Performance of a polyurethane vascular prosthesis carrying a dipyridamole (Persantin) coating on its lumenal surface

A porous polyurethane vascular prosthesis with an internal diameter of 5 mm was studied. The graft carries a coating of immobilized dipyridamole (Persantin(R)) on the surface of its lumen. Dipyridamole is a potent nontoxic inhibitor of platelet activation/aggregation, and also a strong inhibitor of vascular smooth muscle cell proliferation. The polyurethane material is also known as Chronoflex(R), and already finds use as a vascular access graft. The coated vascular graft was studied in vitro (hemocompatibility, interaction with blood platelets and cultured endothelial cells), as well as in two established in vivo models. In the first in vivo study, coated grafts were implanted in goats, as a bypass of the carotid artery (four animals, eight grafts, length of the graft was approximately 12 cm). Four uncoated grafts were used as controls in otherwise identical experiments. In the second in vivo experiment, eight sheep were used. Each animal received one coated and one uncoated prosthesis as an interposition graft in the carotid artery (length of the graft was 4 cm). The in vitro experiments revealed that the dipyridamole coating has three beneficial effects: reduced thrombogenicity, reduced adherence of blood platelets, and accommodation of a confluent monolayer of endothelial cells. The goat experiments showed patency of the coated grafts in three of the eight cases. The sheep experiments were not useful for the evaluation of the dipyridamole coating because deterioration of the polyurethane material was observed. The in vivo results indicate that the dipyridamole coating may positively influence the patency rate, probably because the coating promotes the growth of an endothelial cell lining. The sheep data show, however, that the limited stability of the Chronoflex(R) material precludes its issue for the construction of permanent small-bore vascular grafts.     

Thallium scintigraphy in prediction of occlusion of bypass grafts in asymptomatic and symptomatic patients

To evaluate thallium scintigraphy in predicting coronary artery bypass graft patency, exercise thallium scintigraphy and selective graft and native vessel angiograms were performed in 22 asymptomatic and 29 symptomatic consecutive patients three months after coronary artery bypass grafting (CABG). Twelve out of 22 asymptomatic patients (55%) had reversible thallium defects on postoperative images; in 10 patients the postoperative scans were normal. The graft patency was significantly lower in asymptomatic patients with abnormal thallium perfusion compared to those with normal perfusion after CABG (68% vs. 91%, p less than 0.05). The rate of graft patency in symptomatic patients was 66/87 (76%). Thallium scintigraphy was 77% sensitive and 78% specific in detecting one or more stenosed or occluded bypass grafts in patients without angina (accuracy 77%). When data from exercise electrocardiography were combined with scintigraphy, all but one patient with incomplete revascularization could be detected (positive predictive accuracy 92%). In symptomatic patients, thallium scintigraphy accurately predicted the presence or absence of graft occlusion in 24/29 (83%) cases. Thus, abnormal myocardial perfusion due to stenosis or occlusion of bypass grafts is common in both asymptomatic and symptomatic patients after CABG. Thallium scintigraphy together with exercise electrocardiography appear to be useful non-invasive methods in detecting painless myocardial ischemia and in predicting bypass graft occlusion after CABG.     

Histologic findings after in vivo placement of small intestine submucosal vascular grafts and saphenous vein grafts in the carotid artery in dogs.

A small caliber vascular graft from porcine small intestine submucosa (SIS) was implanted in a canine carotid artery (n = 24) and compared with an autogenous saphenous vein graft that was implanted in the contralateral carotid artery. In this study, four grafts were evaluated at the following times after surgery: 2, 7, 14, 28, 90, and 180 days. One SIS graft thrombosed at 2 days, two SIS and two saphenous vein grafts were thrombosed at 90 days, and one SIS and one saphenous vein graft were thrombosed at 180 days. At 2 days after implant, the luminal surface of the SIS graft was covered by a thin (30 mu) fibrin meshwork. By 14 days after surgery, endothelial cells on the fibrin meshwork were staining for FVIII-related antigen. Smooth muscle cells were observed in the new intima (fibrin meshwork) by 28 days. At 90 days, both types of graft had arterialized with an intima covered by endothelium, a smooth muscle media, and marked adventitial fibrosis. Similar histology was observed at 180 days. These results indicate that this SIS graft was similar to saphenous vein graft in the dog.     

