Impaired contractile reserve in severe mitral valve regurgitation with a preserved ejection fraction

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• 作者：Joseph C. McGinley ; Remus M. Berretta ; Khuram Chaudhary ; Eric Rossman ; George D. Bratinov ; John P. Gaughan ; Steven Houser ; Kenneth B. Margulies
• 关键词：Valvular disease ; Mitral valve regurgitation ; Myocyte physiology ; Left ventricular trabecular physiology ; Calcium transients ; Heart failure
• 刊名：European Journal of Heart Failure
• 出版年：2007
• 期刊代码：90_13889842
• 类别：med
• 出版时间：September 2007
• 卷：9
• 期：9
• 页码：857-864
• 文件大小：338 K

摘要

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.