Tsutsui H, Urabe Y, Mann D L, Tagawa H, Carabello B A, Cooper G, Zile M R
Gazes Cardiac Research Institute, Cardiology Division of the Department of Medicine, Medical University of South Carolina, Charleston 29425-5799.
Circ Res. 1993 May;72(5):1110-23. doi: 10.1161/01.res.72.5.1110.
We have previously shown that chronic mitral regurgitation (MR) increases the rate of left ventricular early diastolic filling. These changes in chamber diastolic function were felt to be secondary to alterations in left ventricular loading conditions. Therefore, cellular diastolic function measured in cardiac muscle cells (cardiocytes) isolated from animals with chronic MR (absent alterations in loading conditions) was expected to be normal. However, chronic MR caused a decrease in sarcomere lengthening rate. The purpose of the current study was to define the mechanisms causing this decreased sarcomere lengthening rate in chronic MR cardiocytes and to explain the apparent dichotomy between chamber and cellular diastolic properties. Accordingly, sarcomere motion was measured using laser diffraction techniques in enzymatically isolated cardiocytes from seven control dogs and 11 dogs with chronic MR (produced by closed-chest transection of the mitral chordae). In the MR cardiocytes, there were abnormalities in cellular systolic function (decreased extent and velocity of shortening) and in cellular diastolic function (decreased velocity of sarcomere lengthening). Because studies in papillary muscles have shown that there is a direct relation between abnormal diastolic function (decreased velocity of muscle lengthening) and abnormal systolic function (decreased extent of muscle shortening), it was unclear whether the changes in cellular relaxation rate observed in chronic MR merely reflected a concomitant decrease in the extent of shortening or instead reflected an impairment in intrinsic relaxation properties. To make this distinction, the relation between relaxation velocity (measured as peak sarcomere lengthening rate) and sarcomere shortening extent was examined in MR cardiocytes and compared with that in control cardiocytes. There was a direct relation between sarcomere relaxation velocity and sarcomere shortening extent in both control and MR cardiocytes. Over a wide range of shortening extent, the slopes and y intercepts of this relation were similar in control and MR cardiocytes (slope, 27.7 sec-1 in control cells versus 28.1 sec-1 in MR cells; y intercept, -1.1 microns/sec in control cells versus -1.7 microns/sec in MR cells; p = NS). At any common shortening extent, relaxation velocity was the same in control and MR cardiocytes. To prove that this relation could detect abnormalities in the intrinsic myocardial relaxation process, interventions known to produce primary alterations in the intrinsic myocardial relaxation process were examined: the effects of hypothermia (30 degrees C) and isoproterenol (10(-6) M) on the relaxation velocity-shortening extent relation were studied in normal and MR cardiocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
我们之前已经表明，慢性二尖瓣反流（MR）会增加左心室舒张早期充盈率。这些心室舒张功能的变化被认为是左心室负荷条件改变的继发结果。因此，预计从患有慢性MR的动物（负荷条件无改变）分离出的心肌细胞（心肌细胞）中测量的细胞舒张功能是正常的。然而，慢性MR导致肌节延长率降低。本研究的目的是确定导致慢性MR心肌细胞中肌节延长率降低的机制，并解释心室和细胞舒张特性之间明显的二分法。因此，使用激光衍射技术在来自7只对照犬和11只患有慢性MR的犬（通过二尖瓣腱索的闭胸横断产生）的酶分离心肌细胞中测量肌节运动。在MR心肌细胞中，细胞收缩功能存在异常（缩短程度和速度降低）以及细胞舒张功能异常（肌节延长速度降低）。因为在乳头肌中的研究表明，舒张功能异常（肌肉延长速度降低）和收缩功能异常（肌肉缩短程度降低）之间存在直接关系，所以尚不清楚在慢性MR中观察到的细胞舒张率变化仅仅是反映了缩短程度的伴随降低，还是相反反映了内在舒张特性的损害。为了区分这一点，在MR心肌细胞中检查了舒张速度（以肌节延长峰值速率测量）与肌节缩短程度之间的关系，并与对照心肌细胞进行比较。在对照和MR心肌细胞中，肌节舒张速度与肌节缩短程度之间均存在直接关系。在很宽的缩短程度范围内，对照和MR心肌细胞中这种关系的斜率和y轴截距相似（斜率，对照细胞中为27.7秒-1，MR细胞中为28.1秒-1；y轴截距，对照细胞中为-1.1微米/秒，MR细胞中为-1.7微米/秒；p =无显著性差异）。在任何共同的缩短程度下，对照和MR心肌细胞中的舒张速度相同。为了证明这种关系可以检测到心肌内在舒张过程中的异常，研究了已知会引起心肌内在舒张过程原发性改变的干预措施：在正常和MR心肌细胞中研究了低温（30摄氏度）和异丙肾上腺素（10^(-6) M）对舒张速度-缩短程度关系的影响。（摘要截断于400字）
