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Neovascularization of Prosthetic Vascular Grafts. Quantitative Analysis of Angiogenesis and Microhemodynamics by Means of Intravital Microscopy M. D. Menger', F. Hammersetr . P. Walter 1, and K. Messmer? 3

Dept. ofGeneral Surgery. University of Saarland. Humburg, FIlG Dept. ofAnatomy. Technical University Munich, Munich . FRG Dept. of Experimental Surgery. Universityof Heidelberg, Heidelberg. FRG

Summa r)' Neovascularizatio n of prosthetic vascular graft s seems to play an important role in the prevention of early graft failure due to infection or thrombotic occlusion. The process of angiogenesis a nd neovascula rization was a nalyzed for three different prost heti c vascula r grafts (PTfE , Dacron double microvelour and gelatin-coated Dacron doubl e microvelour} in vivo by means of'fluorescence microscopy . Under Nembutal a nesthesia (50 mg/kg B\VI Syrian golde n hamsters were fitted with a do rsal skinfold chamber. which contain s the cuta neous skeletal muscle as well as subcuta neous tissu e, and allows for quantitat ive analys is of the microcirculati on for a prolonged period of time. In eac h chamber one piece (1mm") of all thre e va scular grafts was impla nted . Five days a fter impla ntation neovascularization was ascertained in 9/11 (coated ) a nd 8/ 11 (non-coated) Dacron grafts , while only 4/11 PTFE impla nts revea led new microvcssels . On day 10 the density of newly-formed microvessels was significan tly higher (p < O.OOll in Dacron grafts (234.3 ± 31.2 ern" a nd 238.9 ± 4 1.3 ern" resp ectively) as compared to PTFE implants (154.9 ± 30.4 cm'). In addi tion, Dacro n grafts revealed a larger neovasc ula rizat lon zone exte nding into the perigraft tissue. 12 days after implantation non-coated Dacro n gra fts were most tightly integrat ed into the perigra ft tissu e. The better neovascula rtzation of Dacron might be due to the high poros ity of the gra ft compa red to low porous PTfE , which revealed insufficient neovascu la rization . :'Jeovaskularisierung von Gef8Sprol hese n: Quantlta ttvc Anal yse der Mikrozirkulalion mlt tel s Vitalmikroskop ie a n eine m tie re xpe r lme ntelle n Modell de s Gold ha mslers Bei rekonstr uktlven gefal3chirurgische n Eingriffen worden heute als Ersatz Itlr grol3ere Arterien vor allem alloplastische Gefaflprothesen aus Polyethylenterephthalat (Dacron) oder Polytetra fluc ret hylen (PTFE) verw endet. Die hauflgste n Frtihkomplikatione n naeh gefal3prot het ischem Ersatz sind die Infektion und der th rombotlsche Versehlul3 des Implanta tes. Als Ursache der Infektion wird cine elngesc hra nkte Vera nkerung der Prothese im Per ttra nspla ntatgewebe durch fehlende Ncovaskularisierung mit Ausbildung von serose r Flussigkelt im Bereich der Grenzfaden zwische n Prothese und Per tgraft angenommen . Fur- den thrombotischen Verschlul3wird das fehle nde

Thorac. cardiovasc. Surgn 38 (1990) 139 145 © Georg Thieme Verlag Stuttgart · NewYork

