Aged murine hearts exhibited impaired sarcomere lengthening during ventricular filling and increased cardiomyocyte stiffness compared with young hearts (elastic modulus 41.9 vs 18.6 kPa; P=0.006).
Absolute Event Rate: 41.9% vs 18.6%
p-value: p=0.006
The Frank-Starling mechanism, whereby increased diastolic filling leads to increased cardiac output, depends on increasing the sarcomere length (Ls) of cardiomyocytes. Ventricular stiffness increases with advancing age, yet it remains unclear how such changes in compliance impact sarcomere dynamics in the intact heart. We developed an isolated murine heart preparation to monitor Ls as a function of left ventricular pressure and tested the hypothesis that sarcomere lengthening in response to ventricular filling is impaired with advanced age. Mouse hearts isolated from young (3-6 mo) and aged (24-28 mo) C57BL/6 mice were perfused via the aorta under Ca (2+) -free conditions with the left ventricle cannulated to control filling pressure. Two-photon imaging of 4-2-6- (dioctylamino) -2-naphthalenylethenyl1- (3-sulfopropyl) -pyridinium fluorescence was used to monitor t-tubule striations and obtain passive Ls between pressures of 0 and 40 mmHg. Ls values (in μm, aged vs. young, respectively) were 2. 02 ± 0. 04 versus 2. 01 ± 0. 02 at 0 mmHg, 2. 13 ± 0. 04 versus 2. 23 ± 0. 02 at 5 mmHg, 2. 21 ± 0. 03 versus 2. 27 ± 0. 03 at 10 mmHg, and 2. 28 ± 0. 02 versus 2. 36 ± 0. 01 at 40 mmHg, indicative of impaired sarcomere lengthening in aged hearts. Atomic force microscopy nanoindentation revealed that intact cardiomyocytes enzymatically isolated from aged hearts had increased stiffness compared with those of young hearts (elastic modulus: aged, 41. 9 ± 5. 8 kPa vs. young, 18. 6 ± 3. 3 kPa; P = 0. 006). Impaired sarcomere lengthening during left ventricular filling may contribute to cardiac dysfunction with advancing age by attenuating the Frank-Starling mechanism and reducing stroke volume.
Nance et al. (Fri,) conducted a other in Ventricular stiffness and aging. Aged murine hearts vs. Young murine hearts was evaluated on Cardiomyocyte stiffness (elastic modulus) (p=0.006). Aged murine hearts exhibited impaired sarcomere lengthening during ventricular filling and increased cardiomyocyte stiffness compared with young hearts (elastic modulus 41.9 vs 18.6 kPa; P=0.006).