Age-related changes in left ventricular systolic and diastolic function and their histological and ultrastructural correlates in male WKY rats

To investigate age-related changes in left ventricular systolic function (assessed by multi-dimensional strain) and diastolic function (assessed by –dP/dt and Tau), and to explore their histological and ultrastructural correlates in male Wistar–Kyoto (WKY) rats. WKY rats were observed from 12 to 102 weeks, including echocardiography, cardiac catheterization, myocardial histology, and ultrastructure. Relative wall thickness increased at 64 weeks, left ventricular mass index and left atrial diameter increased at 72 weeks (all p < 0.05). LVEF kept normal at all weeks. Subendocardial myocardial longitudinal strain (GLS-endo) and LV ± dp/dtmax decreased at 72 weeks and declined with age, Tau increased at 84 and 102 weeks (all p < 0.05). The global collagen volume fractions (CVF) increased at 72 weeks, perivascular collagen area (PVCA) increased significantly until 102 weeks (all p < 0.05). Disorganized myofibrils and localized clustering of mitochondria appeared at 72 weeks. GLS-endo, GRS, and LV-dp/dtmax were negatively correlated with CVF-endo. Tau was positively correlated with CVF and PVCA. Multiple linear regression analysis indicated that GLS-endo and circumferential strain were independently correlated with PVCA. Age-related decline in both systolic and diastolic function are observed in male WKY rats. Systolic dysfunction manifests as reduced subendocardial strain, while diastolic dysfunction manifests as impaired relaxation. These changes likely share a common structural basis of progressive myocardial fibrosis and ultrastructural damage.