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Cardiac Function in Transgenic Mice with Calcineurin Inhibition
Author(s) -
Gao Shumin,
Gelpi Ricardo,
Hong Chull,
Shen Youtang,
Zhai Peiyong,
Dhar Sunil K.,
Vatner Dorothy E.,
Vatner Stephen F.,
Sadoshima Junichi
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.970.46
Subject(s) - medicine , calcineurin , pressure overload , diastole , endocrinology , cardiac function curve , cardiology , muscle hypertrophy , ejection fraction , pulse pressure , diastolic function , blood pressure , cardiac hypertrophy , heart failure , transplantation
The goal of this study was to determine whether left ventricular (LV) function is altered in Zaki4 transgenic (TG) mice, which inhibit calcineurin, at baseline and with chronic pressure overload (aortic banding). LV function was measured by pulse wave and tissue Doppler. At baseline, LV ejection fraction (EF) was not different in TG and wild type (WT) mice. However, diastolic function was already impaired in TG, as reflected by mitral inflow E/A ratio 1.46±0.07 VS 1.22±0.06, P<0.05. After 2‐weeks of aortic banding, LV/BW in TG mice was significantly less than that in WT mice (3.3±0.1 VS 4.0±0.2, P<0.05) due to calcineurin inhibition. However, not only E/A ratio, but also deceleration time (DT ms), IVRT (ms), pulsed Doppler Tei index and tissue Doppler Tei index were significantly impaired in TG, and LVEF was also decreased, P<0.05, TG 66±1% VS WT 70±1%. Thus, while inhibition of calcineurin in TG mice prevents the development of LV hypertrophy, it impairs LV diastolic function, which is evident even without pressure overload. With the stress of chronic pressure overload, the diastolic dysfunction is intensified and systolic dysfunction appears.