Diastolic Properties in Older Mice: Comparison Between C57Bl6J and C57BL6N.




Taffet, George
Karim, Sanaa
Acharya, Deepak
Reddy, Anilkumar
Yechoor, Poornima
Pham, Thuy
Hermosillo, Jesus
Harley, Craig
Knebl, Janice


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Purpose: Cardiac aging in both humans and mice is associated with diastolic dysfunction, and impairment of the left ventricle filling. Age-related factors contributing to this filling impairment include fibrosis of the ventricle and impaired calcium handling by cardiomyocytes. Most aging studies use the C57Bl6/J (J mouse), but the C57Bl6/N (N mouse) has similar longevity without extensive cardiac fibrosis at comparable ages. Hence, this study is designed to identify the effect of fibrosis on diastolic function. Methods: We performed Doppler and 2-D echocardiography on fourteen 29 months old C57B16 (J and N’s) mice under 1% Isoflurane. The parameterized diastolic filling (PDF) formalism was used to comprehensively evaluate the diastolic dysfunction modeling the ventricle as a damped spring with spring stiffness (k), damping constant (c), initial stretch (x0). Small doses of Ivabradine were given to control heart rate for this assessment. Results: The N mice showed a c value of 205 ± 15, k of 7940 ± 530 and a xo of -.23 ± .004 in comparison to the J mice that showed a c value of 195 ± 14, a k value of 10,420 ± 800 and a xo value of -.016 ± .001. Conclusions: Though systolic function was preserved in old N’s and J’s, the spring stiffness (k) was significantly higher for the old J’s. This suggests fibrosis stiffens the old heart dramatically, but the larger LV diameter in the N’s suggests that fibrosis may prevent chamber enlargement with aging.