Urabe Y, Mann D L, Kent R L, Nakano K, Tomanek R J, Carabello B A, Cooper G
Veterans Administration Medical Center, Charleston, SC 29403.
Circ Res. 1992 Jan;70(1):131-47. doi: 10.1161/01.res.70.1.131.
This study was designed to answer two questions. First, does the left ventricular contractile dysfunction resulting from mitral regurgitation (MR) reflect a primary defect in the cardiac muscle cell? Second, what is the basis for any change in cellular contractile function that might be observed? Left ventricular volume overload was produced in 10 dogs by catheter transection of mitral chordae tendineae. Three months later in these and in seven control dogs, left ventricular contractile function was characterized by the end-ejection stress-volume relation (EESVR). Investigators who were blinded to these results then characterized the contractile performance of cardiac muscle cells, or cardiocytes, from these same left ventricles in terms of the viscosity (graded external load)-velocity relation. Finally, the tissue and cellular components of these same left ventricles were analyzed morphometrically. Both the left ventricles from the MR group and their constituent cardiocytes showed marked contractile abnormalities. By matching ventricles with cells from the same MR dogs, ventricular EESVR was correlated with cardiocyte peak sarcomere shortening velocity (SSV). The correlation coefficient between EESVR and SSV was 0.63, but between a size-independent measure of active ventricular stiffness and SSV, it was 0.88. No change in left ventricular interstitial volume fraction was found in MR dogs, but both ventricular and cellular contractile dysfunction strongly correlated with a decreased volume fraction of cardiocyte myofibrils. Last, in an attempt to relate the degree of contractile dysfunction to the hypertrophic response, left ventricular mass in the MR dogs was correlated with both cellular and ventricular contractile indexes; no significant correlation was found. Three conclusions are warranted by these studies. First, chronic left ventricular volume overload from mitral regurgitation leads to contractile defects at both the ventricular and cellular levels, the extent of which correlates well in individual animals. Second, no quantitative interstitial change resulted from MR. Taken together, these two findings strongly suggest that the contractile defect is intrinsic to the cardiocyte. Third, while the contractile abnormality in MR remains undefined, the most basic defects appear to be a combination of myofibrillar loss with the failure of compensatory hypertrophy to occur in response to progressive decrements in cellular and ventricular function.
本研究旨在回答两个问题。其一，二尖瓣反流（MR）导致的左心室收缩功能障碍是否反映心肌细胞的原发性缺陷？其二，可能观察到的细胞收缩功能变化的基础是什么？通过经导管横断二尖瓣腱索，在10只犬身上造成左心室容量超负荷。三个月后，对这些犬以及7只对照犬，采用射血末期应力-容积关系（EESVR）来表征左心室收缩功能。然后，对这些结果不知情的研究人员根据黏度（分级外部负荷）-速度关系，对来自相同左心室的心肌细胞（即心肌纤维细胞）的收缩性能进行表征。最后，对相同左心室的组织和细胞成分进行形态计量分析。MR组的左心室及其组成的心肌纤维细胞均表现出明显的收缩异常。通过将来自相同MR犬的心室与细胞进行匹配，心室EESVR与心肌纤维细胞肌节缩短峰值速度（SSV）相关。EESVR与SSV之间的相关系数为0.63，但在与大小无关的主动心室僵硬度测量值与SSV之间，相关系数为0.88。在MR犬中未发现左心室间质容积分数有变化，但心室和细胞收缩功能障碍均与心肌纤维细胞肌原纤维容积分数降低密切相关。最后，为了试图将收缩功能障碍程度与肥厚反应联系起来，对MR犬的左心室质量与细胞和心室收缩指标进行了相关性分析；未发现显著相关性。这些研究得出三个结论。其一，二尖瓣反流导致的慢性左心室容量超负荷会在心室和细胞水平上导致收缩缺陷，在个体动物中，其程度具有良好的相关性。其二，MR未导致定量的间质变化。综合这两个发现强烈表明收缩缺陷是心肌纤维细胞固有的。其三，虽然MR中的收缩异常仍未明确，但最基本的缺陷似乎是肌原纤维丢失与未能对细胞和心室功能的逐渐下降产生代偿性肥大反应的组合。
