Abstract

Age-associated diastolic heart failure occurs when the amount of blood filling the heart between beats is reduced due to slow relaxation and increased passive stiffness of the left ventricle. We are testing the hypothesis that slowed active relaxation in diastolic heart failure is caused in part by age-dependent alterations in the contractile function of different transmural regions of the myocardium. Cardiac myocytes from endocardial, midmyocardial, and endocardial regions of the left ventricular free wall were isolated from hearts of 6, 18, and 22-month-old female Fischer 344 rats (n = 2 at each age). Cells were placed in a superfusion chamber controlled at 25oC and field stimulated at 0.5 Hz. Unloaded sarcomere shortening was measured in an average of 27 cells per myocardial region per animal. In five of the six animals, significant differences in relaxation (time from peak shortening to 50% re-lengthening, tp50) were observed among cell subtypes (p < 0.05, ANOVA). Analysis of collated data showed that tp50 was significantly affected by age, tending to increase in older animals (p < 0.01, two-way ANOVA). Aging appeared to have the greatest effect on relaxation of epicardial and midmyocardial cells.

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