CONTRACTILITY IN EXPERIMENTAL VOLUME OVERLOAD

长期左心室容量超负荷导致 收缩功能降低和泵性能差。 的 导致收缩功能障碍的机制很难 因为明显的伦理约束， 很少有患者从其体积开始就被跟踪， 过补偿偏心周期过载 肥大到心室功能障碍的程度。 实验 容量超负荷模型将有助于研究 发生心室功能障碍的机制， 不幸的是，这些模型通常不产生左心室 功能障碍 因此，右心室容量超负荷模型 （可能与左心室容积无关 超负荷）并没有产生收缩赤字。 左 心室模型使用了完全性心脏传导阻滞或 各种动静脉瘘通常表现出正常的收缩 尽管一个这样的模型确实证明了收缩功能， 赤字 本文将研究纯体积中的收缩函数 由二尖瓣的独特闭合胸部模型产生的过载 返流程度 我们将使用圆周的平均速度 纤维短缩-应力关系，即相对载荷 独立，纵向评估收缩功能， 出现容量超负荷肥大。 试点数据使用此 模型表明，事实上，收缩赤字确实发生。 如果 如果出现机械故障，我们将尝试 确定缺陷是否是 体积产生的异常腔体几何形状 超负荷或由于固有心肌细胞 功能障碍。 在更临床的水平上，很明显二尖瓣 阀门更换导致泵性能下降 手术后。 这种性能下降的范围从轻微的 但几乎总是发生，通常是不可逆的。 虽然对泵量下降的传统解释 性能是，这是由于增加后负荷，由于 去除进入左心房的低阻抗通路， 这一点有争议。 在本提案中，我们将执行二尖瓣 慢性二尖瓣返流的瓣膜置换术 然后我们将 以系统的方式检查1）收缩减少 性能，2）增加后负荷，3）无法额外的 肥大，以抵消增加的后负荷，和4）去除 乳头状二尖瓣复合体可能是 二尖瓣关闭不全术后性能下降 更换.

Prolonged left ventricular volume overload in man results in reduced contractile function and poor pump performance. The mechanisms leading to contractile dysfunction are difficult to study in man because of obvious ethical constraints and because few patients are ever followed from the onset of their volume overload through the period of compensated eccentric hypertrophy to the point of ventricular dysfunction. Experimental models of volume overload would be useful in studying the mechanisms of ventricular dysfunction that occur but unfortunately these models usually do not produce left ventricular dysfunction. Thus, models of right ventricular volume overload (which are probably not germane to left ventricular volume overload) have not produced a contractile deficit . Left ventricular models which have used complete heart block or various AV fistulas have usually demonstrated normal contractiles function although one such model did demonstrate a contractile deficit. In this proposal we will study contractile function in pure volume overload as produced by a unique closed chest model of mitral regurgitation. We will use the mean velocity of circumferential fiber shortening-stress relationship, which is relatively load independent, to assess contractile function longitudinally as volume overload hypertrophy develops. Pilot data using this model suggests that in fact a contractile deficit does occur. IF A CONTRACTILE DEFICIT DOES OCCUR, WE WILL ATTEMPT TO ASCERTAIN WHETHER THE DEFICIT IS A PROPERTY OF THE ABNORMAL CHAMBER GEOMETRY PRODUCED BY VOLUME OVERLOAD OR DUE TO INTRINSIC MYOCARDIAL CELLULAR DYSFUNCTION. On a more clinical level it is obvious that mitral valve replacement results in a fall in pump performance postoperatively. This diminution in performance ranges from mild to severe but almost always occurs and is usually irreversible. While the traditional explanation for this fall in pump performance is that it is due to increased afterload due to removal of the low impedence pathway into the left atrium this point is controversial. In this proposal we will perform mitral valve replacement in chronic mitral regurgitation. We will then examine in a systematic fashion 1) reduced contractile performance, 2) increased afterload, 3) inability of additional hypertrophy to offset the increased afterload, and 4) removal of the papillary mitral complex as possible mechanisms for the postoperative fall in performance seen following mitral value replacement.