CONTRACTILITY IN EXPERIMENTAL VOLUME OVERLOAD

长期的男性左心室容量超负荷导致 收缩功能降低，泵性能差。这个 导致收缩功能障碍的机制很难确定 在人类身上学习是因为明显的伦理限制和因为 很少有患者从开始量起就被随访。 补偿偏心期间的过载 肥大到心脏功能不全的程度。实验 容量超载的模型将有助于研究 发生心功能不全的机制 不幸的是，这些模型通常不会产生左心室 功能障碍。因此，右室容量超负荷的模型 (它们可能与左心室容量无关 超载)没有产生可收缩的赤字。左边 使用完全性心脏传导阻滞或 各种房室瘘通常表现为正常的收缩。 功能，尽管有一个这样的模型确实展示了收缩 赤字。 在这个提案中，我们将研究纯体积中的收缩函数 由一种独特的二尖瓣闭合胸腔模型产生的过载 反胃。我们将使用圆周平均速度 纤维缩短-应力关系，这是相对载荷 独立的，纵向评估收缩功能，如 出现容量超负荷肥大。使用此选项的试点数据 模型表明，实际上确实出现了收缩赤字。如果A 收缩赤字确实发生了，我们将尝试 确定赤字是否是政府的财产 由体积产生的异常腔体几何形状 超负荷或由固有心肌细胞引起 功能障碍。在更临床的层面上，二尖瓣明显 更换阀门会导致泵性能下降 手术后。这种性能下降的范围从轻微到 到严重，但几乎总是发生，通常是不可逆转的。 虽然传统上对水泵价格下跌的解释 性能是由于以下原因导致后负荷增加 切除进入左心房的低阻抗通路 Point是有争议的。在本提案中，我们将执行二尖瓣手术 慢性二尖瓣反流的瓣膜置换术。到时候我们会的 系统地检查收缩功能减退 性能，2)增加后负荷，3)无法增加 肥厚以抵消增加的后负荷，以及4)去除 乳头状二尖瓣复合体作为二尖瓣病变的可能机制 二尖瓣关闭不全术后表现下降 替补。

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.