Induction of neointima formation by platelet derived angiogenesis fraction in a small diameter, wide pore, PTFE graft.

Enhancement of endothelialization and patency of a small diameter (2 mm), wide pore, PTFE graft was attempted by coating the luminal surface with a platelet derived angiogenesis fraction (PDAF) and implanting it in a rat model. PDAF was delivered to the grafts by combining it with a carrier polymer. PDAF-treated grafts were initially implanted in the retroperitoneum for 21 days followed by removal of one for histology and in situ end to side bypass to the infrarenal aorta for the other. Vascularized grafts were examined at 14 days for patency and 100 days for patency and histology. Significant differences were noted in transmural ingrowth of capillaries and tissue at 21 days post implantation in PDAF-treated versus untreated grafts. Similarly, near significance was noted in capillary ingrowth and significance was noted in tissue ingrowth at 100 days in PDAF-treated grafts. Despite favorable trends particularly early in the time course, no significant differences in graft patency, endothelialization, or hydroxyproline content was demonstrated between PDAF-treated and untreated grafts. Results of this preliminary study are encouraging for further study of PDAF-treated PTFE grafts and the potential that rapid vascularized neointima formation results improved in graft patency rates.     

Both skeletonized and pedicled internal thoracic arteries supply adequate graft flow after coronary artery bypass grafting even during intense sympathoexcitation

The internal thoracic artery (ITA) is harvested by either the pedicled or the skeletonized technique in coronary artery bypass grafting (CABG), with no clear advantage of one technique over the other. We compared graft flow between the pedicled and skeletonized ITA grafts while varying myocardial oxygen demand. CABG was performed to the left anterior descending artery in five anesthetized dogs using a pedicled ITA graft and the graft was subsequently skeletonized. Graft flow was measured during stepwise electrical stimulation of the stellate ganglion. The baseline graft flow before sympathetic stimulation was higher in skeletonized (27.8 ± 1.9 ml/min) than that in pedicled ITA grafts (22.6 ± 2.7 ml/min) (P < 0.05). In both ITA grafts, however, graft flow increased to a similar level during sympathetic stimulation that doubled the double product, correlating with the double product. Based on these results, we conclude that metabolic demand can override the potential difference in sympathetic vasoconstriction in both pedicled and skeletonized ITA grafts.     

Assessment of coronary artery bypass graft patency by multislice computed tomography

The recently developed multislice computed tomography (MSCT) is capable of rapid imaging of cardiac structures, including coronary arteries, during a single breath-hold. We evaluated coronary artery bypass graft (CABG) patency by comparing MSCT results to those of contrast angiography. MSCT and contrast angiography were performed in 39 patients (10 women, 29 men and mean age 60.0 +/- 7.8 years) with a total of 115 bypass grafts including 36 left internal mammary arteries, 4 right internal mammary arteries, 19 radial arteries, 2 gastroepiploic arteries and 54 vein grafts. Patients were investigated for an average of 14 +/- 27 months (range 1 - 108 months) after CABG surgery. Contrast angiography showed a patency rate of 87.0% (100/115). Ninety-nine of these 100 patent grafts by contrast angiography and 14 of the remaining 15 occluded grafts were correctly classified by MSCT (93.3% sensitivity and 99.0% specificity for bypass graft occlusion). The positive and negative predictive values for bypass graft occlusion were 93.3% and 99%, respectively, with an overall diagnostic accuracy of 98.3% (97.2% for left internal mammary artery, 100% for radial artery, 98.1% for vein graft and 100% for other grafts). In conclusion, MSCT is a useful and accurate diagnostic tool for the evaluation of bypass graft patency.     

