用苯氧苄胺对桡动脉血管进行简短预处理可长期防止血管收缩。
Brief pretreatment of radial artery conduits with phenoxybenzamine prevents vasoconstriction long term.
作者信息
Velez D A, Morris C D, Muraki S, Budde J M, Otto R N, Zhao Z Q, Guyton R A, Vinten-Johansen J
机构信息
Carlyle Fraser Heart Center, Crawford Long Hospital of Emory University, Atlanta, Georgia 30308-2225, USA.
出版信息
Ann Thorac Surg. 2001 Dec;72(6):1977-84. doi: 10.1016/s0003-4975(01)03212-x.
BACKGROUND
Radial artery bypass conduits are prone to early vasospasm or "string sign" with use of vasopressor therapy intraoperatively and postoperatively, causing increased resistance in coronary artery grafts. Current intraoperative treatment with papaverine fails to provide sustained inhibition of vasoconstriction. We tested the hypothesis that a 30-minute pretreatment of radial artery segments with the alpha-adrenergic antagonist phenoxybenzamine (PB) or the putative protein phosphatase 2,3-butadione monoxime (BDM) attenuates vasoconstriction induced by the vasopressors phenylephrine or norepinephrine for as long as 48 hours compared with papaverine.
METHODS
Canine radial arteries were harvested, incubated in control buffer or solutions of papaverine 10(-6) M, BDM 10(-6) M or phenoxybenzamine 10(-6) M for 30 minutes, washed, and stored in drug-free culture medium for 2, 24, or 48 hours. After storage, constriction was induced by norepinephrine at incremental concentrations ranging from 0.7 to 3.5 micromol/L or by phenylephrine (0.300 to 1.5 micromol/L) with or without the inhibitors, and the degree of vasoconstriction was quantified in organ chambers. Responses to norepinephrine or phenylephrine were compared to constriction with receptor-independent potassium chloride KC1 (30 mmol/L).
RESULTS
Maximum responses to phenylephrine and norepinephrine were comparable at 2, 24, and 48 hours after harvest in the control group (phenylephrine: 67% +/- 4%, 62% +/- 6%, 65% +/- 6% of KC1 response; norepinephrine: 75% +/- 4%, 62% +/- 1%, 58% +/- 7%, respectively). Papaverine failed to attenuate constriction to phenylephrine and norepinephrine 2, 24, or 48 hours posttreatment. Pretreatment with BDM did not reduce vasoconstriction responses to phenylephrine or norepinephrine 2 hours after incubation but did reduce constriction responses thereafter. In contrast, phenoxybenzamine completely attenuated constriction to both phenylephrine (19% +/- 8%, 1% +/- 4%, -12% +/- 4%) and norepinephrine (7.1% +/- 1%, -5% +/- 5%, -20% +/- 5%) at 2, 24, and 48 hours posttreatment, respectively. Phenoxybenzamine did not alter endothelial function relative to controls at any time point.
CONCLUSIONS
Thirty-minute pretreatment of RA conduits with 10(-6) M phenoxybenzamine completely inhibits vasoconstriction to phenylephrine and norepinephrine for as long as 48 hours. Soaking radial artery grafts briefly in phenoxybenzamine solution before implantation may be effective in preventing postoperative vasospasm caused by two common alpha-adrenergic agonists used in postoperative hemodynamic management.
背景
桡动脉旁路移植血管在术中及术后使用血管升压药治疗时容易出现早期血管痉挛或“条索征”，导致冠状动脉移植物阻力增加。目前术中使用罂粟碱治疗未能持续抑制血管收缩。我们检验了这样一个假设：与罂粟碱相比，用α-肾上腺素能拮抗剂酚苄明（PB）或假定的蛋白磷酸酶2,3-丁二酮单肟（BDM）对桡动脉段进行30分钟预处理，可减轻去氧肾上腺素或去甲肾上腺素诱导的血管收缩长达48小时。
方法
获取犬的桡动脉，在对照缓冲液或10⁻⁶ M罂粟碱、10⁻⁶ M BDM或10⁻⁶ M酚苄明溶液中孵育30分钟，冲洗后，在无药物的培养基中保存2、24或48小时。保存后，用去甲肾上腺素（浓度从0.7至3.5 μmol/L递增）或去氧肾上腺素（0.300至1.5 μmol/L）诱导收缩，有或无抑制剂，在器官浴槽中对血管收缩程度进行定量。将对去甲肾上腺素或去氧肾上腺素的反应与用非受体依赖性氯化钾（KC1，30 mmol/L）诱导的收缩进行比较。
结果
在收获后2、24和48小时，对照组对去氧肾上腺素和去甲肾上腺素的最大反应相当（去氧肾上腺素：分别为KC1反应的67%±4%、62%±6%、65%±6%；去甲肾上腺素：分别为75%±4%、62%±1%、58%±7%）。罂粟碱在处理后2、24或48小时未能减轻对去氧肾上腺素和去甲肾上腺素的收缩。用BDM预处理在孵育2小时后未降低对去氧肾上腺素或去甲肾上腺素的血管收缩反应，但此后确实降低了收缩反应。相比之下，酚苄明在处理后2、24和48小时分别完全减轻了对去氧肾上腺素（19%±8%、1%±4%、-12%±4%）和去甲肾上腺素（7.1%±1%、-5%±5%、-20%±5%）的收缩。在任何时间点，酚苄明相对于对照组均未改变内皮功能。
结论
用10⁻⁶ M酚苄明对桡动脉移植物进行30分钟预处理可完全抑制对去氧肾上腺素和去甲肾上腺素长达48小时的血管收缩。在植入前将桡动脉移植物短暂浸泡在酚苄明溶液中可能有效预防术后血流动力学管理中常用的两种α-肾上腺素能激动剂引起的术后血管痉挛。
Zotero 插件