小鼠主动脉缩窄模型早期压力阶差与心肌肥厚程度的关系

Relationship between early pressure gradient and the degree of myocardial hypertrophy in a mouse model of transverse aortic constriction

目的小鼠压力负荷模型实验终点时压力阶差(pressure gradient,PG)与左心室肥厚程度具有明显相关性,但目前压力负荷早期PG与后期心肌肥厚完全形成阶段的心功能与心室质量相关性仍不清楚,本实验通过研究小鼠主动脉缩窄术(transverse aortic constriction,TAC)后早期PG大小在判断TAC术后主动脉收缩程度和主动脉压力大小中的作用,以及与实验终点时小鼠心肌肥厚程度与心肌收缩功能情况的相关性,为实验早期判断主动脉缩窄程度与选取实验入组小鼠提供依据。方法选取14~16周龄体重为25~26 g的C57BL/6雄性小鼠进行TAC手术,并在术前、术后1周和术后4周进行心脏超声心动图检测,术后4周时进行血流动力学检测并测量体重和左心室重量/胫骨长度(left ventricle/tibial length,LV/TL)。结果与术前相比,TAC术后1周和4周时血流速度和PG都显著性升高(P<0.05);TAC 4周时的PG与LVSP(r=0.773,P<0.001)和SBP(r=0.658,P=0.002)具有显著的相关性,表明通过无创性的超声多普勒检测与侵入性的血流动力学检测主动脉缩窄术造成的压力负荷具有高度的一致性;TAC 1周和4周时的PG都与TAC 4周时LV/TL、左心室重量指数(left ventricular mass index,LVMI)、左心室舒张末期内径(left ventricular end-diastolic diameter,LVEDd)、左心室收缩末期内径(left ventricular end-systolic diameter,LVESd)、左心室舒张期前壁厚度(left ventricular anterior wall thickness at diastole,LVAWd)、左心室舒张期后壁厚度(left ventricular posterior wall thickness at diastole,LVPWd)呈显著正相关,与射血分数(ejection fraction,EF)和缩短分数(fraction shortening,FS)呈显著负相关。结论TAC 1周时PG大小可以预测TAC 4周心肌肥厚程度,PG越大,TAC 4周时左心室重量越重、心室壁厚度和心室扩张程度越严重,心肌收缩功能受损越严重。

Objective To investigate the effect of early pressure gradient(PG)after transverse aortic constriction(TAC)on the degree of aortic constriction and aortic pressure in mice,the relationship with myocardial hypertrophy and myocardial systolic function at the experimental endpoint,and to provide a basis for the early measurement of aortic constriction and selection of experimental mice.Methods Male C57BL/6 mice aged 14~16 weeks were selected for TAC surgery.Cardiac echocardiography was performed before and 1 week and 4 weeks after the operation,and hemodynamic testing and measurement of body weight and left ventricular weight/tibial length(LV/TL)were performed 4 weeks after surgery.Results Both flow velocity and PG were significantly higher 1 and 4 weeks after TAC compared with preoperative levels(P<0.05).PG at 4 weeks after TAC was significantly correlated with left ventricular systolic pressure(r=0.773,P<0.001)and systolic blood pressure(r=0.658,P=0.002),indicating that hemodynamic testing by noninvasive ultrasound Doppler can replace the invasive hemodynamic detection of pressure caused by TAC.The PG 1 and 4 weeks after TAC was significantly and positively correlated with LV/TL,left ventricular mass index,left ventricular end-diastolic diameter,left ventricular end-systolic diameter,left ventricular anterior wall thickness at diastole,and left ventricular posterior wall thickness at diastole.In addition,both 1 week and 4 weeks after TAC,the ejection fraction and fraction shortening were significantly negatively correlated with PG.Conclusions The PG 1 week after TAC predicted the degree of myocardial hypertrophy 4 weeks after TAC,and the larger the PG,the heavier the left ventricular weight,the more severe the ventricular wall thickness and ventricular dilation 4 weeks after TAC,and the more severe the impairment to myocardial systolic function.