tra nsmura le Kapillar wachstum mit ma ngelha fter oder fehlender Ausbildung elner Neointima vera ntwortlic h gemacht. Ziel der Studie war . die Neovaskular isier ung der dre i Gefa13prothesen P'TEli.Dacron Doppel-Mikrovelour und gelatinebeschich tetes Dacron Doppel-Mikrovelour quan tltativ zu a nalysieren. Als Modell wurde die Ruckenha utkammer des Syrischen Goldha msters (Implant ation unter Nembutalanas theste, 50 mgt kg KG i. p.I verw end et. welche qua ntitat ive Analysen der Mikrozlrkulatic n mittels Video-Vitalml kroskopie-Sca nning-Technik erlau bt. ln jede Kamm cr wurden jewells ca. 1 mm! grol3e Stucke de r drei unters chiedlichen Prothescn impla nticrt. Punf Tage naeh Implantation konnt e bei neu n unbeschlchteten und acht bcschichteten von jeweils 11 Dacronimpla nta tion cine begtnnende Xeovaskulartslerung nachgewiesen werden, wah rend zu diesem Zeitpunkt ledlgtlch vier der 11 PTFEImpla ntate neugebildete Mtkrogefabe aufwlese n. Die funkuonolle Gefa bdtchte dcr Neovaskula ns lerung im Perigraft wa r 10 Tage nach Impla ntation bei Dacronimplan taten (234.3 ± 31.2 em" bzw. 238 ,9 ± 41.3 ern") sigmflkant boh er Ip < 0.0011 gegcnubcr PTf E-lmpla ntaten (154,9 ± 30,4 cm'). Hierbci bewir kten Dacronimp lanta te cine grotlerc maximale Neovaskularisi erungsbreite ins Peritra nsplantatgewebe. 12 Tage na ch Impla nta tion zeigten unbesc hich tete Dacronimplantate die beste Verankerung im Perigraft sowle tra ns murales Kapilla rwachstum. Unbcschlchtet es Dacron Doppel-Mikrovelcur erlaubt. wohl bedingt du rch die hohe wand porosltat und Aufra nkung der Prothesenwand du rcb senkrecht ein gearbcitete Schlingcn. cine fruhzeiug e Neovaskula risierung mit hohe r Gefafldichte. tra nsmural cr Kapillare insp rossung und fester Verankeru ng der Prothese im Peritr ansplan tatgcwebe. Gelat inebeschichtetes Dacron Doppcl-Mikrovelour . welches im klinischen Gebrau ch wie au ch PTFE kein Preclott ing erfordert. la 13t cine iihnlich gunsuge Neovaskulartsterung im Pcntra nspla ntat gewebe zu. ohn e jedoch eine vergleichba re tr an smurale Kap illareinsprossu ng aufzuweisen. PTFE dagegen . wohl aufgrund der geringen Wan dporengrOBe , wird nur wenl g von Mikrogefaflen vaskulari siert und daher nicht ins Peritra nsplan ta tgewcbe lntegr len. Key word s Prosth etic vascular grafts - Neovascula rtzauo n - Intrav ital microscopy - Hamster

Received for Publi cation: December 11.1 989

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lvl. D. Menger, F llammersen. P. Walle r, and K. Mess mer

71lOra c. cardiovas c. S urgn 38 (l 990j

Fig. 1

Intr odu cti on Progr ess in modern vascula r surgery has been greatly accelerated by th e development (42) an d improvem ent (12, 18, 34) of a rt eri al pro stheses for both re placement an d bypass procedur es . However. early graft failure d ue to infection (23, 25, 30) or thrombotic occlusio n (1 , 6, 30) is the most se rious com plication in reconstr uctive vascular surge ry. Insufficient integr ati on of the graft int o the surrounding tissu e du e to ina dequa te neov as cularization is discussed as ca use for perigra ft sero ma and subseq ue nt infection (5 , 32). Furthermore, deficien t transmur a l ingrowth of capilla ries is tho ught to be responsi ble for thrombotic graft occlusio n du e to an imp aired development ofn eoi ntimal coverage (19, 26). Ade quate neovascula rization seems to play an importa nt role in t he ea rly healing process of a rte rial prostheses (11 , 15. 20. 221, In recent years. different materials for prosthetic va scula r grafti ng have bee n int rod uced. Bioprost heses (Artegra ft, Joh nso n and Johnson , USA; Soleogra ft, Soleo Basle Ltd .. Birsfelden , Switzerland), biosyntheti c pr ostheses (Omnillow , Bio Nova , Melbou rne , AUS) and synthetical vascular grafts (PTFE, W . L. Gore , Flagstaff, AZ, USA; Dacr on, Meadox Med icals. Oaklan d, NJ , USA; Bra un Melsunge n , Melsungen , FRG) a re availab le and supposed to pr esent bette r surgica l handling and im proved hea ling conditions. In clinica l pra ctive polytetr aflu or ethylene (PTFE) and polyethy lene te rephthalate (Dacron) are st ill th e most fre quently used ma terials for a rteria l grafting. Th e aim of th e presen t study was th erefo re to quan tify the process ofne ovas cularization of three diffe rent pro sthetic vasc ular grafts, i. e. PTFE, knitted Dacron doub le micro velour . an d gelatin-coated Dacro n dou ble micro velour.

