McMahon Carrie, Mitchell Andrea Z, Klein Jessica L, Jenkins Angela C, Sarazan R Dustan
Covance Laboratories Inc., 3301 Kinsman Boulevard, Madison, WI 53704-2595, USA.
J Pharmacol Toxicol Methods. 2010 Sep-Oct;62(2):127-35. doi: 10.1016/j.vascn.2010.05.018. Epub 2010 Jun 15.
Current techniques used to accurately determine arterial blood pressure (BP) in conscious, unrestrained monkeys require invasive telemetry. This study evaluated the functionality of an implanted miniature telemetry blood pressure transmitter for the collection of BP measurements in conjunction with electrocardiographic measurements using a jacketed external telemetry (JET) system in conscious, unrestrained cynomolgus monkeys.
Twenty-four animals were surgically implanted with the transmitter in the right femoral artery. Local tolerability to the implant, signal quality, and variability in hemodynamic values were evaluated. On alternate weeks, animals were given single doses of positive control agents to produce hypotensive (clonidine hydrochloride) or hypertensive (L-NAME) effects. Undisturbed telemetry BP data were continuously collected for at least 24h following dosing and analyzed.
While exhibiting remarkably high signal quality ( approximately 95% data points retained over 24h of data collection) and moderate variability across study weeks in baseline pulse height measurements (changes as small as < 0 mmHg), nine of 18 transmitters were nonfunctional by 19 weeks post-surgery, most likely due to migration of the catheter out of the artery. In animals given positive control agents, L-NAME induced a statistically significant increase (> or = + 8 mmHg) and clonidine hydrochloride induced a statistically significant decrease (-11 mmHg) in mean arterial pressures. Histological analysis revealed femoral arterial thickening near the sites of implantation.
These results demonstrate the ability of the miniature BP transmitter, in conjunction with the JET system, to detect small changes in hemodynamic data continuously collected in conscious unrestrained monkeys. Future optimization of the transmitter includes the addition of a suture rib to the transmitter body and increased catheter size to prevent catheter migration out of the artery, the root cause of failed transmitters. The miniature blood pressure transmitter evaluated provides a minimally invasive technique for continuous collection of hemodynamic data in a toxicology study environment.
目前用于准确测定清醒、不受束缚的猴子动脉血压(BP)的技术需要进行侵入性遥测。本研究评估了一种植入式微型遥测血压变送器的功能,该变送器与一种带套外置遥测(JET)系统相结合,用于在清醒、不受束缚的食蟹猴中收集血压测量值,并同时进行心电图测量。
24只动物通过手术将变送器植入右股动脉。评估了对植入物的局部耐受性、信号质量以及血流动力学值的变异性。每隔一周,给动物单次注射阳性对照剂以产生降压(盐酸可乐定)或升压(L-精氨酸甲酯)作用。给药后连续至少24小时不间断地收集遥测血压数据并进行分析。
虽然显示出非常高的信号质量(在24小时数据收集过程中约95%的数据点得以保留),且在基线脉搏高度测量中跨研究周的变异性适中(变化小至<0 mmHg),但18个变送器中有9个在手术后19周时失去功能,最可能的原因是导管从动脉中移位。在给予阳性对照剂的动物中,L-精氨酸甲酯使平均动脉压出现统计学上的显著升高(≥+8 mmHg),盐酸可乐定使平均动脉压出现统计学上的显著降低(-11 mmHg)。组织学分析显示植入部位附近的股动脉增厚。
这些结果表明,微型血压变送器与JET系统相结合,能够检测在清醒不受束缚的猴子中连续收集的血流动力学数据的微小变化。变送器未来的优化包括在变送器主体上增加缝合肋以及增大导管尺寸,以防止导管从动脉中移位,这是变送器失效的根本原因。所评估的微型血压变送器为在毒理学研究环境中连续收集血流动力学数据提供了一种微创技术。