Greene Adrianne N, Clapp Shannon L, Alper Richard H
Pfizer Inc., Drug Safety Research and Development, Safety Pharmacology, Eastern Point Rd, MS 8274-1303, Groton, CT 06340, United States.
J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):218-22. doi: 10.1016/j.vascn.2007.04.006. Epub 2007 May 24.
Rats are used in drug safety because they satisfy regulatory guidelines, there is a large historical database, and their cardiovascular systems respond similarly to humans. The use of radiotelemetry offers a variety of advantages over non-invasive techniques. Implantation of telemetry devices for cardiovascular assessments in rats is not novel, but the time to recover from the surgery has not been reported. In order to assess this, mean arterial blood pressure (MAP), heart rate (HR), body temperature (BT), body weight (BW), food consumption (FC), activity, and general health were determined in male Sprague-Dawley rats for 2 weeks following surgery.
Radiotelemetry transmitters (TL11M2-C50-PXT, Data Sciences International, St. Paul, MN) were implanted into the peritoneal cavity of 15 rats under isoflurane anesthesia; 11 rats were used in the study. Data were collected (500 Hz for 24 h) using PONEMAH Physiology Platform software (Gould Instruments, Inc, Valley View, OH, version 4.0) on days 3, 8 and 15 following surgery. Body weight and 24-h food consumption were recorded 1 day prior to surgery and on days 3, 8 and 15 post-surgery; general health was recorded daily.
MAP tended to be greater on day 3 (104+/-2 mmHg) than on days 8 or 15 (99+/-2 mmHg and 99+/-2 mmHg, respectively). By contrast, activity (arbitrary units) tended to be lower on day 3 (1.9+/-0.2) than on days 8 or 15 (2.9+/-1.2 and 3.0+/-1.0, respectively). HR ( approximately 460 bpm) and BT ( approximately 37.5 degrees C) remained constant throughout the study. FC on day 4 postsurgery was less than pre-surgery (16.7+/-6.6 g vs. 23.6+/-1.2 g) and returned by day 9 (23.6+/-5.4 g). BW on day 4 (295+/-20 g) was not different from presurgery (297+/-11 g) and the rats gained weight on subsequent days. There were no effects on overall appearance and behavior due to surgery.
It is concluded that male Sprague-Dawley rats recover from surgery and can be used approximately 1 week following intraperitoneal implantation of radiotelemetry transmitters with monitoring of body weight and food consumption.
大鼠被用于药物安全性研究，因为它们符合监管指南，有大量的历史数据库，并且其心血管系统对人类的反应相似。与非侵入性技术相比，使用无线电遥测技术具有多种优势。在大鼠中植入用于心血管评估的遥测设备并非新鲜事，但手术恢复时间尚未见报道。为了评估这一点，在雄性斯普拉格-道利大鼠手术后2周内，测定其平均动脉血压（MAP）、心率（HR）、体温（BT）、体重（BW）、食物消耗量（FC）、活动量和总体健康状况。
在异氟烷麻醉下，将无线电遥测发射器（TL11M2-C50-PXT，Data Sciences International，圣保罗，明尼苏达州）植入15只大鼠的腹腔；11只大鼠用于该研究。在手术后第3天、第8天和第15天，使用PONEMAH生理平台软件（Gould Instruments，Inc，山谷景，俄亥俄州，版本4.0）收集数据（500 Hz，持续24小时）。在手术前1天以及手术后第3天、第8天和第15天记录体重和24小时食物消耗量；每天记录总体健康状况。
第3天的MAP（104±2 mmHg）往往高于第8天或第15天（分别为99±2 mmHg和99±2 mmHg）。相比之下，第3天的活动量（任意单位）（1.9±0.2）往往低于第8天或第15天（分别为2.9±1.2和3.0±1.0）。在整个研究过程中，HR（约460次/分钟）和BT（约37.5℃）保持恒定。手术后第4天的FC低于手术前（16.7±6.6克对23.6±1.2克），并在第9天恢复（23.6±5.4克）。第4天的BW（295±20克）与手术前（297±11克）无差异，大鼠在随后几天体重增加。手术对整体外观和行为没有影响。
得出的结论是，雄性斯普拉格-道利大鼠手术后恢复，在腹腔内植入无线电遥测发射器并监测体重和食物消耗量后，大约1周即可使用。
