CONTRACTILITY IN EXPERIMENTAL VOLUME OVERLOAD

实验体积过载中的收缩性

• 批准号: 3354266
• 负责人: BLASE A CARABELLO
• 金额: $ 10.89万
• 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/3354266
• 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.

男性长期左心室容量超负荷会导致 收缩功能减弱和泵性能差。 这 导致收缩功能障碍的机制很难确定 由于明显的道德约束，并且因为 很少有患者从发病开始就得到随访 补偿偏心期间的过载 肥厚到心室功能障碍的程度。 实验性的 容量超载模型将有助于研究 发生心室功能障碍的机制 不幸的是，这些模型通常不会产生左心室 功能障碍。 因此，右心室容量超负荷模型 （这可能与左心室容积没有密切关系 超负荷）没有产生收缩缺陷。 左边 使用完全心脏传导阻滞的心室模型或 各种动静脉瘘通常表现出正常的收缩力 尽管其中一个模型确实展示了收缩性 赤字。 在本提案中，我们将研究纯体积的收缩函数 由独特的二尖瓣闭胸模型产生的过载 反流。 我们将使用圆周的平均速度 纤维缩短-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。 使用此试点数据 模型表明实际上确实发生了收缩缺陷。 IFA 合同赤字确实发生，我们将尝试 确定赤字是否属于 体积产生的异常腔室几何形状 超负荷或由于内在心肌细胞 功能障碍。 在更临床的层面上，很明显二尖瓣 更换阀门会导致泵性能下降 术后。 这种性能下降程度从轻微到 严重但几乎总是发生并且通常是不可逆转的。 虽然对泵的下降的传统解释是 性能是由于后负荷增加所致 去除进入左心房的低阻抗通路 点是有争议的。 在本提案中，我们将进行二尖瓣手术 慢性二尖瓣反流的瓣膜置换术。 我们随后将 系统地检查 1) 收缩力减弱 性能，2）增加后负荷，3）无法额外 肥大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可能的机制 二尖瓣值术后表现下降 替代品。