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Am J Physiol Heart Circ Physiol (March 27, 2009). doi:10.1152/ajpheart.00882.2008
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Submitted on August 10, 2008
Revised on January 21, 2009
Accepted on March 13, 2009

Impact of Mitral Regurgitation on Left Ventricular Anatomic and Molecular Remodeling and Systolic Function: Implication for Outcome

Min Pu1*, Zhaohui Gao2, Xeuqian Zhang2, Duanping Liao2, Daniel K Pu1, Timothy Brennan1, and William R Davidson2

1 Ohio State University
2 Penn State University

* To whom correspondence should be addressed. E-mail: min.pu{at}osumc.edu.

Aim of the study: 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. Methods: 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, mass, ejection fraction (LVEF) and fractional shortening (LVFS) were assessed using echocardiography in the early stage of MR (6 and 12 weeks after induction of MR). LV hemodynamics was assessed invasively. Cardiac {alpha}- and {beta}-myosin heavy chains and sarcoplasmic-reticulum calcium ATPase (SERCA2) were measured to assess molecular remodeling and contractility. Cox's proportional hazard ratios (HR) were used to identify outcome predictors. Results: Early LV dilation was demonstrated in rats with MR when LVEF and LVFS were still normal. LV remodeling was associated with increase in LV end-diastolic pressure and decrease in dP/dtmax. Shifting of {alpha}- to {beta}-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 weeks and LV mass index (HR 1.1-2.0 p=0.004) at 12 weeks after induction of MR were significantly associated with one-year mortality. However, LVEF (HR 0.7-6.8 for the 6-week, p>0.05; HR 0.4-3.2 for the 12-week, p>0.05) and LVFS (HR 0.4-1.4 for the 6-week; 0.4-3.1 for the 12-week, p>0.05) did not predict late death. Conclusion: 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.







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