Estimation of wall shear stress in bypass grafts with computational fluid dynamics method

Coronary artery bypass graft (CABG) operation for coronary artery disease with different types of grafts has a large clinical application world wide. Immediately after this operation patients are usually relieved of their chest pain and have improved cardiac function. However, after a while, these bypass grafts may fail due to for example, neointimal hyperplasia or thrombosis. One of the causes for this bypass graft failure is assumed to be the blood flow with low wall shear stress. The aim of this research is to estimate the wall shear stress in a graft and thus to locate areas were wall shear stress is low. This was done with the help of a blood flow computer model. Post-operative biplane angiograms of the graft were recorded, and from these the three-dimensional geometry of the graft was reconstructed and imported into the computational fluid dynamics (CFD) program FLUENT. The stationary diastolic flow through the grafts was calculated, and the wall shear stress distribution was estimated. This procedure was carried out for one native vessel and two different types of bypass grafts. One bypass graft was a saphenous vein and the other one was a varicose saphenous vein encased in a fine, flexible metal mesh. The mesh was attached to give the graft a defined diameter. The computational results show that each graft has distinct areas of low wall shear stress. The graft with the metal mesh has an area of low wall shear stress (< 1 Pa, stationary flow), which is four times smaller than the respective areas in the other graft and in the native vessel. This is thought to be caused by the smaller and more uniform diameter of the metal mesh-reinforced graft.     

Arterial replacement with compliant hierarchic hybrid vascular graft: biomechanical adaptation and failure

Two types of hybrid vascular grafts were hierarchically structured with an autologous smooth muscle cell (SMC)-inoculated collagen gel layer and an endothelial cell (EC) monolayer, and wrapped with different elasomeric scaffolds. Type A graft was wrapped with poly(urethane)-nylon mesh, and type B graft was wrapped with an excimer laser-directed microporous segmented polyurethane (SPU) film as the scaffold. Type A graft was more compliant than canine carotid arteries, whereas compliance of type B graft was close to that of native arteries. After implantation into canine carotid arteries for 1 month, all type A grafts were dilated due to loosening of the mesh, resulting in loss of prelined ECs and thrombus formation. In contrast, type B grafts developed a well-organized neoarterial wall composed of a confluent EC monolayer and SMC-resided medial tissue, resulting in only slightly appreciable thrombus and minimal tissue ingrowth 6 months after implantation. Compliance of type B graft was reduced at 6 month's implantation, which is mostly due to encapsulated connective tissue formed around the graft.     

组织型纤溶酶原激活剂在移植血管桥再狭窄动物血管的差异表达

目的研究组织型纤溶酶原激活剂（t—PA／PLAT）在移植血管桥再狭窄动物血管的差异表达。方法通过兔双侧颈动脉进行动脉桥和静脉桥的移植,形成双侧移植血管桥再狭窄动物模型。应用免疫组化检测t-PA在动物模型动脉桥、静脉桥的表达并进行比较。结果血管桥移植前,t-PA在实验动物颈动脉和颈静脉的表达差异无统计学意义（P〉0．05）;血管桥移植后,t-PA在动脉桥的表达明显高于静脉桥（P〈0．05）,于16周时达到高峰[（32．34±4．74）％比（16．74±3．14）％],以后随时间延长而出现表达减少（P〈0．05）。结论t-PA在术后早期对血管桥具有保护作用,其表达的高低与术后血管桥再狭窄关系密切。     

A new vascular polyester prosthesis impregnated with cross-linked dextran

It is essential that a synthetic vascular graft is preclotting prior to implantation in order to prevent blood leaking through the graft wall. We have impregnated a knitted polyester prosthesis with cross-linked dextran. The aim of this study was to develop a process for obtaining an impervious prosthesis and to compare the characteristics of this dextran-impregnated graft with those of a commercially available collagen-impregnated graft. This new vascular prosthesis was coated with dextran; sodium trimetaphosphate was utilized as the cross-linking agent. In an attempt to determine the optimal conditions for impregnation, the dynamic viscosity of the dextran solution was measured during the cross-linking reaction. The results suggest that the dynamic viscosity is correlated with the concentrations of dextran, sodium hydroxide, and sodium trimetaphosphate. The effect of temperature on the dynamic viscosity was also investigated. The water permeability, the coating weight, and the structure of the dextran-impregnated graft were compared with those of a collagen-impregnated prosthesis. The water permeability of the vascular grafts was reduced by dextran impregnation, from 1010 ml/min per cm2 for the control to 0.04 ml/min per cm2 under standard testing conditions. The dextran coating is capable of rendering the graft impervious to water. The coating weight of the graft treated with dextran was approximately the same as the weight of the collagen-impregnated graft. Finally, the morphology of the prosthetic wall was analyzed using scanning electron microscopy. The promotion of endothelial cell recovery was only observed for the polyester grafts treated with dextran or collagen.     

