兔颈动脉旁路移植术后移植静脉血栓形成情况观察

目的观察兔颈动脉旁路移植术后移植静脉血栓形成情况。方法构建30例兔颈动脉旁路移植模型,术后不用抗凝药物。术后当天,对移植静脉行血管彩色多普勒检查;术后3d取移植静脉,手术显微镜下观察移植静脉血栓形成情况。结果术后当天,超声检查示移植静脉均通畅;术后3d,30条移植静脉中有血栓形成者22条,血栓均发生在移植静脉中间段。结论兔颈动脉旁路移植术后移植静脉血栓形成率高,多发在静脉中间段。     

中国常用动脉化冠状动脉旁路移植术的通畅率及疗效

目前冠状动脉旁路移植术通常采用一支乳内动脉加一支或多支大隐静脉作为桥血管,大隐静脉会逐渐粥样硬化而闭塞,动脉的通畅率远高于大隐静脉。左乳内动脉已常规应用于冠状动脉旁路移植术,同应用双侧乳内动脉相比,左乳内动脉加大隐静脉被认为是远期死亡、心脏事件的独立危险因素。乳内动脉用于左侧冠状动脉时通畅率一样;原位或复合桥移植时所有的乳内动脉通畅率相同,但吻合于主动脉时通畅率降低,所以原位乳内动脉通畅率高于游离乳内动脉。胃网膜右动脉和桡动脉宜吻合于近端狭窄严重者。双侧乳内动脉+胃网膜右动脉可避免触及主动脉,最大程度地减少脑部并发症的发生。70岁以下冠状动脉旁路移植术、预期寿命5年以上者,应选择双侧乳内动脉;60岁以下没有或很少合并症的冠状动脉旁路移植术患者可考虑全动脉化搭桥手术。     

冠状动脉旁路移植术静脉移植物内膜增生的治疗策略

尽管冠状动脉旁路移植术中动脉桥血管被广泛使用且远期通畅率高,但大隐静脉移植物仍是冠状动脉旁路移植术使用最多的桥血管,而大隐静脉移植物术后10年通畅率大约60%。静脉移植物再狭窄的机制包括血栓形成、心内膜增生和粥样硬化等。防治静脉移植物再狭窄的方案包括药物治疗、基因治疗和血管外支架。现就上述治疗方案作一综述。     

冠状动脉旁路移植血管的生物学特性研究进展

目前临床上常用的血管桥有乳内动脉、桡动脉和大隐静脉,3种桥血管不同的组织结构、对血管活性物质不同的反应性和血管壁平滑肌受体分布的不同,与移植血管痉挛的发生率及近远期通畅率密切相关,是关系到冠状动脉旁路移植术手术成败的重要因素之一。对桥血管结构、功能的了解,有助于临床合理选择和应用合适的移植血管,为提高冠状动脉旁路移植术的近远期通畅率提供一定的理论依据现综述如下。     

移植静脉外膜增生与兔血管再狭窄的相关性

目的 探讨冠状动脉旁路移植术后移植静脉外膜增生与血管再狭窄的相关性.方法 构建20例兔颈动脉旁路移植模型,术后当日行血管彩色多普勒检查,检测移植静脉的通畅性.术后30 d,取出移植静脉,组织病理标本切片、HE染色,测量外膜面积和管腔面积.用统计软件分析外膜面积与管腔面积的相关性.结果 术后当日,血管多普勒证明,所有20例模型移植静脉全部通畅.统计软件分析结果显示,移植静脉外膜面积与管腔面积成直线关系.结论 移植静脉外膜增生与血管管腔再狭窄有相关性.移植静脉外膜增生越重,管腔越狭窄.     

