An animal model of stress-induced cardiomyopathy utilizing the social defeat paradigm

Abstract

Stress-induced cardiomyopathy (SIC) is a form of acute heart disease triggered by extreme psychological stress. In patients who develop SIC, the outward symptoms are almost indistinguishable from acute myocardial infarction (AMI). However, some important criteria differentiate patients with SIC from those with AMI. Patients with SIC: 1) experience some form of extreme psychological stress from minutes to hours before developing heart disease, 2) do not suffer from atherosclerosis or coronary artery obstruction, and 3) exhibit abnormal ballooning of the left ventricle. In the present study, the resident-intruder (RI) social defeat test was investigated as a potential rat model for stressed-induced cardiomyopathy. Adult Long-Evans rats were implanted with a biotelemetry transmitter for ECG recordings and habituated for two weeks. An intruder rat was placed in the cage of a resident rat behind a wire-mesh partition for 5min. The partition was then removed for 5min to allow direct contact between the intruder and resident rats. After this interval, the wire-mesh partition was replaced and the intruder rat remained behind the partition for an additional 50min. Behavioral responses were noted and ECG recordings were collected during the entire 60-min testing period. Upon completion of the test, the intruder rat was removed from the cage of the resident rat and sacrificed. The heart was examined and blood was collected. Heart weight/body weight ratio, left ventricle/body weight ratio, heart length, plasma corticosterone levels, and plasma troponin I levels of intruder rats were significantly higher as compared to control rats. Intruder rats significantly increased their heart rate during the first 5min of the RI test. It is concluded that the RI test to induce social defeat is a novel rodent paradigm for modeling stress-induced cardiomyopathy in the human.