Hyperthermia as a trigger for Takotsubo syndrome in a rat model

Figures

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  Figure 1. Experimental schematic of hyperthermic experiments with and without cooling to 150 min post-isoprenaline administration.

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  Figure 2. High-dose isoproterenol (50 mg.kg−1) under euthermic conditions does not result in TTS-like contractility. (A) 50 mg.kg−1 isoprenaline under ketamine-midazolam anesthesia resulted in a significant positive inotropic response in both apical and basal myocardial segments, although not for all time-points in the apex. No significant difference was seen between apical and basal contractility (n = 8). *P < 0.05, **P < 0.01, ***P < 0.001 vs. baseline (apex); ###P < 0.001 vs. baseline (base) two-way repeated measures ANOVA. (B) Rectal temperature increases after isoproterenol, although this is attenuated by removing heating from the animal. *P < 0.05, **P < 0.01, ***P < 0.001 relative to time 0, one-way ANOVA (n = 8 animals).

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  Figure 3. High-dose isoproterenol (50 mg.kg−1) administration under hyperthermic conditions (~41°C) results in apical-hypocontractility. (A) 50 mg.kg−1 isoprenaline under ketamine-midazolam anesthesia resulted a significant positive inotropic response was seen in the basal myocardial segment for the first 60 min, whereas the apical myocardial segment showed a significant negative inotropic response at 80 and 90 min post-isoprenaline. **P < 0.01 apex vs. baseline; $P < 0.05 apex vs. base; #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001 base vs. baseline, two-way repeated measures ANOVA (n = 6). (B) Sustained heating of the animal maintains a significant elevated body temperature post-isoproterenol. *P < 0.05, **P < 0.01, ***P < 0.001 relative to baseline temperature, one-way ANOVA (n = 6 animals).

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  Figure 4. Rapid cooling of animals after the induction of apical dysfunction did not reverse or attenuate the hypocontractility. (A) Rapid changes in body temperature could be achieved through the application of cooling. (B) No effect of cooling was observed on apical dysfunction on rats cooled at 60 min (from orange dotted line) or 90 min (from green dotted line); n = 6 animals per group. Repeated measures ANOVA.

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  Figure 5. In vitro hyperthermia had no significant effect on either baseline contractility at 10 or 20 min post-temperature change (A) or the increase in contractility when 10−6 M isoproterenol was applied at either 10 or 20 min post-isoproterenol (B). One-way ANOVA, n = 9 and 10 cells (A), 8 and 7 (B), 37 and 41°C, respectively.

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  Figure 6. Representative parasternal long axis B-mode images of end-diastole (top) and end-systole (bottom) after induction of TTS-like contractility (base: left; apex: right), with trace (red line) drawn around endocardial border. Scale in mm.