CONTRACTILITY IN EXPERIMENTAL VOLUME OVERLOAD

实验体积过载中的收缩性

• 批准号: 3354271
• 负责人: BLASE A CARABELLO
• 金额: $ 12.44万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3354271
• 关键词: cineangiocardiography; congestive heart failure; disease /disorder model; dogs; heart circulation; heart contraction; intracardiac volume; mitral valve; mitral valve insufficiency; prosthetic heart valve

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.

人类长时间的左心体积超负荷导致 收缩功能降低和泵的性能不佳。 这 导致收缩功能障碍的机制很难 由于明显的道德限制，在人类中进行研究，因为 从体积开始时很少有病人 在经过补偿的偏心期间超负荷 肥大到心室功能障碍。 实验 体积超载模型对于研究 发生的心室功能障碍的机制，但 不幸的是，这些模型通常不会产生左心室 功能障碍。 因此，右心体积超负荷的模型 （可能不是左心体积 超负荷）没有产生收缩的赤字。 左边 使用完整心脏障碍或的心室模型 各种AV瘘通常显示出正常的收缩 功能虽然一个这样的模型确实证明了收缩 赤字。 在此提案中，我们将研究纯卷的收缩功能 二尖瓣的独特闭合胸部产生的超负荷 反流。 我们将使用圆周的平均速度 纤维缩短压力关系，这是相对负载的 独立，纵向评估收缩功能 体积超负荷肥大的发展。 使用此试点数据 模型表明，实际上确实发生了收缩赤字。 如果a 确实发生了收缩赤字，我们将尝试 确定赤字是否是财产 由体积产生的异常腔室几何形状 过载或固有的心肌细胞 功能障碍。 在更临床的层面上，很明显二尖瓣 阀门更换导致泵性能下降 术后。 性能下降范围从轻度 严重但几乎总是发生，通常是不可逆的。 虽然这秋天的泵的传统解释 性能是由于由于 将低阻抗途径拆除到左心房 点是有争议的。 在此提案中，我们将执行二线 慢性二尖瓣反流中的瓣膜更换。 然后我们会 以系统的方式检查1）减少收缩 性能，2）增加后负载，3）无能为力 肥大以抵消增加后负载的增加，4）去除 乳头状二尖瓣复合物作为可能的机制 术后性能下降后二尖瓣值 替代品。