Noninvasive assessment of murine pulmonary arterial pressure: validation and application to models of pulmonary hypertension.
Noninvasive assessment of murine pulmonary arterial pressure: validation and application to models of pulmonary hypertension.
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DOI：
10.1161/circimaging.109.887109
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发表时间：
2010-03
期刊：
影响因子：
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通讯作者：
Scherrer-Crosbie M
中科院分区：
文献类型：
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作者：
Thibault HB;Kurtz B;Raher MJ;Shaik RS;Waxman A;Derumeaux G;Halpern EF;Bloch KD;Scherrer-Crosbie M
转基因小鼠为深入了解肺动脉高压(PAH)的病理生理学提供了独特的机会。在小鼠身上，右心导管术是测量右室收缩压(RVSP)的唯一可用的技术。但是，这是一个终端程序，不允许连续测量。我们的目标是验证一种非侵入性技术来评估小鼠的RVSP。对静脉注射血栓素类似物U-46619急性或慢性肺组织特异性白介素6(IL-6)过度表达所致肺动脉高压的小鼠，同时行右心室插管和超声心动图(30 MHz探头)。在胸骨旁短轴切面用脉冲多普勒技术测量肺加速时间(PAT)和射血时间(ET)。输注U-46619可显著增加右室压，缩短PAT，降低PAT/ET。肺血流模式从基线时的对称性变为高RVSP时的不对称性。在野生型和IL-6过度表达的小鼠中，PAT与RVSP呈线性相关(R2=−0.67；p<；0.0001)，PAT/ET也是如此(R2=−0.76；p<；0.0001)。两种指标检测高RVSP的敏感性和特异性分别为100%(7/7)和86%(6/7)(截断值：PAT和ET分别为21ms和39%)。PAT和PAT/ET的观察者内和观察者间变异小于6%。在小鼠中，右室收缩压可以无创地估计。超声心动图能够检测RVSP的急性和慢性升高，具有很高的敏感性和特异性，并能评估RVSP的治疗效果。这种非侵入性的技术可能允许对转基因小鼠中多环芳烃的进化进行表征。
Genetically-modified mice offer the unique opportunity to gain insights into the pathophysiology of pulmonary arterial hypertension (PAH). In mice, right heart catheterization is the only available technique to measure right ventricular systolic pressure (RVSP). However, it is a terminal procedure and does not allow for serial measurements. Our objective was to validate a non-invasive technique to assess RVSP in mice. Right ventricle catheterization and echocardiography (30-MHz transducer) were simultaneously performed in mice with pulmonary hypertension induced acutely by infusion of a thromboxane analogue, U-46619, or chronically by lung-specific over-expression of interleukin 6 (IL-6). Pulmonary acceleration time (PAT) and ejection time (ET) were measured in the parasternal short axis view by pulsed-wave Doppler of pulmonary artery flow. Infusion of U-46619 acutely increased RVSP, shortened PAT, and decreased PAT/ET. The pulmonary flow pattern changed from symmetric at baseline to asymmetric at higher RVSPs. In wild-type and IL-6-over-expressing mice, the PAT correlated linearly with RVSP (r2=−0.67; p<0.0001), as did PAT/ET (r2=−0.76; p<0.0001). Sensitivity and specificity for detecting high RVSP (>32 mmHg) were 100% (7/7) and 86% (6/7), respectively, for both indices (cutoff values: PAT <21 ms and PAT/ET <39%). Intra-observer and inter-observer variability of PAT and PAT/ET were less than 6%. Right ventricular systolic pressure can be estimated non-invasively in mice. Echocardiography is able to detect acute and chronic increases in RVSP with high sensitivity and specificity, as well as to assess the effects of treatment on RVSP. This non-invasive technique may permit the characterization of the evolution of PAH in genetically-modified mice.