Perivenous application of fibrin glue reduces early injury to the human saphenous vein graft wall in an ex vivo model.

OBJECTIVES: From animal and clinical studies it is known that prevention of 'over-distention' of vein grafts by using extravascular support ameliorates the arterialization process in vein grafts with subsequent more favorable patency. The most ideal support is a biodegradable, porous, elastic graft (Biomaterials, 15 (1994) 83). However, a specific graft meeting these criteria is not available yet. Fibrin glue on the other hand, although used for other purposes in cardiac surgery, theoretically meets the criteria for ideal extravascular support. In this ex vivo study, we evaluated the possible beneficial effect of perivenous application of fibrin glue. METHODS: Segments of human vein graft obtained during CABG procedures in 14 consecutive patients were placed in a side loop of the extracorporeal perfusion circuit. In this way the study vein grafts did meet identical circumstances as the vein grafts implanted. Perfusion in the loop was started with a flow just enough to counteract the collapse of the vein, usually about 8 mm Hg, and alternately around the segments fibrin glue was applied or no perivenous support was administered as control. After 1 min of soldification, perfusion was started with a pressure of about 60 mm Hg (non-pulsatile flow). Perfusion was maintained for 60 min, after which the grafts were collected for light microscopic and electron microscopic assessment. RESULTS: Light microscopy and electron microscopy showed remarkable attenuation of endothelial cell loss and less injury of smooth muscle cells of the circular muscle layer of the media in the fibrin glue supported vein grafts compared to the non-supported group. CONCLUSION: Fibrin glue is able to accomplish adequate external vein graft support, preventing overdistention, in an ex vivo model. This provides a basis for clinical application. Further investigation is necessary to evaluate long-term effects.     

Angiographic studies of atherosclerotic changes in coronary vein grafts after operation]

A total of 230 vein grafts were studied angiographically in 116 unselected survivors of 260 coronary bypass operations performed from May 1977 through October 1989 in order to investigate atherosclerotic changes in coronary vein grafts after operation. These patients were divided into three groups according to the interval from operation to angiography. In group A (30 patients) the interval was less than one year (mean interval 8.2 months), in group B (73 patients) from one to five years (mean interval 19.2 months) and in group C (13 patients) more than 5 years (mean interval 96.6 months). Fifty-five vein grafts were in group A, 153 vein grafts in group B and 22 vein grafts in group C. The graft patency rate of each group was 83.6%, 89.5% and 90.9% respectively (N.S.). To classify angiographic appearances we believe to be caused by atherosclerosis, we devised a grading system. Category I indicated that the graft outline was completely smooth without any irregularity; Category II indicated that less than 50% of the estimated surface area of the graft intima was irregular; Category III indicated that more than 50% of the intima was involved. Significant stenosis indicated narrowing reducing the lumen to less than 50% of the graft. Of the 203 patent grafts 181 grafts (89%) were in Category I, 22 grafts (11%) in Category II, but no graft in Category III. In group A of the 46 patent grafts 45 grafts (98%) were classified as Category I and 1 graft (2%) was classified as Category II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic changes in blood flow alter endothelium-dependent responses in autogenous vein grafts in dogs

Purpose: Experiments were designed to determine the effects of blood flow on endothelium-dependent relaxations in canine vein grafts.Methods: Blood flow through reversed femoral vein grafts was either increased by a distal arteriovenous fistula (increased flow), unmanipulated (normal flow), or reduced by a proximal adjustable clamp (reduced flow). Six weeks after implantation, blood flow through the graft was measured. Rings cut from grafts were suspended for the measurement of isometric force in organ chambers to determine endothelial function.Results: Blood flow was significantly greater in grafts with a distal fistula compared to grafts with normal or decreased flow. Endothelium-dependent relaxations to acetylcholine were absent in all grafts. Endothelium-dependent relaxations to adenosine diphosphate, thrombin, and the calcium ionophore A23187 were less in grafts with reduced flow compared with grafts with increased flow. Relaxations to these agents in grafts with increased flow were reduced by an analog of L-arginine. Neointimal hyperplasia was increased in grafts with reduced flow.Conclusions: These data demonstrate that chronic diminution of blood flow decreases receptor-mediated release of endothelium-derived relaxing factors and increases neointimal hyperplasia in canine vein grafts. The production of endothelium-derived relaxing factors, one of which is nitric oxide, may influence the development of myointimal hyperplasia in vein grafts. (J VASC SURG 1994;20:765-73.)     

