Yakubu M A, Leffler C W
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
Pediatr Res. 1997 Mar;41(3):317-20. doi: 10.1203/00006450-199703000-00002.
Subarachnoid hematoma produces cerebral vasoconstriction that may lead to death or permanent disability. After hematoma, enhanced pial arteriolar responses to vasoconstrictor agents have been reported in newborn pigs. The present study was designed to address the hypothesis that 5-hydroxytryptamine (5-HT) constricts piglet pial arterioles, and hematoma augments this constriction. Piglets (1-3 d old) anesthetized with ketamine and acepromazine received either 3 mL of artificial cerebrospinal fluid (control) or autologous nonheparinized blood (hematoma) injected onto the cortical surface. Four days after injection, closed cranial windows were implanted over the injected area under alpha-chloralose anesthesia. Vascular reactivity to 5-HT was examined. In control piglets, topical application of 5-HT (10(-9), 10(-7), and 10(-5) M) induced very mild, dose-dependent constriction of pial arterioles (-6 +/- 1, -10 +/- 2, and -12 +/- 4%, respectively). These constrictions were substantially augmented in piglets with hematoma (-12 +/- 2, -19 +/- 1, and -30 +/- 2%, respectively). After topical application of 5-HT, cerebrospinal fluid samples were collected from under the window to determine the effects of 5-HT on the levels of 6-keto-prostaglandin F1 alpha and thromboxane B2. The baseline levels of 6-keto-prostaglandin F1 alpha and thromboxane B2 before 5-HT were 1791 +/- 387 and 434 +/- 74 pg/mL, respectively, in the control. 5-HT application had no significant effects on these prostanoid levels (levels at the highest concentration of 5-HT had a corresponding value of 1175 +/- 301 and 288 +/- 74 pg/mL for 6-keto-prostaglandin F1 alpha and thromboxane B2, respectively). However, indomethacin (5 mg/kg, i.v.) treatment of the control piglets potentiated the constriction in response to 5-HT (-11 +/- 1, -15 +/- 2, and -24 +/- 3%, respectively) sufficiently to produce constriction similar to that in the hematoma group. 5-HT has little effect on normal pial arterioles of newborn piglets but is a more potent cerebral vasoconstrictor in conjunction with cerebral hematoma.
蛛网膜下腔出血会导致脑血管收缩，这可能会导致死亡或永久性残疾。在新生猪中，出血后已报道软脑膜小动脉对血管收缩剂的反应增强。本研究旨在验证5-羟色胺（5-HT）会使仔猪软脑膜小动脉收缩，且血肿会增强这种收缩的假说。用氯胺酮和乙酰丙嗪麻醉的1至3日龄仔猪，在其皮质表面注射3毫升人工脑脊液（对照组）或自体未肝素化血液（血肿组）。注射4天后，在α-氯醛糖麻醉下，于注射区域植入封闭的颅骨视窗。检测血管对5-HT的反应性。在对照仔猪中，局部应用5-HT（10⁻⁹、10⁻⁷和10⁻⁵ M）引起软脑膜小动脉非常轻微的、剂量依赖性收缩（分别为-6±1、-10±2和-12±4%）。在有血肿的仔猪中，这些收缩显著增强（分别为-12±2、-19±1和-30±2%）。局部应用5-HT后，从视窗下采集脑脊液样本，以确定5-HT对6-酮-前列腺素F1α和血栓素B2水平的影响。在对照组中，如果不应用5-HT，6-酮-前列腺素F1α和血栓素B2的基线水平分别为1791±387和434±74 pg/mL。应用5-HT对这些前列腺素水平无显著影响（在5-HT最高浓度时，6-酮-前列腺素F1α和血栓素B2的相应值分别为1175±301和288±74 pg/mL）。然而，对对照仔猪静脉注射吲哚美辛（5 mg/kg）可增强对5-HT的收缩反应（分别为-11±1、-15±2和-24±3%），足以产生与血肿组相似的收缩。5-HT对新生仔猪正常的软脑膜小动脉影响较小，但与脑血肿一起时是一种更强效的脑血管收缩剂。