自噬相关基因5下调抑制静脉桥血管狭窄

目的探讨自噬相关基因5(Atg5)在小鼠下腔静脉移植术后静脉桥血管狭窄过程中的作用。方法30只雄性C57BL/6小鼠及20只Atg5^+/-小鼠分为WT假手术组(10只),WT手术组(受体10只,供体10只),Atg5^+/-手术组(受体10只,供体10只)。复制小鼠下腔静脉移植模型。HE染色观察下腔静脉管腔面积,Real-time PCR检测下腔静脉组织中Atg5、LC3 mRNA表达;Westem-Blot检测下腔静脉组织中Atg5、LC3蛋白表达,免疫荧光共染明确平滑肌细胞中LC3表达。结果WT小鼠下腔静脉移植4周后出现管腔狭窄[(4.21±0.32)×10^4μm^2比(1.63±0.15)×10^4μum^2,P<0.05],Atg5[(0.51±0.17)×10^-3比(1.49±0.08)×10^-3]、LC3[(1.9±0.4)×10^-2比(3.8±0.9)×10^-2]mRNA表达均明显升高(均为P<0.05)。与WT小鼠相比,Atg5^+/-小鼠下腔静脉移植4周后Atg5[(0.39±0.05)比(0.16±0.08)]、LC3[(2.17±0.46)比(0.78±0.19)]蛋白表达均明显下降(均为P<0.05),平滑肌细胞中LC3蛋白表达显著下降(P<0.05),管腔狭窄明显减轻[(1.63±0.15)×10^4μm^2比(2.96±0.12)×10^4μm^2,P<0.05]。结论Atg5下调抑制小鼠下腔静脉移植术后静脉桥血管狭窄。     

冠状动脉旁路手术中动脉材料的选择与应用

目的 在冠状动脉旁路手术(CABG)中寻求动脉材料作旁路移植，减少因大隐静脉桥(SVG)阻塞对远期通畅率的影响。方法 34例冠心病患者以乳内动脉(IMA)和桡动脉(RA)作为血管桥行CABG，采用不接触血管技术制备动脉桥，应用药物防止动脉痉挛。结果 取乳内动脉35根，桡动脉20根，大隐静脉11根，平均移植血管1．94支，死亡1例，手术死亡率2．9％。结论 使用动脉材料行旁路移植术安全有效，预计能保持移植血管长期通畅。     

前降支旁路移植策略桥血管选择及通畅率研究

冠状动脉旁路移植术是治疗冠心病的有效手段。左前降支作为冠状动脉三大分支之一,其再血管化对于抢救患者生命、改善缺血症状非常重要,尤其是内乳动脉到左前降支的吻合至今仍是冠状动脉再血管化的“金标准”。对左前降支进行旁路移植术,可选择的桥血管材料包括游离或原位左右乳内动脉,游离或原位胃网膜右动脉,游离桡动脉、大隐静脉等。但是不同桥血管到左前降支的吻合策略和通畅率仍有待深入研究,本文总结了近30年的国内外文献资料,初步探讨不同桥血管选择策略及左前降支旁路移植的通畅率。     

右冠状动脉旁路移植策略及早期桥血管通畅率影响因素

目的:归纳右冠状动脉病变特点与旁路移植方式,探索影响右冠状动脉桥血管术中流量和术后早期通畅率的相关因素,为制定右冠状动脉旁路移植的策略提供依据。方法:回顾并筛选2017年8月至2019年6月在我院完成患多支血管复杂病变且行冠状动脉旁路移植术的冠心病患者,纳入其中靶血管包括右冠状动脉的患者241例,其中男性178例,女性63例,包含262支右冠状动脉区域桥血管。分析所有患者的临床基线资料、右冠状动脉造影病变特点、手术相关资料,统计不同旁路移植方式下右冠状动脉的特点,以及术中桥血管流量和术后早期桥血管通畅率的预测因素。结果:全组患者均干预右冠状动脉系统,241例患者以老年[(62.5±8.8)岁]、男性[178例(73.9%)]为主,其中合并高血压151例(62.7%)、NYHA心功能分级为Ⅰ/Ⅱ级55例(22.8%)。接受非体外循环旁路移植术153例(63.5%),平均靶血管数3.2个。右冠状动脉旁路移植部位选择的方式包括:单纯右冠状动脉主干旁路移植76例(31.5%),单纯后降支(PDA)旁路移植81例(33.6%),单纯左心室后支(PL)旁路移植15例(6.2%),PDA+PL旁路移植54例(22.4%),右冠状动脉主干+PDA旁路移植12例(5.0%),右冠状动脉主干+PL旁路移植3例(1.2%)。术后总体桥血管通畅率为96.2%。多重线性回归分析显示,靶血管吻合于右冠状动脉远端分支的桥血管流量预测值差于吻合于右冠状动脉主干(B=-11.126,P0.001),序贯吻合与非序贯吻合相比其桥血管流量显著提高(B=19.954,P0.001),而桡动脉桥是预测术后早期桥血管闭塞的独立危险因素(OR=21.973,95%CI:4.657～103.687,P0.001)。结论:移植于右冠状动脉主干和序贯吻合桥可能是提高桥血管流量的独立因素;而桡动脉桥是术后早期桥血管显影不佳的独立危险因素。     

