Létienne Robert, Verscheure Yvan, John Gareth W
Centre de Recherche Pierre Fabre, Castres, France.
J Pharmacol Exp Ther. 2003 Oct;307(1):168-74. doi: 10.1124/jpet.103.054940. Epub 2003 Sep 3.
The effects of naratriptan, rizatriptan, and sumatriptan on arteriovenous oxygen saturation difference and carotid hemodynamics were compared in the anesthetized pig. Oxygen and carbon dioxide partial pressures in systemic arterial and jugular venous blood as well as hemoglobin oxygen saturation were determined by conventional blood gas analysis. Vehicle (n = 19) or naratriptan, rizatriptan, or sumatriptan (0.63, 2.5, 10, 40, 160, 630, and 2,500 microg/kg i.v.; n = 7/group) were infused cumulatively. In naratriptan-, rizatriptan-, and sumatriptan-treated animals, jugular venous oxygen saturation decreased dose dependently (geometric mean ED50 values of 3.1, 17.9, and 16.0 microg/kg, respectively) concomitantly with increases in carotid vascular resistance. Rizatriptan significantly and dose dependently, from 160 microg/kg, increased PvCO2 (P < 0.05 versus vehicle). Naratriptan and sumatriptan also tended to increase PvCO2 albeit nonstatistically significantly. All three triptans consistently evoked quantitatively similar carotid vasoconstriction, whereas decreases in jugular venous oxygen saturation (VOS) and increases in PvCO2 had different magnitudes and occurred only in around one-half of the animals studied. Maximal variations in PvCO2 were found to correlate highly with those in PvO2 (P = 0.002), but maximal variations in carotid resistance failed to correlate with those in PvCO2 (P = 0.76) or PvO2 (P = 0.28). The results demonstrate that the triptans investigated robustly produced carotid vasoconstriction, but elicited less consistent decreases in VOS and increases in jugular PvCO2, possibly suggestive of distinct mechanisms. Collectively, the data suggest that triptan-induced increases in arteriovenous oxygen saturation difference and carbon dioxide partial pressure in venous blood draining the head are class effects.
在麻醉猪中比较了那拉曲普坦、利扎曲普坦和舒马曲坦对动静脉血氧饱和度差和颈动脉血流动力学的影响。通过常规血气分析测定全身动脉血和颈静脉血中的氧分压、二氧化碳分压以及血红蛋白氧饱和度。累积输注溶媒（n = 19）或那拉曲普坦、利扎曲普坦或舒马曲坦（静脉注射剂量为0.63、2.5、10、40、160、630和2500μg/kg；每组n = 7）。在接受那拉曲普坦、利扎曲普坦和舒马曲坦治疗的动物中，颈静脉血氧饱和度呈剂量依赖性降低（几何平均ED50值分别为3.1、17.9和16.0μg/kg），同时颈动脉血管阻力增加。从160μg/kg起，利扎曲普坦显著且呈剂量依赖性地增加颈静脉二氧化碳分压（与溶媒相比，P < 0.05）。那拉曲普坦和舒马曲坦也有增加颈静脉二氧化碳分压的趋势，尽管无统计学意义。所有三种曲坦类药物均一致引起数量上相似的颈动脉血管收缩，而颈静脉血氧饱和度（VOS）降低和颈静脉二氧化碳分压升高的程度不同，且仅在约一半的研究动物中出现。发现颈静脉二氧化碳分压的最大变化与颈静脉氧分压的最大变化高度相关（P = 0.002），但颈动脉阻力的最大变化与颈静脉二氧化碳分压（P = 0.76）或颈静脉氧分压（P = 0.28）的变化无相关性。结果表明，所研究的曲坦类药物均有力地引起颈动脉血管收缩，但引起的VOS降低和颈静脉二氧化碳分压升高不太一致，这可能提示存在不同的机制。总体而言，数据表明曲坦类药物引起的动静脉血氧饱和度差增加和引流头部的静脉血中二氧化碳分压升高是类效应。