Mechanical and histologic changes in canine vein grafts

Mechanical and histological studies were performed on dog femoral veins after their implantation as grafts to bypass the ligated femoral arteries. The vein grafts dilated rapidly after implantation with 90% of maximum dilation occurring at 4 weeks. Both the native veins and the vein grafts were highly compliant up to 35-50 mm Hg, but were virtually nondistensible at higher pressures. When implanted with end-to-side anastomoses (end of vein to side of artery), the compliance of the anastomotic region resembled that of the artery rather than that of the vein. This was due to the distensibility of the artery at arterial pressure, as compared with the almost rigid vein. Histologic examination showed that intimal hyperplasia was greater after end-to-side anastomosis than after end-to-end anastomosis (P less than 0.05) and that this increased hyperplasia was reduced by treatment with aspirin and dipyridamole (P less than 0.05). By contrast, medial thickening was increased in all grafts compared with native veins (P less than 0.05), but was not different in end-to-end, end-to-side, and aspirin/dipyridamole-treated end-to-side grafts. These data suggest that intimal hyperplasia and medial thickening are separate responses to different stimuli.     

Compliance changes in in-situ femoropopliteal bypass vein grafts

Changes in wall structure, including neo-intimal proliferation and medial fibrosis, have been implicated as a cause of late occlusion in reversed femoropopliteal vein grafts. These changes can be measured indirectly as a fall in compliance. It has been suggested that long-term patency might be improved by the in situ technique because the nutrient vasa vasorum are left intact and therefore wall structure preserved. We have measured the compliance of 62 in situ vein grafts, with times after operation ranging from 2 days to 6 years, and also compared the compliance changes, in the first 3 months after operation, of 15 undisturbed in situ vein grafts with 15 fully mobilized in situ vein grafts. Compliance was derived non-invasively from the pulse wave velocity using Doppler ultrasound. There was a significant fall in compliance after operation (P less than 0.001) and no difference could be found between the undisturbed and mobilized in situ vein grafts (P greater than 0.1). Histological examination of 6 grafts suggested that the fall in compliance was due to neo-intimal proliferation which still occurred although medial fibrosis was reduced. Any potential improvement in long-term patency rates using the in situ technique must be due to other factors.     

Degenerative changes of vein grafts in preparation media: Preliminary studies by electron microscopy and fibrinolytic autography

Degenerative changes of saphenous vein grafts in four preparation media (heparinized whole blood at room temperature and 4°C, and heparinized normal saline at same temperatures) were examined by scanning and transmission electron microscopy and fibrinolytic autography. Following 60–90 min. storage in heparinized normal saline at room temperature, marked morphological changes were present in the media, accompanied by swellingof the endothelial cells, however the tunica media and adventitia were well preserved even after 120 minutes in all of the four preparation media. The decrease in fibrinolytic activity was comparable to the observed morphological changes. In heparinized whole blood at 4°C, degenerative changes were slow and mostly of a slight nature.     

Early adaptation of human lower extremity vein grafts: wall stiffness changes accompany geometric remodeling

OBJECTIVE: To quantitatively describe the temporal changes in elastic properties and wall dimensions in lower-extremity vein grafts after implantation. DESIGN OF STUDY: This is a prospective study of patients (N = 38) undergoing lower extremity bypass grafts (N = 41) with autologous veins. Pulse wave velocity (PWV), luminal diameter, and wall thickness measurements were obtained by duplex ultrasound scan intraoperatively and at 1, 3, and 6 months postoperatively for assessment of graft dimensions and wall stiffness. RESULTS: Lower extremity vein grafts showed an increase in PWV (from 16 +/- 1 to 21 +/- 3 cm/s; mean +/- SEM; P =.08), reflecting an increase in wall stiffness (from 1.2 +/- 0.2 to 2.5 +/- 0.7 x 10(6) dynes/cm; P =.02) and wall thickness (from 0.47 +/- 0.03 to 0.61 +/- 0.004 mm; P =.04) over the first 6 months after implantation. Changes in lumen diameter were positively correlated with changes in external graft diameter (P <.01) and negatively correlated with initial lumen diameter (P <.01) but not with changes in the wall thickness. CONCLUSIONS: These results suggest complex remodeling of vein grafts during the first several months after implantation, with increased wall thickness occurring independent of variable changes in lumen diameter. Simultaneously, a marked increase in wall stiffness over this interval suggests a likely role for collagen deposition.     

Heparin reduces the intimal hyperplasia seen in microvascular vein grafts.

The influence of heparin on microvascular vein graft intimal hyperplasia was studied in a rat model. The iliolumbar vein was grafted into the iliac artery in 80 rats. Heparin was delivered via a subcutaneous miniosmotic pump, starting either 2 days before grafting (early heparin group, n = 20) or immediately after grafting (heparin group, n = 30). Saline-containing pumps were placed in the control group (n = 30). Heparin activity was measured at 24 h, and again 3 weeks later when the animals were sacrificed. The grafts were harvested and prepared for histological examination. The intimal thickness was measured at the anastomoses and in the mid-graft region using an eye-piece graticule set at right angles to the graft internal elastic lamina. Heparin significantly reduced the intimal thickness at the anastomoses, from a median of 38 microns (range: 10-100 microns) in the control group to a median of 20 microns (range: 10-150 microns) in the heparin group. A similar reduction was seen in the mid-graft region. Although intimal thickening was reduced in the early heparin group, this reduction failed to reach statistical significance. The possible clinical application is discussed.     