序贯桥终末端与细小靶冠状动脉侧侧和端侧吻合的疗效对比

目的:评估不停跳冠状动脉旁路移植术中,分别采用侧侧吻合与端侧吻合方式缝合大隐静脉序贯桥终末端与细小靶冠状动脉的疗效。方法:回顾性分析2012年10月至2013年4月,行不停跳冠状动脉旁路移植术且终末靶冠状动脉细小的患者共89例。其中37例患者使用侧侧吻合术,即采用侧侧吻合方法缝合大隐静脉序贯桥终末端与靶冠状动脉;52例患者使用端侧吻合术,即将大隐静脉序贯桥终末端与靶冠状动脉进行端侧吻合。术中监测桥血管流量及搏动指数,术后6个月复查超声心动图、心电图等指标,以评估手术疗效。术后1年行双源CT冠状动脉造影检查,观察终末桥血管的通畅情况。结果:两组术中终末桥血管流量分别为[(17.32±6.18)vs.(14.15±5.09)mL/min,P0.05],搏动指数分别为[(2.50±1.08)vs.(3.47±0.74),P0.05]。两组患者在围术期内均无低心排出量综合征(低心排)、恶性心律失常及心肌梗死等不良事件发生。术后6个月复查超声心动图,提示两组患者心功能均较术前改善,但两组之间差异无统计学意义(P0.05)。术后随访1年时侧侧吻合组患者均无心绞痛发作,端侧吻合组有9例患者再发心绞痛。双源CT冠状动脉造影提示:侧侧吻合组中终末桥血管均保持通畅,而端侧吻合组中8例患者的终末桥血管再狭窄(P0.05)。随访截至2014年1月底,平均随访时间为(10.7±2.5)个月,患者随访率为100%,存活率为100%。结论:采用侧侧吻合术缝合大隐静脉序贯桥终末端与细小靶冠状动脉,可改善终末桥血管的通畅性。     

冠状动脉旁路移植术后静脉移植物内膜增生的发病机制

动脉桥管在冠状动脉旁路移植术中广泛使用且明显提高了远期效果,但静脉移植物仍然是使用最多的桥管.研究表明静脉移植物10年通畅率约为60%.静脉移植物再狭窄发病机制包括血流动力学变化导致血管壁受损,血栓形成和血管平滑肌迁移、增生,以及随后发生动脉粥样改变等.本文就静脉移植物再狭窄的发生机制作一综述.     

Local Delivery of Pravastatin Inhibits Intimal Formation in a Mouse Vein Graft Model

Background

Pravastatin can reduce atherosclerotic progression in patients after coronary artery bypass graft. However, it is unknown whether pravastatin has a direct effect on intimal hyperplasia of grafted vessels in vivo or what the underlying mechanisms may be. In this study, a murine vein graft model was applied to deal with these issues.

Methods

Vein grafting was performed between C57BL/6J mice. Immediately after operation, pravastatin (30 μM) or phosphate-buffered saline in 50 μL 20% pluronic F-127 gel was delivered to the adventitia of grafted vessels.

Results

Compared with the vehicle, pravastatin significantly reduced intimal hyperplasia 4 weeks after the surgical procedure. Immunohistochemical studies revealed that vascular smooth muscle cells (VSMCs) are a major component of the neointima. The percentage of cells positive for proliferating cell nuclear antigen and Mac-3-positive immunostaining intensity within the intima of vein grafts was significantly lower in the pravastatin-treated group than in the control group. We separated VSMCs from mouse inferior vena cava and collected peritoneal macrophage from mice injected intraperitoneally with 4% thioglycollate. Pravastatin significantly decreased VSMC proliferation and platelet-derived growth factor–induced VSMC migration and, in a dose-dependent manner, inhibited macrophage migration induced by monocyte chemotactic protein-1.

