Mueed Irem, Tazzeo Tracy, Liu Ciaqiong, Pertens Evi, Zhang Yongde, Cybulski Irene, Semelhago Lloyd, Noora Joseph, Lamy Andre, Teoh Kevin, Chu Victor, Janssen Luke J
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
J Thorac Cardiovasc Surg. 2008 Jan;135(1):131-8. doi: 10.1016/j.jtcvs.2007.06.023.
Radial artery vasospasm remains a potential cause of early graft failure after coronary bypass graft surgery, despite pretreatment with alpha-adrenergic or calcium channel blockers. We examined the roles of isoprostanes and prostanoid receptors selective for thromboxane A2 in the vasoconstriction of human radial arteries.
Human radial arterial segments were pretreated intraoperatively with verapamil/papaverine or nitroglycerine/phenoxybenzamine, or not treated. In the laboratory, we measured isometric contractions in ring segments, vasoconstriction in pressurized segments, and changes in [Ca2+] and K+ currents in single cells.
Although phenoxybenzamine eliminated adrenergic responses, the isoprostane 15-F(2t)-IsoP and 2 closely related E-ring molecules (15-E(1t)-IsoP and 15-E(2t)-IsoP) still evoked powerful contractions; 15-E(2t)-IsoP was approximately 10-fold more potent than the other 2 agents. Responses were mediated through thromboxane receptors because they were sensitive to ICI-192605. Furthermore, they were sensitive to the Rho-kinase inhibitors Y-27632 or H-1152 (both 10(-5) mol/L) or to cyclopiazonic acid (which depletes the internal Ca2+ pool), but not to nifedipine. In single cells, 15-E(2t)-IsoP elevated [Ca2+]i and suppressed K+ current.
Isoprostanes accumulate after coronary artery bypass graft surgery, yet none of the currently available antispasm treatments for radial artery grafts is effective against isoprostane-induced vasoconstriction. It is imperative that more specific treatment strategies be developed. We found that isoprostane responses in radial arteries are mediated by prostanoid receptors selective for thromboxane A2 with activation of Rho-kinase and release of Ca2+. Pretreatment of radial artery grafts with Rho-associated kinase inhibitors may potentially reduce postoperative graft spasm. Clinical studies to test this are indicated.
尽管术前使用了α-肾上腺素能阻滞剂或钙通道阻滞剂，但桡动脉痉挛仍是冠状动脉搭桥术后早期移植物功能衰竭的一个潜在原因。我们研究了异前列腺素和对血栓素A2有选择性的前列腺素受体在人桡动脉血管收缩中的作用。
人桡动脉节段在术中用维拉帕米/罂粟碱或硝酸甘油/酚苄明预处理，或不进行处理。在实验室中，我们测量了环段的等长收缩、加压段的血管收缩以及单细胞中[Ca2+]和K+电流的变化。
尽管酚苄明消除了肾上腺素能反应，但异前列腺素15-F(2t)-IsoP和2个密切相关的E环分子（15-E(1t)-IsoP和15-E(2t)-IsoP）仍能引起强烈收缩；15-E(2t)-IsoP的效力比其他2种物质强约10倍。这些反应是通过血栓素受体介导的，因为它们对ICI-192605敏感。此外，它们对Rho激酶抑制剂Y-27632或H-1152（均为10(-5)mol/L）或对环匹阿尼酸（耗尽细胞内Ca2+池）敏感，但对硝苯地平不敏感。在单细胞中，15-E(2t)-IsoP升高了[Ca2+]i并抑制了K+电流。
冠状动脉搭桥术后异前列腺素会蓄积，但目前用于桡动脉移植物的抗痉挛治疗方法均对异前列腺素诱导的血管收缩无效。必须制定更具特异性的治疗策略。我们发现桡动脉中的异前列腺素反应是由对血栓素A2有选择性的前列腺素受体介导的，伴有Rho激酶的激活和Ca2+的释放。用Rho相关激酶抑制剂预处理桡动脉移植物可能会降低术后移植物痉挛。有必要进行临床研究来验证这一点。