Chronic ACE inhibition reduces intimal hyperplasia in experimental vein grafts.

Intimal hyperplasia is an important factor in the pathophysiology of vein graft failure. Local renin-angiotensin systems recently have been shown to modulate the development of intimal hyperplasia in arteries after intimal injury. The effect of chronic angiotensin-converting enzyme (ACE) inhibition on the development of intimal hyperplasia in experimental vein grafts was examined in this study. Ten New Zealand White rabbits received 10 mg/kg of captopril daily in their drinking water. One week later the right carotid artery was divided and bypassed with the reversed right external jugular vein in these rabbits and in 10 matched controls. Captopril was continued for 28 days after operation, when all the grafts were harvested. Five grafts from each group were perfusion fixed, and the intimal thickness in the proximal, middle, and distal segments was determined. Rings from the remaining grafts (n = 20 in each group) were studied in vitro under isometric tension, and their responses to norepinephrine (NE), histamine (HIST), serotonin (5-HT), angiotensin I (AI), and angiotensin II (AII) was measured. The intimal thickness of the proximal, middle, and distal segments of the captopril-treated grafts were significantly less than controls, being reduced in all segments by approximately 40% (p less than 0.0001). With regard to vasoreactivity, the captopril-treated grafts were hypersensitive to 5-HT (control ED50 5.5 +/- 0.5 X 10(-7) mol/L vs. captopril-treated 1.1 +/- 0.2 X 10(-6) mol/L; p less than 0.005) although the maximal response was significantly reduced (control 1.6 +/- 0.3 g vs. captopril-treated 0.8 +/- 0.1 g; p less than 0.05). There were no differences in sensitivity between control and captopril-treated rings with respect to NE, HIST, AI, or AII. Four of the ten captopril-treated segments, however, failed to respond to AI, and the maximal active tension of the responders was significantly reduced (control 0.47 +/- 0.06 g vs. 0.20 +/- 0.05 g; p less than 0.02). These results suggest that ACE is involved in the modulation of vein graft intimal hyperplasia, and that ACE inhibitors may have therapeutic applications in patients undergoing vein bypass procedures.     

可降解壳聚糖血管外周支持与静脉移植物早期结构的变化

目的　探讨可降解壳聚糖血管外周支持 (CES)对静脉移植物 (VG)早期结构变化的影响 ,为临床提高VG通畅率提供新的治疗方法。　方法　将兔右颈内静脉端 端吻合于同侧颈总动脉建立静脉移植模型 ,以有无CES干预分为支架组与无支架组 (每组 2 4只兔 )。术后 1、2、4周分别切除移植静脉 ,计算机图像分析系统测量和计算内膜、中膜厚度和面积 ,免疫组织化学法检测增殖细胞核抗原 (PCNA)指数观察平滑肌细胞增殖程度。　结果　CES在术后 2周开始降解。支架组VG ,术后 1～ 2周内膜、中膜的厚度和面积、PCNA指数在术后 1周轻度增加 ,1～ 2周维持稳定 ,术后 2周分别为(2 6 3± 3 7) μm、(2 6 0± 1 9) μm、(0 5 6± 0 0 8)mm2 、(0 34± 0 0 5 )mm2 与 (11 5± 2 1) % ,明显低于无支架组的 (5 6 4± 9 4 ) μm、(47 6± 4 9) μm、(1 17± 0 0 8)mm2 、(1 2 0± 0 4 3)mm2 与 (36 6± 2 9) % (P <0 0 1) ;术后 4周虽然又增加 ,分别为 (31 7± 1 6 ) μm、(31 7± 1 6 ) μm、(0 72± 0 12 )mm2 、(0 4 2± 0 0 6 )mm2 与 (13 4± 1 2 ) % ,但仍低于无支架组的 (76 8± 8 0 ) μm、(5 7 4± 9 5 ) μm、(1 2 7± 0 17)mm2 、(1 2 7± 0 0 9)mm2 与 (16 8± 2 2 ) % (P <0 0 5 )。结论　CES     

Pathological changes in surgically removed aortocoronary vein grafts.

Pathological changes in aortocoronary vein grafts were investigated in 17 patients who had a second revascularization procedure 1 to 53 1/2 months after their initial operation. Subendothelial proliferation was present in all grafts and had resulted in total occlusion of 7. With increasing duration of implantation the proliferative lesions tended to show hyalinization and to affect the media. Advanced atherosclerosis had developed in 2 grafts.