桡动脉在全动脉化冠脉搭桥术中的临床应用

目的探讨桡动脉在全动脉化冠脉搭桥术中的临床应用效果。方法22例患者采用乳内动脉和桡动脉行全动脉化冠脉搭桥手术,"不接触血管技术"游离桡动脉,与冠状动脉对角支、钝缘支、前降支、右冠状动脉等单独或序贯吻合,共搭桥31支。术后应用钙通道阻滞剂防止桡动脉痉挛。结果22例手术均顺利完成,痊愈出院,无围术期心肌梗塞,术后心肌缺血改善,无手部缺血并发症。随访2月～3年,无心绞痛复发,手部功能正常。结论桡动脉作为血管桥材料在全动脉化冠脉搭桥术中应用效果良好。     

Evaluation of alginate dialdehyde cross-linked gelatin hydrogel as a biodegradable sealant for polyester vascular graft

Vascular grafts are devices intended to replace compromised arteries in the body and grafts made of polyethylene terephthalate (PET) fabric have been used mainly for synthetic grafting procedures involving medium to large diameter vascular grafts. Though porosity of the graft permits tissue in-growth, it would lead to bleeding through the graft walls immediately after implantation. So it is essential to seal the pores either by preclotting with patient's own blood or by other sealing materials prior to implantation in order to prevent blood leakage through the graft wall. Biodegradable hydrogel materials are ideal candidates for this purpose. Apart from sealing the pores, they offer biocompatible and low-thrombogenic surfaces when coated on vascular graft. In the present study, a biodegradable hydrogel, derived from oxidized alginate and gelatin, has been deposited on PET grafts by dip coating and were characterized for its efficacy on sealing the pores of the graft. Water permeability in the static and pulsatile conditions, burst strength, in vitro cell culture cytotoxicity, hemocompatibility, and endothelial cell adhesion and proliferation of the coated grafts were investigated. Results showed that the alginate dialdehyde cross-linked gelatin hydrogel was nontoxic, hemocompatible, and was efficient in sealing the pores of the graft. Blood perfusion study showed that when hydrogel-coated grafts were exposed to blood for 30 min, they showed little affinity toward platelets or leukocytes. Hemolytic potential of PET was significantly reduced when it was coated with hydrogel. Improved adhesion and proliferation of endothelial cells were observed when PET grafts were coated with hydrogel. Results also showed that coating with hydrogel did not affect the burst strength of the PET graft.     

A new vascular polyester prosthesis impregnated with cross-linked dextran

It is essential that a synthetic vascular graft is preclotting prior to implantation in order to prevent blood leaking through the graft wall. We have impregnated a knitted polyester prosthesis with cross-linked dextran. The aim of this study was to develop a process for obtaining an impervious prosthesis and to compare the characteristics of this dextran-impregnated graft with those of a commercially available collagen-impregnated graft. This new vascular prosthesis was coated with dextran; sodium trimetaphosphate was utilized as the cross-linking agent. In an attempt to determine the optimal conditions for impregnation, the dynamic viscosity of the dextran solution was measured during the cross-linking reaction. The results suggest that the dynamic viscosity is correlated with the concentrations of dextran, sodium hydroxide, and sodium trimetaphosphate. The effect of temperature on the dynamic viscosity was also investigated. The water permeability, the coating weight, and the structure of the dextran-impregnated graft were compared with those of a collagen-impregnated prosthesis. The water permeability of the vascular grafts was reduced by dextran impregnation, from 1010 ml/min per cm² for the control to 0.04 ml/min per cm² under standard testing conditions. The dextran coating is capable of rendering the graft impervious to water. The coating weight of the graft treated with dextran was approximately the same as the weight of the collagen-impregnated graft. Finally, the morphology of the prosthetic wall was analyzed using scanning electron microscopy. The promotion of endothelial cell recovery was only observed for the polyester grafts treated with dextran or collagen.     

