CONTRACTILITY IN EXPERIMENTAL VOLUME OVERLOAD

实验体积过载中的收缩性

• 批准号: 3354269
• 负责人: BLASE A CARABELLO
• 金额: $ 11.5万
• 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/3354269
• 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.

长时间的左心室容量超载会导致