P499The effects of aging on pathologic left ventricular remodeling and dysfunction depend critically on the underlying pathology

Abstract

The aging heart undergoes structural and functional changes that are reminiscent of the failing heart. We hypothesized that aging may increase cardiac vulnerability to develop heart failure in response to mechanical overload. To test this hypothesis, we subjected mice to pressure overload by transverse aortic constriction (TAC) or myocardial infarction (MI) at 3, 12 and 24 months of age. Eight weeks after TAC or MI, left ventricular (LV) geometry, LV function and LV weight were determined. Aging minimally affected LV geometry and function in sham operated mice. TAC produced LV hypertrophy and reduced fractional shortening in all age groups. However, only in 24 months old mice, TAC produced LV dilation and a loss of global LV contractility, demonstrated by a decrease in LVdP/dt at 40 mmHg, as well as diastolic dysfunction evidenced by a decrease in dP/dtmin and an increase in LV end diastolic pressure. In contrast, MI produced LV dilation and systolic and diastolic LV dysfunction to a similar extent in all age groups. In conclusion, the effects of aging on the cardiac response to hemodynamic overload, depend critically on the underlying pathology.