Background: Takotsubo syndrome (TS) is an acute form of heart failure. The pathophysiology of the life-threatening syndrome is partially understood. A relevant animal model can aid in elucidating mechanisms behind TS. Current models of TS lack proper reproducibility, have high mortality, and fail to reflect the human condition adequately. This experimental study aimed to produce a human-like TS model. Methods: Rats were infused i.v. with a single dose of isoprenaline in varying doses (0.1-50 mg/kg) and infusion times (1-60 min). High-resolution speckle-tracking echo and 3D imaging was used to study heart function for up to 30 days. Results: Mechanical dyssynchrony preceded global contractile dysfunction and development of transient apical akinesia. Surviving rats showed normal behaviour, ECG and imaging at day 30. TS-like phenotype was achieved in 92.9% of survivors. Mortality at 30-day was 6.7%. The deceased animals developed complications like TS patients including heart failure, malignant arrhythmias, mural thrombus formation, cardiogenic shock. A dose-dependent relationship in incidence (p<0.0001), extent of akinesia (p<0.01), mortality (p<0.01), and cardiac function was seen with stress hormone. Systolic cardiac function at first echo was a good predictor for mortality (Odds Ratio 0.73; 95% CI 0.57-0.85), while the extent of akinesia strongly correlated with time until recovery (Rho = 0.86). Conclusions: This study provides a highly reproducible TS model with low mortality and excellent translational potential. High-resolution imaging and the natural course demonstrate the presence of the most critical characteristics of TS-like phenotype as in humans.