The importance of body temperature for the development of experimental Takotsubo

Introduction: Takotsubo cardiomyopathy (TCM), also known as stress-induced cardiomyopathy (SIC), is characterized by an acute onset of a reversible left ventricular akinesia that cannot be explained by an occlusion of a coronary artery. The mechanisms behind the pathogenesis of TCM are unknown but catecholamines are suggested to be involved. One theory is that excess metabolic demand may play a role. Cardiac metabolic demand is determined in part by body temperature, which is increased by catecholamines. Aims: To study the effect of body temperature on catecholamine-induced takotsubo cardiomyopathy and hemodynamics in rats. Methods: 76 male Sprague Dawley rats were anaesthetized by an intraperitoneal (i.p) administration of ketamine (50 mg/kg) and midazolam (5 mg/kg). They were placed on a heating pad and rectal temperature was continuously monitored. I.p isoprenaline (50 mg/kg) was administrated and the body temperature was controlled according to the experimental protocol. In the first experimental setup, the body temperature was allowed to increase spontaneously post isoprenaline (n=44). In the second set of experiments, 32 rats were randomized to temperature control post isoprenaline at 37.5 ± 0.5°C (normothermia, n=16) or 41.0 ± 0.5°C (hyperthermia, n=16). Invasive hemodynamics were measured in a subgroup of rats that had been randomized to normothermia (n=8) or hyperthermia (n=8). Left ventricular (LV) function was studied by echocardiography 90 minutes post isoprenaline administration. TCM-like akinesia was expressed as percentage of total LV endocardial length. Results: Peak body temperature was associated with the extent of isoprenaline-induced TCMlike dysfunction (r2=0.19, p=0.006). Rats randomized to hyperthermia developed a significantly greater degree of TCM-like dysfunction (median 19.62% (interquartile range 7.61%-25.82%) vs median 0% (interquartile range 0%-0%), p=0.00002) and a significantly higher incidence of apical ballooning (8/16 (50%) vs 0/16 (0%), p=0.002). Rats randomized to hyperthermia developed a higher mean heart rate (574 ± 21 vs 522 ± 7, p=0.002) and maximum heart rate (620 ± 14 vs 557 ± 21, p=0.0004). Conclusions: Body temperature appears to affect the development of isoprenaline-induced TCM-like dysfunction in rats