Schwenke Daryl O, Pearson James T, Mori Hidezo, Shirai Mikiyasu
Department of Cardiac Physiology, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
J Pharmacol Toxicol Methods. 2006 May-Jun;53(3):277-83. doi: 10.1016/j.vascn.2005.11.003. Epub 2005 Dec 9.
The ability to genetically engineer specific gene 'knock-out' mice has provided a powerful tool for investigating the various mechanisms that contribute to the pathogenesis of pulmonary arterial hypertension (PAH). Yet, so far there have been no reports describing the measurement of pulmonary arterial pressure (PAP) in the conscious wild type mouse-an essential requirement for monitoring dynamic changes associated with the pathogenesis of PAH. Therefore, in this study we describe a new technique for long-term measurement of PAP in conscious unrestrained mice using telemetry.
In five male C57BL/6 mice (B.W. 25-30 g), the sensing catheter of a telemetric transmitter was inserted into the right ventricle and advanced into the pulmonary artery. The transmitter body was positioned either within the abdominal cavity or subcutaneously on the back. During recovery from surgery, mean PAP was recorded daily for 1 week. Subsequently, the PAP responses to acute hypoxia (8% O2 for 10 min) and L-NAME (50 mg/kg, s.c.) were tested in three mice.
By 1-week post surgery, all mice had fully recovered from surgery and baseline MPAP was stable at 14.9+/-0.7 mm Hg. Additionally, the pulmonary vascular stimulants acute hypoxia and L-NAME provoked a 63% and 86% increase MPAP, respectively.
In summary, this study has demonstrated the ability to accurately measure PAP by telemetry in conscious, unrestrained mice. One important application of this technique for future studies is the possibility to assess the relative contribution of specific genes (using 'knock-out' mice) during the chronic development of pulmonary pathological conditions.
基因工程改造特定基因“敲除”小鼠的能力为研究导致肺动脉高压(PAH)发病机制的各种机制提供了强大工具。然而,迄今为止,尚无关于在清醒野生型小鼠中测量肺动脉压(PAP)的报道——这是监测与PAH发病机制相关动态变化的一项基本要求。因此,在本研究中,我们描述了一种使用遥测技术长期测量清醒无束缚小鼠PAP的新技术。
在五只雄性C57BL/6小鼠(体重25 - 30克)中,将遥测发射器的传感导管插入右心室并推进至肺动脉。发射器主体置于腹腔内或背部皮下。在术后恢复期间,每天记录平均PAP,持续1周。随后,在三只小鼠中测试PAP对急性低氧(8% O₂,持续10分钟)和L - 精氨酸甲酯(L - NAME,50毫克/千克,皮下注射)的反应。
术后1周时,所有小鼠均已从手术中完全恢复,基线平均肺动脉压(MPAP)稳定在14.9±0.7毫米汞柱。此外,肺血管刺激剂急性低氧和L - NAME分别使MPAP升高63%和86%。
总之,本研究证明了使用遥测技术在清醒无束缚小鼠中准确测量PAP的能力。该技术在未来研究中的一个重要应用是有可能在肺部病理状况的慢性发展过程中评估特定基因(使用“敲除”小鼠)的相对作用。