Severe impairment of ventricular compliance accounts for advanced age-associated hemodynamic dysfunction in rats

Advanced aging is associated with hemodynamic dysfunction in rats as in humans. The aim of this study was to assess the mechanisms of development of left ventricular (LV) dysfunction in the rat model of aging. In vivo hemodynamics and ex vivo LV papillary muscle mechanics, myofilaments sensitivity to calcium in skinned fibers and pressure/volume curves in isolated perfused hearts were performed in 3, 24 and 28 month old (mo) male Wistar rats. Hemodynamic dysfunction occurs in 28 mo rats and is characterized by both a systolic and diastolic dysfunction and a LV hypertrophy (+34.7% of LV weight). In papillary muscle, normalized active developed force and myofilament sensitivity to calcium were unchanged between 24 and 28 months of age. In contrast, both resting force/total force ratio in papillary muscle and the slope of the pressure/volume curves in isolated heart are increased between 3 and 24 mo but also between 24 and 28 mo, indicating a progression of the impairment of both papillary muscle stiffness and LV compliance in advanced aging. Hemodynamic dysfunction occurring at advanced age, i.e. 28 mo in rats mainly results from impairment of ventricular compliance resulting from fibrosis.