Male rats are more prone to develop Takotsubo-like cardiac dysfunction in response to high-dose catecholamine than are female rats

Purpose: Stress-induced cardiomyopathy (SIC), also known as Takotsubo cardiomyopathy, is characterized by severe but potentially reversible left ventricular dysfunction in the absence of an explanatory coronary artery obstruction. In contrast to ischemic heart disease and acute myocardial infarction, which predominantly affect males, approximately 90% of SIC patients are women. Although little is known about the pathomechanism behind the syndrome, excess levels of catecholamine are believed to play an important role. We and others have shown that SIC-like cardiac dysfunction can be induced in the rat by administration of high dose catecholamine. Recently, chronic stress has been proposed to predispose an individual to develop SIC. The aim of this manuscript was to study the effect of gender on the development of SIC-like cardiac dysfunction in rats. Methods: A total of 243 ten weeks old male (n=114) and female (n=111) Sprague-Dawley rats were used in this study. The rats were housed five in each cage according to current guidelines. At the start of the experiment the rats were injected with 50 mg/kg isoproterenol intraperitoneally, a protocol that induces SIC-like left ventricular (LV) apical ballooning. Echocardiography was used to assess extent of LV akinesia as well as indices of cardiac function. Generalized linear models, multiple regression and Cox proportional hazards models were used to determine the influence of gender, developed body temperature, orchidectomy and ovarectomy on degree of LV akinesia, cardiac function and survival. Results: In all fitted models, male gender was associated with significantly greater extent of LV akinesia and increased survival. Orchidectomy was associated with less widespread akinesia and ovarectomy with increased LV akinesia. Development of high body temperature in response to isoprenaline was associated with greater extent of LV akinesia. Conclusion: Our data indicate that male gender is associated with development of SIC-like cardiac dysfunction in rats and that development of SIC may be protective. We propose that the discrepancy between our findings and the female overrepresantation observed in the clinical setting may be explained by differences in the degree of chronic stress, i.e. that it is more stressful for male rats to be housed together than it is for female rats whereas modern society may be more stressful for women than it is for men.