Conclusions

Local delivery of pravastatin at the time of vein-graft surgery directly suppresses subsequent neointimal formation of grafted vessels in a vein graft model of normocholesterolemic mice. These beneficial effects are associated with inhibitory actions on VSMC and macrophage functions.     

Noninvasive assessment of aorta-coronary saphenous vein bypass graft patency using thermocouple.

Noninvasive monitoring of patency of aorta-coronary bypass grafts can be achieved with reasonable accuracy using the thermocouple. This method is consisted of attaching the thermocouple to the surface of grafted vein during surgery and judging the patency by rapid injection of iced solution into peripheral vein. Patient grafted vein will show the thermal change after injecting iced solution. On the contrary, occluded graft will show no thermal change. As this thermal curve is a thermodilution curve by a single injection and is measured from the outside of the vessel, thermal change depends on the temperature and the quantity of the injected solution, cardiac output, body temperature, and loss of indicator temperature along the way to the thermocouple. When the grafted vein is patent, the same thermal curves are recorded regardless of the amount of the flow, and zero flow resulted in disappearance of curve. Initially, the method was evaluated in dogs and the appropriateness was verified. Subsequently, this method was applied to 16 vein grafts of 12 patients undergoing aorta-coronary bypass surgery. Ten or 15 ml of iced solution was injected through inferior vena cava or antecubital vein and the thermal change of the grafted vein was recorded for 1-4 weeks after the operation. Fourteen grafted veins were judged to be patent and 2 were occluded. The comparison of the results by this method with coronary angiography undergone at 4 weeks after the operation showed no false positive case but 1 false negative case. This extravascular observation of the thermodilution curve is a convenient method for judging whether vein graft is patent or not.     

冠状动脉旁路移植术再狭窄中PCNA蛋白表达的研究

目的　研究 PCNA基因片段对冠状动脉旁路移植术再狭窄的作用。方法　 2 5只健康纯种新西兰大耳白兔随机分五组 ,每组 5只。将颈外静脉移植于同侧颈总动脉 ,分别在术后 6 h,2 d,7d,14 d,2 8d取材。应用免疫组化和形态学分析观察不同时间 PCNA阳性细胞数的表达 ,采用计算机图象分析法测量静脉桥管腔内膜 ,中膜厚度及其比值。结果　实验过程中无实验动物死亡。吻合完成时各吻合口均通畅。在 7d时内膜和中膜厚度较 6 h明显增厚 ,有显著性差异 (P<0 .0 1)。而在 14 d、2 8d时内膜和中膜厚度较 7d没有明显变化 ,无显著性差异 (P>0 .0 5 )。移植后 6 h至 7d,在血管平滑肌细胞 (VSMC)中 ,PCNA蛋白逐渐增多 ,于 7d达高峰 (P<0 .0 1)。移植后 14 d PCNA蛋白在 VSMC中开始下降 ,与 7d相比差异有显著意义 (P<0 .0 1)。结论　 PCNA阳性细胞数在移植后 7d达高峰。与内膜迅速增殖的高峰期相吻合。提示 PCNA蛋白表达与内膜增殖有密切联系 ,可做为一个早期指标反应血管损伤后内膜的增殖     

Reduced neointima hyperplasia of vein bypass grafts in intercellular adhesion molecule-1-deficient mice

