Left Ventricular Dysfunction and Remodeling in Streptozotocin-Induced Diabetic Rats

Background It is not fully clarified how diabetes mellitus (DM)-induced cardiac dysfunction is associated with histopathological changes of the heart in a long lasting period of DM. Methods and Results Eighteen weeks after a streptozotocin injection was given to Wistar - Kyoto rats (D rats), echocardiography and hemodynamic studies including the dobutamine infusion test were performed. After perfusion fixation, immunofluorescent staining and histopathology of the heart were analyzed, and analysis with electron microscopy was also conducted. Systolic blood pressure in the conscious state and left ventricular (LV) ejection fraction by 2-dimensional echocardiography were reduced in D rats. LV mechanical responses to dobutamine assessed by maximal LV pressure derivative (+LVdP/dt) also decreased with higher dobutamine doses in D rats. Although LV and right ventricular (RV) wall thickness were smaller in D rats, there were increased RV volumes, indicating LV and RV dilatational remodeling in D rats. The cardiomyocyte transverse diameter and actin staining in cardiomyocytes in both the LV and RV were significantly reduced, and capillary tortuosity and type IV collagen were increased, indicating microangiopathy in D rats. Conclusions Advanced insulin-dependent DM incurred not only RV remodeling but also overt resting LV systolic dysfunction and decreased LV responsiveness to β adrenergic stimulation with dilatational remodeling, accompanied by pathological changes of capillaries and cardiomyocytes including actin filaments. (Circ J 2006; 70: 327 - 334)