超声心动图评估低氧性肺动脉高压小鼠模型右心室收缩压

目的 以超声心动图监测单纯低氧及低氧联合血管内皮生长因子受体抑制剂SU5416诱导低氧性肺动脉高压(PH)小鼠模型心脏相关参数,据此建立预测右心室收缩压(RVSP)方程。方法 将24只C57BL/6J雄性小鼠随机分为单纯低氧组(A组)、低氧联合SU5416组(B组)及对照组(C组),每组8只。对A、B组分别以单纯低氧法及低氧联合SU5416构建低氧性PH模型。于造模前及后(开始干预后2、3、4周)行超声心动图检查,获得相关参数;于末次超声检查后以心导管法测量RVSP。观察各组超声参数变化,以及造模后4周超声参数与RVSP的相关性,建立直线方程预测RVSP。结果 开始干预后,随时间延长,A、B组肺动脉内径(PAD)、PAD/主动脉内径(AOD)及右心室前壁厚度(RVAWT)均增大,心率、肺动脉射血加速时间(PAAT)、PAAT/肺动脉射血时间(PAET)及三尖瓣环收缩期位移(TAPSE)均下降(P均＜0.05)。开始干预后3、4周,B组PAET、PAAT/PAET、TAPSE均低于A组(P＜0.05)。开始干预后4周,A、B组RVSP均与PAD/AOD、RVAWT、PAAT、PAAT/PAET及TAPSE呈高度相关(P均＜0.05)。以PAAT/PAET、TAPSE预测单纯低氧PH小鼠模型RVSP的直线回归方程为RVSP=－161.7×(PAAT/PAET)+63.85、RVSP=－36.53×TAPSE+71.55,预测低氧联合SU5416 PH小鼠模型RVSP的直线回归方程为RVSP=－266.4×(PAAT/PAET)+91.59、RVSP=－69.14×TAPSE+116.5。 结论 开始干预后4周,以单纯低氧及低氧联合SU5416构建的PH小鼠表型更为明显;根据超声心动图所获PAAT/PAET及TAPSE构建的预测PH模型小鼠RVSP方程可为相关研究提供参考。

Echocardiography for evaluating right ventricular systolic pressure of hypoxic pulmonary hypertension mouse models

Objective To monitor heart-related parameters of hypoxic pulmonary hypertension (PH) mouse models induced by hypoxia alone and hypoxia combined with vascular endothelial growth factor receptor inhibitor SU5416 using echocardiography, and to construct the prediction equation of right ventricular systolic pressure (RVSP). Twenty-four C57BL/6J male mice were randomly divided into simple hypoxia group (group A), hypoxia combined with SU5416 group (group B), control group (group C), each group 8 mice. Hypoxic PH models were constructed with hypoxia alone and hypoxia combined with SU5416 in group A and group B, respectively. Echocardiography was performed before and during modeling (2, 3, 4 weeks after interventions), and the relevant parameters were obtained. RVSP was measured using right heart catheterization after the last echocardiography. The changes of ultrasonic parameters were observed, the correlations of ultrasonic parameters 4 weeks after intervention with RVSP were observed, and linear equations for predicting RVSP were established. Results With time going, during modeling, pulmonary artery diameter (PAD), PAD/aorta diameter (AOD) and right ventricle anterior wall thickness (RVAWT) increased, while heart rate, pulmonary artery acceleration time (PAAT), PAAT/pulmonary artery ejection time (PAET) and tricuspid annular plane systolic excursion (TAPSE) decreased in group A and B (all P＜0.05). Three and 4 weeks after interventions, PAET, PAAT/PAET and TAPSE in group B decreased compared with those in group A (all P＜0.05). Four weeks after interventions, RVSP in group A and B were highly correlated with PAD/AOD, RVAWT, PAAT, PAAT/PAET and TAPSE (all P＜0.05). The linear regression equations of PAAT/PAET and TAPSE for predicting RVSP in simple hypoxic PH mice models included RVSP=－161.7×(PAAT/PAET)+63.85, as well as RVSP=－36.53×TAPSE+71.55, while of predicting RVSP in hypoxia combined with VEGFR-2 inhibitor PH mouse models were as follows: RVSP=－266.4×(PAAT/PAET)+91.59, RVSP=－69.14×TAPSE+116.5. Conclusion Four weeks after inerventions, the phenotypes of hypoxic PH mouse models induced by hypoxia alone and hypoxia combined with SU5416 became obvious. Prediction equations of RVSP established based on PAAT/PAET and TAPSE obtained with echocardiography could provide references for relevant research.