Recently, we established a new mouse model of vein graft arteriosclerosis through the grafting of vena cava to carotid arteries. In many respects, the morphological features of this murine vascular graft model resemble those of human venous bypass graft disease. With this model, we studied the role of intercellular adhesion molecule-1 (ICAM-1) in the development of vein graft arteriosclerosis in ICAM-1-deficient mice. Neointimal hyperplasia of vein grafts in ICAM-1 -/- mice was reduced 30% to 50% compared with that of wild-type control animals. Immmunofluorescent analysis revealed that increased ICAM-1 expression was observed on the endothelium and smooth muscle cells (SMCs) of the grafted veins in wild-type, but not ICAM-1 -/-, mice. MAC-1 (CD11b/18)-positive cells that adhered to the surface of vein grafts in ICAM-1 -/- mice were significantly less as identified with en face immunofluorescence, and these positive cells were more abundant in the intimal lesions of vein grafts in wild-type mice. Furthermore, aortic SMCs cultivated from wild-type mice exhibited high ICAM-1 expression in response to tumor necrosis factor-alpha. When tumor necrosis factor-alpha-stimulated SMCs were incubated with mouse spleen leukocytes, the number of cells that adhered to ICAM-1 -/- SMCs was significantly lower than the number that adhered to ICAM-1 +/+ SMCs, which was markedly blocked through pretreatment of leukocytes with the anti-MAC-1 antibody. Taken together, our findings demonstrate that ICAM-1 is critical in the development of venous bypass graft arteriosclerosis, which provides essential information for therapeutic intervention for vein graft disease in patients undergoing bypass surgery.     

Enhanced superoxide production in experimental venous bypass graft intimal hyperplasia: role of NAD(P)H oxidase

-Vein graft intimal hyperplasia, due to smooth muscle cell (SMC) proliferation, remains a limiting factor in long-term vein graft patency. Increased superoxide production regulates SMC mitogenesis and contributes to reduced NO bioactivity in systemic models of vascular disease. We compared superoxide production in experimental venous bypass grafts with ungrafted veins and determined its enzymatic sources and cellular localization. Vascular superoxide production was measured in vein grafts and control jugular veins obtained from normocholesterolemic rabbits undergoing jugular vein-carotid artery interposition bypass grafting. Surgical isolation of the contralateral jugular vein, without bypass grafting, provided an additional control for the effects of surgical manipulation. Superoxide production was increased 3-fold in vein grafts compared with control veins. Systematic stimulation and inhibition of specific oxidases revealed that the major source of increased vein graft superoxide production was a membrane-associated NAD(P)H-dependent oxidase. Western blotting of vascular homogenates demonstrated corresponding increases in NAD(P)H oxidase p22phox (membrane-associated) and p67phox (cytosolic) subunits in vein grafts compared with jugular veins. There was marked intimal hyperplasia in vein grafts, and immunohistochemical staining of vessel cryosections revealed increased p22phox-expressing cells in vein grafts that were predominantly intimal SMCs. Superoxide generation is increased in experimental vein grafts compared with ungrafted veins. The principal source of increased superoxide generation in vein grafts is an NAD(P)H oxidase, expressed by intimal SMCs. These findings suggest a role for NAD(P)H oxidase-mediated superoxide production in the proliferative response to vascular injury in vein grafts.     

Coronary vein graft disease: Pathogenesis and prevention

Not long after coronary artery bypass grafting surgery was described, several reports presented follow-up angiographic data on large cohorts of patients, demonstrating that approximately one-half of saphenous vein grafts fail within 10 to 15 years of surgery and that graft failure is associated with worse clinical outcomes. Three processes are responsible for vein graft failure. Thrombosis, intimal hyperplasia and accelerated atherosclerosis contribute to graft failure in the acute, subacute and late postoperative periods, respectively. Studies have shown that perioperative antiplatelet therapy can reduce early thrombosis and graft failure. As in native coronaries, intensive lipid lowering can attenuate the process of atherosclerosis in vein grafts. Intimal hyperplasia in the vein graft is thought to be an adaptation of the vein to higher pressures in the arterial circulation. This process is further promoted by the loss of inhibition from the endothelial layer, which is injured during surgery. A new ‘no-touch’ technique for harvesting grafts may be effective in preventing disruption to the endothelial layer, and subsequent intimal hyperplasia and graft loss. Off-pump surgery and endoscopic vein harvesting, which are known to reduce surgical morbidity, have been shown to be no worse than on-pump surgery and open vein harvesting, respectively, in terms of vein graft patency. Various gene therapies can prevent intimal hyperplasia in animal models, but human data obtained so far have been disappointing. Placing an external stent around a vein graft may reduce tangential wall stress and subsequent intimal hyperplasia.