© 2007 European Society of Cardiology
Impaired contractile reserve in severe mitral valve regurgitation with a preserved ejection fraction
Cardiovascular Research Center, Temple University School of Medicine United States
* Corresponding author. Stanford University Medical Center, Department of Radiology, 300 Pasteur Drive, Stanford, CA 94305, United States. Tel.: +1 215 847 1462; fax: +1 650 723 1909. E-mail address: mcginleyjoseph{at}hotmail.com
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Abstract |
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Background: Impaired contractile reserve in chronic MR results from load-independent, myocyte contractile abnormalities.
Aims: Investigate the mechanisms of contractile dysfunction in chronic mitral valve regurgitation (MR).
Methods: Mild MR was produced in eight dogs followed by pacing induced left ventricular (LV) dilatation over eight months. In-vivo LV dP/dt was measured at several pacing rates. Contractile function was measured in isolated LV trabeculae and myocytes at several stimulation rates and during changes in extracellular [Ca2+]. Identical studies were performed with six control dogs.
Results: Chronic MR resulted in a preserved ejection fraction with decreased dP/dt (p<0.01). LV trabeculae demonstrated significantly lower developed force and a negative force–frequency relation with chronic MR (p<0.05). Myocytes exhibited a negative shortening-frequency relationship in both groups with a greater decline with chronic MR (p<0.001) paralleled by decreases in peak [Ca2+]i transients. Increases in extracellular [Ca2+] abrogated the defects in force generation in trabeculae from animals with chronic MR.
Conclusion: Even with a preserved EF, chronic severe MR results in a significant reduction in intrinsic contractile function and reserve. Functional impairment was load-independent reflecting a predominant defect in calcium cycling rather than impaired peak force generating capacity due to myofibrillar attenuation.
Key Words: Valvular disease • Mitral valve regurgitation • Myocyte physiology • Left ventricular trabecular physiology • Calcium transients • Heart failure
Received March 1, 2007; Revised April 13, 2007; Accepted May 17, 2007
This project has been supported, in part, through a grant from the Ottawa Heart Institute.
1 Current Affiliation: Stanford University, Department of Radiology, Stanford, CA, United States.
2 Current Affiliation: Cardiovascular Institute, Hospital of the University of Pennsylvania, Philadelphia, PA, United States.
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