Davies M G, Dalen H, Svendsen E, Hagen P O
Vascular Biology and Atherosclerosis Research Laboratory, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Surg Res. 1997 Apr;69(1):14-22. doi: 10.1006/jsre.1997.5019.
The long-term biological characteristics and the functional and morphological changes that occur in fresh allografts are poorly understood. This study tests the hypothesis that the development of intimal hyperplasia and its associated functional changes are accelerated in an allograft compared to an autograft due to the additional immunological stimuli. Common carotid vein bypass grafts were performed in 40 New Zealand White rabbits: 20 received their ipsilateral jugular veins (autologous) and 20 received the fresh contralateral jugular veins from the control rabbit (allogenic). Electron microscopy was performed and intimal and medial dimensions were determined by videoplanimetry at 7, 14, and 28 days. Contraction and relaxation studies to a panel of agonists were also performed. The EC50's (agonist concentration which produces 50% of the maximal response) were calculated. All grafts remained patent. Allografts showed a 51% decrease in overall mean intimal thickness (41 +/- 3 microns vs. 83 +/- 12 microns; P < 0.01) and a 97% increase in overall mean medial thickness (140 +/- 15 microns vs. 71 +/- 3 microns; P < 0.01) compared to the autografts. The lumen of the allogenic vein grafts was equivalent to the autologous vein grafts. Overall mean total wall thickness only increased by 17%, 181 microns vs. 154 microns for allo- and autografts, respectively. The EC50 for norepinephrine, histamine, and bradykinin were similar in the auto- and allografts, while the EC50 to serotonin was significantly less in the allografts than in the autografts. Neither the precontracted auto- or allografts relaxed to acetylcholine or serotonin (receptor mediated, endothelium dependent). The EC50 for calcium ionophore (nonreceptor mediated, endothelium dependent) was equivalent in the auto- and allografts. The EC50 for the sodium nitroprusside-induced relaxation (endothelium independent) was significantly higher in the allograft than in the autograft. This study demonstrates that there are two different vasculopathies occurring in autografts and allografts: intimal hyperplasia is predominant in the autograft while an exaggerated medial response is predominant in the allograft. Serotonin contractility and endothelial-independent relaxation are enhanced in the allograft compared to the autograft.
人们对新鲜同种异体移植物中发生的长期生物学特性以及功能和形态变化了解甚少。本研究检验了以下假设:由于额外的免疫刺激,同种异体移植物中内膜增生的发展及其相关的功能变化比自体移植物更快。对40只新西兰白兔进行了颈总静脉搭桥手术:20只接受其同侧颈静脉(自体),20只接受来自对照兔的新鲜对侧颈静脉(同种异体)。在第7、14和28天进行电子显微镜检查,并通过视频测量法确定内膜和中膜尺寸。还对一组激动剂进行了收缩和舒张研究。计算了EC50(产生最大反应50%的激动剂浓度)。所有移植物均保持通畅。与自体移植物相比,同种异体移植物的总体平均内膜厚度降低了51%(41±3微米对83±12微米;P<0.01),总体平均中膜厚度增加了97%(140±15微米对71±3微米;P<0.01)。同种异体静脉移植物的管腔与自体静脉移植物相当。总体平均总壁厚度仅增加了17%,同种异体移植物和自体移植物分别为181微米和154微米。去甲肾上腺素、组胺和缓激肽的EC50在自体移植物和同种异体移植物中相似,而5-羟色胺的EC50在同种异体移植物中明显低于自体移植物。预收缩的自体或同种异体移植物对乙酰胆碱或5-羟色胺(受体介导、内皮依赖性)均无舒张反应。钙离子载体的EC50(非受体介导、内皮依赖性)在自体移植物和同种异体移植物中相当。硝普钠诱导的舒张反应(内皮非依赖性)的EC50在同种异体移植物中明显高于自体移植物。本研究表明,自体移植物和同种异体移植物中存在两种不同的血管病变:自体移植物中内膜增生为主,而同种异体移植物中中膜反应过度为主。与自体移植物相比,同种异体移植物中5-羟色胺收缩性和内皮非依赖性舒张增强。