Exogenous Thyroxine Normalizes Decreased Heart Rate in Insulin Resistant OLETF Rats

Diabetic cardiomyopathy (DCM) is defined as heart failure in the absence of overt clinical coronary artery disease, valvular disease, hypertension, and dyslipidemia in diabetic patients. Patients with T2DM display left ventricular dysfunction, fibrosis, and abnormal cell signaling leading to diastolic and systolic dysfunction. Increased left ventricular mass and fibrosis potentially leads to abnormal diastolic function. Substantial data exists demonstrating both insulin-dependent and non-insulin dependent diabetes impairs left ventricular function. During insulin resistance, a metabolic shift occurs favoring fatty acid metabolism at the expense of impaired glucose metabolism, leading to lipotoxicity, increased oxidative stress, and inflammation. Thyroid hormones have shown to be cardioprotective. We have previously shown exogenous thyroxine treatment increased GLUT4 translocation and nuclear factor erythroid 2-related factor 2 (Nrf2) in cardiac tissue, demonstrating the potential to improve glucose metabolism and increase antioxidant defense mechanisms. Insulin resistant, Otsuka Long Evans Tokushima Fatty (OLETF) rats were used to assess the effects of exogenous thyroxine (T4) on left ventricular cardiac function and hemodynamics to assess if the previously observed improvements in cellular metabolism translated to functional improvements. Rats were assigned to three groups: (1) lean, Long Evans Tokushima Otsuka (LETO; n=7), (2) untreated OLETF (n=6), and (3) OLETF + T4 (8 μg/100g BM/d × 6 wks, n=7). Left ventricular function was measured by the pressure-volume system. Heart mass increased in untreated OLETF (1.46 ± 0.08) and treated OLETF (1.61 ± 0.16) compared to LETO (1.19 ± 0.08). Cardiac output (CO) and stroke volume were 26% and 56% greater in untreated OLETF compared to LETO. Heart rate (HR) was 27% lesser in untreated OLETF compared to LETO. While exogenous T4 did not alter CO and SV compared to untreated OLETF, it did normalize HR to LETO levels. The differences in CO between LETO and OLETF suggest that elevated T4 alters the mechanisms (SV vs HR) by which CO is elevated during MetS. The changes may be compensatory to accommodate the cardiac hypertrophy observed in the strain. American Heart Association Award # 946746 APS Porter Physiology Development Fellow (2nd year). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.