TY - JOUR
T1 - Impact of mitral regurgitation on left ventricular anatomic and molecular remodeling and systolic function
T2 - Implication for outcome
AU - Pu, Min
AU - Gao, Zhaohui
AU - Zhang, Xueqian
AU - Liao, Duanping
AU - Pu, Daniel K.
AU - Brennan, Timothy
AU - Davidson, William R.
PY - 2009/6
Y1 - 2009/6
N2 - The aim of the study was to assess the impact of mitral regurgitation (MR) on left ventricular (LV) anatomic and molecular remodeling and function and to determine whether early LV remodeling and function predict long-term outcome in experimental organic MR. A new rodent model of chronic MR was created. Twenty-eight rats had surgically induced MR, twelve rats had a sham operation, and twelve rats had no operation. LV diameters, volume, and mass and LV ejection fraction (LVEF) and LV fractional shortening (LVFS) were assessed using echocardiography in the early stage of MR (6 and 12 wk after induction of MR). LV hemodynamics was assessed invasively. Cardiac α- and β-myosin heavy chains and sarco(endo)plasmic reticulum Ca2+-ATPase 2 (SERCA2) were measured to assess molecular remodeling and contractility. Cox's proportional hazard ratios (HR) were used to identify outcome predictors. Early LV dilation was demonstrated in rats with MR when LVEF and LVFS were still normal. LV remodeling was associated with an increase in LV end-diastolic pressure and decrease in maximal change in pressure over time. Shifting of α- to β-myosin and reduced SERCA2 were observed in rats with MR. Cox's proportional hazard analysis showed that LV end-diastolic diameters (HR, 1.2-2.4; P = 0.007) and LV end-diastolic volume (HR, 1.1-1.4; P = 0.005) at 6 wk and LV mass index (HR, 1.1-2.0; P = 0.004) at 12 wk after induction of MR were significantly associated with 1-yr mortality. However, LVEF (HR, 0.7-6.8 for the 6 wk, P > 0.05; and HR, 0.4-3.2 for the 12 wk, P > 0.05) and LVFS (HR, 0.4-1.4 for the 6 wk; and 0.4-3.1 for the 12 wk, P > 0.05) did not predict late death. Chronic MR leads to LV anatomic and cellular remodeling and impaired contractility. The time course of LV remodeling and function changes in the rat model of MR is similar to humans. Prediction of outcome may be achieved by assessments of early LV remodeling.
AB - The aim of the study was to assess the impact of mitral regurgitation (MR) on left ventricular (LV) anatomic and molecular remodeling and function and to determine whether early LV remodeling and function predict long-term outcome in experimental organic MR. A new rodent model of chronic MR was created. Twenty-eight rats had surgically induced MR, twelve rats had a sham operation, and twelve rats had no operation. LV diameters, volume, and mass and LV ejection fraction (LVEF) and LV fractional shortening (LVFS) were assessed using echocardiography in the early stage of MR (6 and 12 wk after induction of MR). LV hemodynamics was assessed invasively. Cardiac α- and β-myosin heavy chains and sarco(endo)plasmic reticulum Ca2+-ATPase 2 (SERCA2) were measured to assess molecular remodeling and contractility. Cox's proportional hazard ratios (HR) were used to identify outcome predictors. Early LV dilation was demonstrated in rats with MR when LVEF and LVFS were still normal. LV remodeling was associated with an increase in LV end-diastolic pressure and decrease in maximal change in pressure over time. Shifting of α- to β-myosin and reduced SERCA2 were observed in rats with MR. Cox's proportional hazard analysis showed that LV end-diastolic diameters (HR, 1.2-2.4; P = 0.007) and LV end-diastolic volume (HR, 1.1-1.4; P = 0.005) at 6 wk and LV mass index (HR, 1.1-2.0; P = 0.004) at 12 wk after induction of MR were significantly associated with 1-yr mortality. However, LVEF (HR, 0.7-6.8 for the 6 wk, P > 0.05; and HR, 0.4-3.2 for the 12 wk, P > 0.05) and LVFS (HR, 0.4-1.4 for the 6 wk; and 0.4-3.1 for the 12 wk, P > 0.05) did not predict late death. Chronic MR leads to LV anatomic and cellular remodeling and impaired contractility. The time course of LV remodeling and function changes in the rat model of MR is similar to humans. Prediction of outcome may be achieved by assessments of early LV remodeling.
KW - Animal model
KW - Molecular biology
UR - http://www.scopus.com/inward/record.url?scp=66949151442&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=66949151442&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00882.2008
DO - 10.1152/ajpheart.00882.2008
M3 - Article
C2 - 19329766
AN - SCOPUS:66949151442
SN - 0363-6135
VL - 296
SP - H1727-H1732
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6
ER -