Evaluation of the thrombogenecity of microvascular prosthesis by in vivo microscopy.

Expanded polytetrafluoroethylene(ePTFE) grafts 4mm long and 1mm in diameter were implanted into the iliac artery of 100-150g male rats using standard microvascular technique. Prior to clamp removal, the cremaster muscle was isolated as an island flap based on the iliac artery and observed using intravital fluorescence microscopy. Fields which contained a bifurcation of a first order arteriole(80-100 microns diameter) into second order arteriole(50-80 microns) were chosen for observation. Platelets were labeled in vivo with acridine red to visualize and quantify the aggregates. Images of microemboli were counted manually and the area was measured by computerized planimetry. Six control grafts were implanted with no further processing, six were irrigated with heparin, and six were coated with tridodecylmethylammonium chloride(TDMAC) and heparin. Most thrombi appeared within the first five minutes after implantation in all groups. The total number of emboli observed in the control group was 91 pr animal, in the heparin irrigation group it was 84, and in the TDMAC-heparin group it was 22. The total thrombus area observed per animal was 137,660 +/- 29,467 microns 2 in the control group, 79,040 +/- 10,893 microns 2 in the heparin irrigation group, and 17,498 +/- 6,059 microns 2 in the TDMAC-heparin group (p < .01 vs control or heparin irrigation group). With this results we could find that heparin irrigation and TDMAC-heparin coating appear to reduce the number, size, and total amount of microemboli generated by ePTFE graft implantation and apparent thromboresistant property of TDMAC-heparin coating may have widespread application in many clinical and research areas and this experimental model can be used for evaluation of other graft matrials.     

动脉血流旋动原理在人造血管研制和血管移植术中的应用

目的 将血液流动的旋动流原理用于心血管介入治疗,以期解决小口径人造血管的急性血栓堵塞问题和搭桥手术后下游处血管内膜增生引起的血管再狭窄问题。方法 使用计算流体力学（CFD）分别研究具有旋动流特性的新型小口径、S型搭桥和偏心搭桥模型中的流场以及壁面剪切力的分布。同时研究在旋动流下血小板的黏附情况和不同角度的S型搭桥下的血管内膜增生。结果 旋动流能明显提高壁面剪切力,抑制血小板的黏附以及血管内膜增生。结论 在心血管介入治疗和器械设计中引入旋动流确实可明显改善这些器械中的血流流场,达到抑制小口径人造血管的急性血栓形成和搭桥手术后血管内膜增生的目的。     

In vivo protein adsorption on polymers: visualization of adsorbed proteins on vascular implants in dogs.

The absorption of plasma proteins is an important event at the blood-material interface, and strongly affects subsequent cellular interaction and thrombus formation. Although considerable efforts have been expended to elucidate the mechanism of protein adsorption and the role of absorbed protein layer at the blood-material interface, there has been little knowledge of how the initial adsorbed proteins are maintained or changed in a time-variant process in in vivo long-term implantation. In this study, we described detailed analyses concerning the characterization of adsorbed proteins on HEMA--styrene block copolymer surfaces (HEMA-st) and poly(ethylene oxide) (PEO) grafted Biomer (B-PEO4K) for in vivo long-term canine vascular graft implants as well as in vitro short-term experiments. Biomer vascular grafts (6 mm I.D., 7 cm in length) were fabricated by a dip coating and the luminal surface was modified with PEO grafting, HEMA-st coating, or Biomer coating (control). These surface modified grafts were recirculated for different time intervals (5, 15, 30, 60 and 120 min) using citrated canine whole blood. The grafts were then implanted in the abdominal aortas of dogs and evaluated for graft patency and protein adsorption. The adsorbed proteins (albumin, IgG and fibrinogen) were quantified using an in situ radioimmunoassay. Surface protein layer thickness was measured by transmission electron microscopy (TEM). Visualization of absorbed plasma proteins (albumin, IgG and fibrinogen) was performed with TEM using an immunoperoxidase double antibody technique. In in vitro recirculation systems, albumin and IgG showed similar Langmuir type pattern onto all test surfaces. On B-PEO4K surfaces, fibrinogen adsorption kinetics demonstrated 'Vroman effect'. The Biomer and B-PEO4K grafts occluded within 1 month, while HEMA-st grafts were patent for over 3 months. Biomer and B-PEO4K showed thick multilayers of adsorbed proteins, and the thickness increased with implantation periods and the composition altered with time. In contrast, HEMA-st showed a monolayer-like adsorbed protein pattern, and the composition and thickness were consistent regardless of implantation time including in vitro short-time experiments, which may attribute to less conformational change of adsorbed proteins on HEMA-st surfaces. In terms of nonthrombogenicity, the stable monolayer-like adsorbed protein layer on HEMA-st surfaces exhibited improved blood compatibility over thick multilayered adsorbed proteins on Biomer and B-PEO4K surfaces.     

