Takotsubo syndrome-like model in rats with high reproducibility and low mortality

Abstract Background/Purpose Takotsubo syndrome (TS) is an acute form of heart failure with similar mortality and clinical presentation as myocardial infarction. The pathophysiology the potentially life-threatening only partially understood. This experimental study aimed to produce a human-like TS model high reproducibility low mortality. Rats have been small-animal choice for preclinical studies within cardiovascular field, successfully translating gained knowledge humans. A relevant animal can aid in elucidating mechanisms behind serve platform developing evidence-based treatment guidelines specific disease, which are currently missing. Methods 190 Sprague Dawley rats (male, ∼300 g, ∼47 d) were infused i.v. single dose β-adrenergic agonist isoprenaline. first group was randomized by infusion time (ranging from 1 min 60 min) while maintaining fixed total (6.25 mg/kg), second (0.1–50 mg/kg) specified time. replicated saline control. looked at mortality, incidence apical akinesia, extent recovery ECG, HR, SpO2, temperature monitored during induction phase (<60 points imaging. High-resolution speckle-tracking echocardiography used function up 30 days. followed principles laboratory care approved our institution's Animal Ethics Committee. Results Mechanical dyssynchrony preceded global contractile dysfunction development transient akinesia. LV contractility normalised after 7 All surviving showed normal behaviour, imaging TS-like phenotype achieved 92.9% survivors. Mortality 30-day 6.7%. deceased animals developed complications like patients including failure, malignant arrhythmias, mural thrombus formation, cardiogenic shock. Longer associated increased (p=0.002), but not akinesia (p=0.818). decreased shortest (1 7.5 minutes above, it did differ. replication validated these findings, although variability seen across groups. Conclusions provides highly reproducible excellent translational potential. natural course demonstrated presence most critical characteristics also validates other findings related susceptibility develop complications. Our solid future TS. Funding Acknowledgement Type funding sources: Public grant(s) – National budget only. Main source(s): ALF - Swedish Research Council