Bordet R, Verwaerde P, Tran M A, Marques M A, Montastruc J L, Senard J M
Service de Pharmacologie Hospitalière, Centre Hospitalier Universitaire de Lille, France.
Fundam Clin Pharmacol. 1997;11(3):237-44. doi: 10.1111/j.1472-8206.1997.tb00191.x.
This paper investigates the effects of octreotide (0.1 mg/kg, subcutaneous) on cardiovascular adaptation during head-up tilt test in an experimental model of neurogenic orthostatic hypotension (OH) obtained by chronic sinoaortic denervation in anaesthetized dogs. Blood pressure (BP), heart rate (HR), spectral variability (Fast Fourier transformation on 512 consecutive points, delta t: 2 Hz) and plasma catecholamine levels were measured in a double blind cross-over randomized study versus placebo, in supine position and during a head-up tilt test (80 degrees, 10 min) in six sinoaortic denervated and six control (normal) dogs. In normal dogs, head-up tilt test significantly increased HR and diastolic blood pressure (DBP). Plasma noradrenaline levels and energy of the low frequency band (40-150 mHz) of systolic blood pressure (SBP) significantly increased whereas the energy of the low frequency band of HR significantly decreased. Placebo and octreotide failed to modify supine and head-up tilt values of the measured parameters (except the value of low frequency band of SBP, which increased after octreotide). In sinoaortic denervated dogs, supine values of BP, HR and plasma noradrenaline levels were significantly higher than in controls whereas the energy of the low frequency spectral band of HR and SBP was similar to controls. Head-up tilt test induced a dramatic decrease in BP. HR, plasma noradrenaline levels and energy of the low frequency band of SBP and HR remained unchanged during head-up tilt tests. Neither supine nor head-up tilt values of these parameters were modified 45 min after octreotide or placebo administration. These results show that sinoaortic denervation is a reproducible model of OH characterized by a lack of activation of sympathetic efferent pathways during head-up tilt tests. Octreotide at the dose used remains ineffective to prevent the fall in BP under these experimental conditions.
本文研究了奥曲肽（0.1毫克/千克，皮下注射）对麻醉犬慢性去窦主动脉神经支配所致神经源性直立性低血压（OH）实验模型在头高位倾斜试验期间心血管适应性的影响。在一项双盲交叉随机研究中，对6只去窦主动脉神经支配犬和6只对照（正常）犬测量了仰卧位和头高位倾斜试验（80度，10分钟）期间的血压（BP）、心率（HR）、频谱变异性（对512个连续点进行快速傅里叶变换，δt：2赫兹）和血浆儿茶酚胺水平，与安慰剂进行对比。在正常犬中，头高位倾斜试验显著增加了HR和舒张压（DBP）。血浆去甲肾上腺素水平以及收缩压（SBP）低频带（40 - 150毫赫兹）的能量显著增加，而HR低频带的能量显著降低。安慰剂和奥曲肽未能改变所测参数的仰卧位和头高位倾斜值（除SBP低频带的值在奥曲肽后增加）。在去窦主动脉神经支配犬中，BP、HR和血浆去甲肾上腺素水平的仰卧位值显著高于对照组，而HR和SBP低频谱带的能量与对照组相似。头高位倾斜试验导致BP急剧下降。在头高位倾斜试验期间，HR、血浆去甲肾上腺素水平以及SBP和HR低频带的能量保持不变。奥曲肽或安慰剂给药45分钟后，这些参数的仰卧位和头高位倾斜值均未改变。这些结果表明，去窦主动脉神经支配是OH的一种可重复模型，其特征是在头高位倾斜试验期间交感传出通路缺乏激活。在这些实验条件下，所用剂量的奥曲肽仍无法有效预防BP下降。
