Meyer Olivier, Jenni Roland, Greiter-Wilke Andrea, Breidenbach Alexander, Holzgrefe Henry H
F Hoffmann-La Roche, Pharmaceuticals Division Non-Clinical Drug Safety, Basel, Switzerland.
J Am Assoc Lab Anim Sci. 2010 Jul;49(4):464-71.
This study compared torcetrapib-induced blood pressure (BP) changes simultaneously obtained by high-definition oscillometry (HDO) and telemetry. Male beagles (n = 6) received single oral doses of vehicle or torcetrapib at 10 or 30 mg/kg; BP were acquired simultaneously by HDO and telemetry from 2 h before dosage until 7 h afterward. Systolic, diastolic, and mean arterial pressures (MAP) and heart rate were compared by using Altman-Bland agreement analysis. Dogs were allocated into subgroups according to temperament and baseline MAP (less than 110 mm Hg and 110 mm Hg or greater). Both methods demonstrated high precision. HDO recordings exhibited higher variability for all parameters (inclusive MAP SDs were 7.0 +/- 2.7 mm Hg for HDO compared with 3.4 +/- 1.9 mm Hg for telemetry), accompanied by a positive bias for all pressures (systolic, 10.4 mm Hg; diastolic, 5.7 mm Hg; MAP, 1.9 mm Hg). Both methods detected similar maximal increases in MAP with 30 mg/kg torcetrapib (HDO, 15.8 +/- 10.4 mm Hg; telemetry, 15.8 +/- 5.3 mm Hg). No significant effects were noted for heart rate. Torcetrapib elicited a dose-dependent increase in BP in dogs with baseline MAP of less than 110 mm Hg, whereas increases were maximal with 10 mg/kg in the other group, and dose-dependence was no longer observed. BP changes were influenced by animal temperament, demonstrating that HDO results must be interpreted with caution. HDO may provide a useful and accurate method for noninvasive BP measurements in canine studies.
本研究比较了通过高清示波法(HDO)和遥测技术同时获得的托彻普贝引起的血压(BP)变化。雄性比格犬(n = 6)接受单次口服赋形剂或10或30 mg/kg的托彻普贝;在给药前2小时至给药后7小时通过HDO和遥测技术同时采集血压。使用奥特曼-布兰德一致性分析比较收缩压、舒张压和平均动脉压(MAP)以及心率。根据气质和基线MAP(小于110 mmHg和110 mmHg或更高)将犬分为亚组。两种方法均显示出高精度。HDO记录的所有参数变异性更高(HDO的MAP标准差为7.0±2.7 mmHg,而遥测技术为3.4±1.9 mmHg),所有压力均存在正偏差(收缩压为10.4 mmHg;舒张压为5.7 mmHg;MAP为1.9 mmHg)。两种方法检测到30 mg/kg托彻普贝引起的MAP最大升高相似(HDO为15.8±10.4 mmHg;遥测技术为15.8±5.3 mmHg)。未观察到对心率有显著影响。托彻普贝在基线MAP小于110 mmHg的犬中引起剂量依赖性血压升高,而在另一组中10 mg/kg时升高最大,且不再观察到剂量依赖性。血压变化受动物气质影响,表明必须谨慎解释HDO结果。HDO可能为犬类研究中的无创血压测量提供一种有用且准确的方法。