Mussa Shafi, Prior Tash, Alp Nicholas, Wood Kathryn, Channon Keith M, Taggart David P
Department of Cardiothoracic Surgery, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK.
Eur J Cardiothorac Surg. 2004 Nov;26(5):988-94. doi: 10.1016/j.ejcts.2004.06.018.
Radial arteries are increasingly used as conduits for coronary artery bypass grafts, but perioperative graft vasospasm remains a concern. In vitro testing has demonstrated the efficacy of phenoxybenzamine and verapamil/nitroglycerin as topical antispasmodic agents, but their duration of action in vivo is unknown. Using an in vivo mouse model, we measured their duration of action in functioning vascular grafts, and compared this to their in vitro duration of action in ungrafted vascular segments.
Two millimetre mouse aortic segments (C57/BL6) were incubated with phenoxybenzamine, verapamil/nitroglycerin, or buffer (controls) for 15 min in organ chambers. Isometric tension responses to phenylephrine and prostaglandin F2alpha were measured at 0, 2, 6 and 12 h post-incubation. In parallel, 36 murine infrarenal aortic interposition grafts (2 mm) were performed. Twelve grafts were pre-treated (15 min) with phenoxybenzamine, 12 with verapamil/nitroglycerin and 12 remained untreated (controls). Isometric tension responses to the same agonists were measured in grafts harvested 2, 6, 13 and 23 h after surgery.
Phenoxybenzamine prevented alpha-adrenergic vasoconstriction for up to 16 h in vivo (grafts), and 12h in vitro (ungrafted segments). Verapamil/nitroglycerin was effective for at least 2 h in vitro, but did not prevent vasoconstriction after 2 h in vivo.
The mouse model appears to be a useful technique for assessing the pharmacological properties of antispasmodic agents in vivo. Phenoxybenzamine has an extended action in arterial grafts in vivo. Verapamil/nitroglycerin is short-lived in vivo but lasts longer in vitro. Measurements of antispasmodic duration of action in vitro should be interpreted with caution.
桡动脉越来越多地被用作冠状动脉旁路移植术的血管 conduit，但围手术期移植血管痉挛仍然是一个问题。体外试验已证明酚苄明以及维拉帕米/硝酸甘油作为局部抗痉挛药物的有效性，但其体内作用持续时间尚不清楚。我们使用体内小鼠模型，测量它们在功能性血管移植物中的作用持续时间，并将其与在未移植血管段中的体外作用持续时间进行比较。
将两毫米的小鼠主动脉段（C57/BL6）在器官腔中与酚苄明、维拉帕米/硝酸甘油或缓冲液（对照）孵育15分钟。在孵育后0、2、6和12小时测量对去氧肾上腺素和前列腺素F2α的等长张力反应。同时，进行36例小鼠肾下腹主动脉间置移植术（2毫米）。12个移植物用酚苄明预处理（15分钟），12个用维拉帕米/硝酸甘油预处理，12个未处理（对照）。在术后2、6、13和23小时采集的移植物中测量对相同激动剂的等长张力反应。
酚苄明在体内（移植物）可预防α-肾上腺素能血管收缩长达16小时，在体外（未移植段）为12小时。维拉帕米/硝酸甘油在体外至少有效2小时，但在体内2小时后不能预防血管收缩。
小鼠模型似乎是评估体内抗痉挛药物药理学特性的一种有用技术。酚苄明在体内动脉移植物中作用时间延长。维拉帕米/硝酸甘油在体内作用时间短，但在体外持续时间更长。体外抗痉挛作用持续时间的测量应谨慎解释。
