Karlsten R, Kristensen J D, Gordh T
Department of Anesthesiology, University Hospital, Uppsala, Sweden.
Anesth Analg. 1992 Dec;75(6):972-6. doi: 10.1213/00000539-199212000-00016.
The A1-adenosine receptor agonist, R-phenylisopropyl-adenosine (R-PIA), demonstrated antinociceptive properties in animal studies after intrathecal administration. In the evaluation of a drug for possible spinal injection in humans, the effects of intrathecal R-PIA on spinal cord blood flow (SCBF) were investigated using the laser-Doppler flow-metry technique in anesthetized rats. In low doses (0.1-1 nmol), no change in SCBF was recorded, whereas larger doses (10-100 nmol) caused a significant increase in SCBF. No change in systemic arterial blood pressure could be seen, except for a decrease after administration of the largest dose of R-PIA (100 nmol). It is concluded that R-PIA in doses of 10 nmol and larger induces an increase in SCBF after intrathecal injection in anesthetized rats and that an increase in blood flow is seen before any effect on the systemic circulation is detected. It can also be deduced that the antinociceptive effects of R-PIA after intrathecal injection are not a consequence of spinal ischemia and that disturbances in local blood flow cannot be expected to constitute a neurotoxic factor.
A1 - 腺苷受体激动剂R - 苯基异丙基腺苷(R - PIA)在鞘内给药后的动物研究中显示出抗伤害感受特性。在评估一种可能用于人体脊髓注射的药物时,在麻醉大鼠中使用激光多普勒血流测定技术研究了鞘内注射R - PIA对脊髓血流(SCBF)的影响。低剂量(0.1 - 1 nmol)时,未记录到SCBF的变化,而较大剂量(10 - 100 nmol)则导致SCBF显著增加。除了给予最大剂量的R - PIA(100 nmol)后血压下降外,未观察到体循环动脉血压的变化。得出的结论是,10 nmol及以上剂量的R - PIA在麻醉大鼠鞘内注射后可引起SCBF增加,并且在检测到对体循环有任何影响之前就已出现血流增加。还可以推断,鞘内注射R - PIA后的抗伤害感受作用不是脊髓缺血的结果,并且局部血流紊乱不太可能构成神经毒性因素。