In vivo protein adsorption on polymers: visualization of adsorbed proteins on vascular implants in dogs

The absorption of plasma proteins is an important event at the blood-material interface, and strongly affects subsequent cellular interaction and thrombus formation. Although considerable efforts have been expended to elucidate the mechanism of protein adsorption and the role of absorbed protein layer at the blood-material interface, there has been little knowledge of how the initial adsorbed proteins are maintained or changed in a time-variant process in in vivo long-term implantation. In this study, we described detailed analyses concerning the characterization of adsorbed proteins on HEMA-styrene block copolymer surfaces (HEMA-st) and poly(ethylene oxide)(PEO) grafted Biomer® (B-PE04K) for in vivo long-term canine vascular graft implants as well as in vitro short-term experiments. Biomer vascular grafts (6 mm I.D., 7 cm in length) were fabricated by a dip coating and the luminal surface was modified with PEO grafting, HEMA-st coating, or Biomer coating (control). These surface modified grafts were recirculated for different time intervals (5, 15, 30, 60 and 120 min) using citrated canine whole blood. The grafts were then implanted in the abdominal aortas of dogs and evaluated for graft patency and protein adsorption. The adsorbed proteins (albumin, IgG and fibrinogen) were quantified using an in situ radioimmunoassay. Surface protein layer thickness was measured by transmission electron microscopy (TEM). Visualization of absorbed plasma proteins (albumin, IgG and fibrinogen) was performed with TEM using an immunoperoxidase double antibody technique. In in vitro recirculation systems, albumin and IgG showed similar Langmuir type pattern onto all test surfaces. On B-PEO4K surfaces, fibrinogen adsorption kinetics demonstrated 'Vroman effect'. The Biomer and B-PE04K grafts occluded within 1 month, while HEMA-st grafts were patent for over 3 months. Biomer and B-PE04K showed thick multilayers of adsorbed proteins, and the thickness increased with implantation periods and the composition altered with time. In contrast, HEMA-st showed a monolayer-like adsorbed protein pattern, and the composition and thickness were consistent regardless of implantation time including in vitro short-time experiments, which may attribute to less conformational change of adsorbed proteins on HEMA-st surfaces. In terms of nonthrombogenicity, the stable monolayer-like adsorbed protein layer on HEMA-st surfaces exhibited improved blood compatibility over thick multilayered adsorbed proteins on Biomer and B-PE04K surfaces.     

Preparation of double-raschel knitted silk vascular grafts and evaluation of short-term function in a rat abdominal aorta

Silk fibroin fiber has a long history of use in sutures because of its high strength and toughness. In the work reported in this paper, small-diameter vascular grafts 1.5 mm in diameter and 10 mm in length were prepared by coating a double-raschel knitted silk fiber graft with silk fibroin aqueous solution containing poly(ethylene glycol diglycidyl ether) as a cross-linking agent. The most important character of silk fibroin graft is remodeling, which is never observed for polyester fiber or expanded polytetrafluoroethylene grafts. The double-raschel knitted silk fiber graft with coating has sufficient physical strength and protects the ladder from the end in the implantation process. The coating also gives protection against leakage of blood from the graft, and elasticity to the graft. Eight weeks after implantation of the grafts in rat abdominal aorta, early formation of thrombosis was avoided.     

