Attenuated sarcomere lengthening of the aged murine left ventricle observed using two-photon fluorescence microscopy

Michael E. Nance, Justin T. Whitfield, Yi Zhu, Anne K. Gibson, Laurin M. Hanft, Kenneth S. Campbell, Gerald A. Meininger, Kerry S. McDonald, Steven S. Segal, Timothy L. Domeier

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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) C57BLs mice were perfused via the aorta under Ca2+-free conditions with the left ventricle cannulated to control filling pressure. Two-photon imaging of 4-{2-[6-(dioctylamino)-2-naphthalenyl]ethenyl}1-(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 mm, 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.

Original languageEnglish
Pages (from-to)H918-H925
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume309
Issue number5
DOIs
StatePublished - Sep 3 2015

Bibliographical note

Publisher Copyright:
© 2015 the American Physiological Society.

Keywords

  • Aging
  • Cardiomyocyte
  • Stiffness

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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