Magnetic resonance imaging of progressive cardiomyopathic changes in the db/db mouse

Patrick Yue, Takayasu Arai, Masahiro Terashima, Ahmad Y. Sheikh, Feng Cao, David Charo, Grant Hoyt, Robert C. Robbins, Euan A. Ashley, Joseph Wu, Phillip C. Yang, Philip S. Tsao

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

The db/db mouse is a well-established model of diabetes. Previous reports have documented contractile dysfunction (i.e., cardiomyopathy) in these animals, although the extant literature provides limited insights into cardiac structure and function as they change over time. To better elucidate the natural history of cardiomyopathy in db/db mice, we performed cardiac magnetic resonance (CMR) scans on these animals. CMR imaging was conducted with a 4.7-T magnet on female db/db mice and control db/+ littermates at 5, 9, 13, 17, and 22 wk of age. Gated gradient echo sequences were used to obtain cineographic short-axis slices from apex to base. From these images left ventricular (LV) mass (LVM), wall thickness, end-diastolic volume (LVEDV), and ejection fraction (LVEF) were determined. Additionally, cardiac [18F]fluorodeoxyglucose ([ 18F]FDG) PET scanning, pressure-volume loops, and real-time quantitative PCR on db/db myocardium were performed. Relative to control, db/db mice developed significant increases in LVM and wall thickness as early as 9 wk of age. LVEDV diverged slightly later, at 13 wk. Interestingly, compared with the baseline level, LVEF in the db/db group did not decrease significantly until 22 wk. Additionally, [18F]FDG metabolic imaging showed a 40% decrease in glucose uptake in db/db mice. Furthermore, contractile dysfunction was observed in 15-wk db/db mice undergoing pressure-volume loops. Finally, real-time quantitative PCR revealed an age-dependent recapitulation of the fetal gene program, consistent with a myopathic process. In summary, as assessed by CMR, db/db mice develop characteristic structural and functional changes consistent with cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)H2106-H2118
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

Keywords

  • Diabetes mellitus
  • Heart failure
  • Insulin resistance
  • Metabolism

ASJC Scopus subject areas

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

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