Kern C, Mautz D S, Bernards C M
Department of Anesthesiology, University of Washington, Seattle 98195, USA.
Anesthesiology. 1995 Nov;83(5):1078-81. doi: 10.1097/00000542-199511000-00021.
Epinephrine commonly is added to epidural opioids and local anesthetics, however, little is known about the fate of epidurally administered epinephrine. Studies have identified the epinephrine metabolizing enzyme, catechol-O-methyl transferase (COMT), in the cranial meninges of several species. The purpose of this study was to determine whether the spinal meninges also contain COMT and are capable of metabolizing epinephrine. If so, then the spinal meninges may have an important impact in limiting the bioavailability of epinephrine in both the spinal cord and epidural space.
Spinal meningeal specimens measuring 4 cm2 were obtained from monkeys (M. nemestrina) and farm-bred pigs and were incubated in bicarbonate-buffered mock cerebrospinal fluid. Epinephrine (200 micrograms base) was added at t = 0, and 200 min later, the mock cerebrospinal fluid was collected for metanephrine analysis. In separate experiments, pig meningeal specimens were separated into dura mater, pia-arachnoid mater, and pia mater, and the experiments were repeated to determine which meninx had the greatest COMT activity.
Metanephrine was produced by monkey meninges at the rate of 0.47 ng.min-1.cm-2 and by pig meninges at the rate of 0.23 ng.min-1.cm-2 (P > 0.05). The pia-arachnoid meninx produced metanephrine at a greater rate (4.48 +/- 0.46 ng.min-1.mg-1 tissue) than did the pia mater (1.3 +/- 0.15 ng.min-1.mg-1 tissue) or dura mater alone (1.82 +/- 0.23 ng.min-1.mg-1 tissue).
These data demonstrate the functional presence of COMT in the spinal meninges of pigs and monkeys and suggest that the spinal meninges may limit the spinal bioavailability of epidurally or intrathecally administered epinephrine.
肾上腺素通常会添加到硬膜外阿片类药物和局部麻醉剂中,然而,关于硬膜外给药肾上腺素的转归知之甚少。研究已在几种物种的颅膜中鉴定出肾上腺素代谢酶——儿茶酚 - O - 甲基转移酶(COMT)。本研究的目的是确定脊髓膜中是否也含有COMT并能够代谢肾上腺素。如果是这样,那么脊髓膜可能在限制肾上腺素在脊髓和硬膜外间隙的生物利用度方面具有重要影响。
从恒河猴(食蟹猴)和农场饲养的猪获取面积为4平方厘米的脊髓膜标本,并在碳酸氢盐缓冲的模拟脑脊液中孵育。在t = 0时加入肾上腺素(200微克碱),200分钟后,收集模拟脑脊液进行间甲肾上腺素分析。在单独的实验中,将猪的脑膜标本分离为硬脑膜、软脑膜 - 蛛网膜和软脑膜,并重复实验以确定哪个脑膜具有最大的COMT活性。
间甲肾上腺素由猴脑膜以0.47纳克·分钟⁻¹·厘米⁻²的速率产生,由猪脑膜以0.23纳克·分钟⁻¹·厘米⁻²的速率产生(P>0.05)。软脑膜 - 蛛网膜产生间甲肾上腺素的速率(4.48±0.46纳克·分钟⁻¹·毫克⁻¹组织)高于软脑膜(1.3±0.15纳克·分钟⁻¹·毫克⁻¹组织)或单独的硬脑膜(1.82±0.23纳克·分钟⁻¹·毫克⁻¹组织)。
这些数据证明了COMT在猪和猴的脊髓膜中功能性存在,并表明脊髓膜可能会限制硬膜外或鞘内注射肾上腺素的脊髓生物利用度。