Author:
Zhou Yu-Qing,Zhu Yonghong,Bishop Jonathan,Davidson Lorinda,Henkelman R. Mark,Bruneau Benoit G.,Foster F. Stuart
Abstract
Tbx5 del/+ mice provide a model of human Holt-Oram syndrome. In this study, the cardiac functional phenotypes of this mouse model were investigated with 30-MHz ultrasound by comparing 12 Tbx5 del/+ mice with 12 wild-type littermates at 1, 2, 4, and 8 wk of age. Cardiac dimensions were measured with two-dimensional and M-mode imaging. The flow patterns in the left and right ventricular inflow channels were evaluated with Doppler flow sampling. Compared with wild-type littermates, Tbx5 del/+ mice showed significant changes in the mitral flow pattern, including decreased peak velocity of the left ventricular (LV) early filling wave (E wave), increased peak velocity of the late filling wave (A wave), and decreased or even reversed peak E-to-A ratio. The prolongation of LV isovolumic relaxation time was detected in Tbx5 del/+ neonates as early as 1 wk of age. In Tbx5 del/+ mice, LV wall thickness appeared normal but LV chamber dimension was significantly reduced. LV systolic function did not differ from that in wild-type littermates. In contrast, the Doppler flow spectrum in the enlarged tricuspid orifice of Tbx5 del/+ mice demonstrated increased peak velocities of both E and A waves and increased total time-velocity integral but unchanged peak E/A. In another 13 mice (7 Tbx5 del/+, 6 wild-type) at 2 wk of age, significant correlation was found between Tbx5 gene expression level in ventricular myocardium and LV filling parameters. In conclusion, the LV diastolic function of Tbx5 del/+ mice is significantly deteriorated, whereas the systolic function remains normal.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
47 articles.
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