The performance of a small-calibre graft for vascular reconstructions in a senescent sheep model

There is an acute clinical need for small-calibre (<6 mm) vascular grafts for surgery. The aim of this study was to evaluate the long-term performance of a small-calibre graft produced from a nanocomposite biomaterial, polyhedral oligomeric silsesquioxane poly(carbonate-urea)urethane (POSS-PCU), in a large animal model following Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP) protocols. Grafts were characterised and implanted into the left carotid artery (LCA) of senescent sheep (n = 11) for a period of 9 months. In vivo compliance and blood flow rates were measured using ultrasound wall tracking software and a Transonic flow meter. Graft patency and degree of intimal hyperplasia (IH) were examined at the study end point. Seven of the POSS-PCU grafts were free from thrombosis, IH, calcification and aneurysmal dilation, with 4 occluding within 14 days. All of the ePTFE controls (n = 4) were found to be occluded by day 32. The lumen of the patent POSS-PCU grafts was free from any cellular deposits, whilst perigraft tissue could be seen to be infiltrating into the body of the graft from the adventitia. No significant differences were detected between the blood flow rates (p = 0.3693) and compliance (p = 0.9706) of the POSS-PCU grafts and the native artery, either post-operatively or after 9 months implantation. Small-calibre vascular grafts produced from POSS-PCU offer a viable option for the clinical use in revascularisation procedures with a patency rate of 64%.     

Time course of the regression of intimal hyperplasia in experimental vein grafts.

A previous study in which vein grafts were removed from the arterial circulation and reimplanted into the venous circulation of the same animal demonstrated regression of vein graft intimal hyperplasia and medial thickening within 14 days. The present study was designed to characterize the kinetics of the morphological and ultrastructural changes over this 14-day period. Twenty-one male New Zealand White rabbits received a reversed vein interposition bypass graft of the right common carotid artery. Fourteen days after the procedure, 21 vein grafts were isolated, removed, and reimplanted into the contralateral external jugular venous system as veno-venous interposition bypass grafts (reversal grafts). The grafts were harvested at 60 minutes, 1 day, 3 days, 5 days, 7 days, and 14 days after reversal. Before insertion into the venous circulation, the vein graft had a confluent endothelial cell surface with multiple layers of smooth muscle cells representing intimal hyperplasia. After 1 hour, the reversal graft retained an intact endothelial cell layer with no evidence of tissue edema or cellular disruption. By 24 hours, there were a few blood cells on the endothelial cell surface. There was no inflammatory infiltrate seen in the subendothelium, and the smooth muscle cells were unaltered. At 3 days, the endothelial cell lining remained intact with no polymorphonucleocytes in the subendothelium or within the graft wall. Underlying smooth muscle cells at this time were noted to contain cytoplasmic vacuoles. At 5 days, there were no inflammatory cells seen on the surface or within the vein graft wall, but many of the underlying smooth muscle cells within the intimal hyperplasia were noted to be fragmented and to have clumping of chromatin. After 7 days, the endothelial cells remained intact and there was widespread evidence of apoptosis beneath the subendothelium with highly fragmented smooth muscle cells, some of which were histologically in the process of breaking up. At 14 days, the grafts retained uniform endothelial cell surfaces. Most of the smooth muscle cells that composed the intimal hyperplasia seen before implantation as a reversal graft were gone. Areas of newly laid down collagen could be observed. There were no acute inflammatory cells but for some mast cells seen in the graft wall. This study demonstrates that in this model, regression of intimal hyperplasia was associated with apoptosis of the smooth muscle cells and the deposition of collagen. There was no evidence that this process is mediated by an acute inflammatory response. Regression therefore appears to be due to induction of smooth muscle cell apoptosis by either a reduction in pressure or flow or a combination of both factors. The findings will enable a systematic cellular and molecular analysis of the biology of regression, which may afford clues to better understand the biology of the developing intimal hyperplasia.