Ma terial and Meth od s Mod el The studies were carried out in Syrian golden hamsters, equ ipped with a dorsal skinfold cha mber. allowing intr avital microscopy of the microcirculation in skeletal muscle a nd skin in the awake a nima l over a prolonged per iod of time (14). In 15 a nimals (age 6- 8 weeks. 60- 80 g BW) the dorsal skin fold cha mber a nd a per ma nen t venou s catheter were implanted as descri bed previously by Hndrich et al. ( 3). Briefly, under Nembutal an esthesia (50 mg/kg BW i. p.I the an imals a re fitted with two symmet rical teflon-coated aluminum frames , positioned on the dorsal skin fold. thereby sa ndwichi ng an extended double layer of skin. One of these layers is completely removed in a circular area of approximate ly 15 mm in diam eter , and the rema ining layer , containing skeleta l muscle and subcuta neous tissue, is covered with a removable cover slip, incorporated in one of the a luminum fram es. A per mane nt ven ous cat heter is passed from the do rsal to the ventra l side of the neck and placed into the jugula r vein.

Vascular grafts The following three grafts ,..'ere used to study neovascularization: PTFE (W. L. Gore , FlagstafT, AZ, USA) with an internoda l distan ce of 30 JLm , knitted Dacron double microvelour (Braun Melsu ngen. Mclsungen. FRG) with a n intern odal dista nce of 212 c.m. revealin g a porosity of 1900 rnl/rntn/crn". an d gelatin-coated Dacron double mlcrovelour (porosity before gelatin-coating of 1900 mil min/ern", Braun Mclsungcn. Melsungen . FRG). By gelatin-coati ng the porosity of the gra ft is reduced to a ml/mi n/cm " at the time of impla ntation, approaching the porosity of1900 ml/min/cm! during th e process of graft healing due to resorption of the gelatin.

Hamster dor-

sal skinfoldchamber I hourafter implantation of piecesof PTfE(Pl. non-coated Dacron doublemicrovelour (D) and getatm-coated Dacrondouble merevelour (GO) grafts. Bar represents 1.5 mm: magn. x 10

Experimental prot ocol In 15 an imals a piece of 1 mm! of each of the three vascular gra fts w as impla nted into the skinfold cha mbe r (Fig. 1). The process of

an giogen esis and neova scula rizatlc n was followed in 11 animals da ily by mea ns of intrav ital microscopy using mag nilication ofx 64. On day 10 the functi onal density of the newly formed mlcrovessels Il.c. the number of red -cell-perfused mtcrovessels per area) and the maximal extension ofthe neovascularizatlon zone into the perigraft tissue w ere anal yzed by mean s of intravita l fluore scence microscopy. video techniques, a nd a computer assisted image analysis system (35). Contras t enhancement for fluorescen ce microscopy was achieved by intravenous ap plication of FITC-Dextra n 150 000 (Sigma, St. Louis, Mal.

Measuremen t ofdynamic breaking strength In the 11 a nimals the integrati on of the grafts into the perigraft tissue was assessed on da y 12 by measurem ent of the dyna mic breaki ng strength. The grafts were fixed at their 4 edges with 8- 0 prolene sut ures and constant pulling with I cN/s ec was employed. The force necessary to tea r the graft out of the per igraft tissue ind icated the dyna mic breaking strength (cN/ mm2 ) .

Histological examinations Furt her 4 animal s w ere sacrifled on day 12 and the entire skinfold prep a rat ions were fixed together with the vascula r grafts by superfusion with 2.5 % gluta raldehyde in 100 mmollL Na-cacodylat e buffer (pIl 7A ) for 30 minu tes. The tissue was then ca refully excised and put in the same fres h fixat ive for a nother 24 hours at 4 °C, before small pieces were dissected under a ste reo microscope. These specimens were then routin ely pr ocessed for tran smission electron microscopy, employing a Zeiss-EM lOA microscope operated at 60 KV. For light microscopy sernnhin sections (0.5- 1J,tm) sta ined with meth yleneblue-azur II were used.

S tatistical analysis Values were tested for norma l dist ribution and eithe r a n a nalysis of variance and Stude nt t-test accompanied by Bonferroni prob abilities (nor mal distribu tion) or the Kruskal-walhs a nalvsis (non normal distribu tion ) was performed to test for significant difference s between the groups. Differences w ere cons idered significant at the p < 0.05 level.

Results

intra oital microscopy First signs of neo vascularizat ion were observed in the peri graft tissu e betw een days 2 and 4 a fter im plantation, and

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140

Neooascutarizauon of Prosthetic Vascular Grafts

the y consisted of both petechial bleed ings and a n inflammat ory reaction. i.e . dilatation and tortuosity of the host's skeleta l muscl e capillaries (Fig. zal, Subs equ ently. ca pillary sp routs were see n to-originate from the venula r segments of the cuta neous skeleta l muscle ca pilla ries. During the following days. these sprouts created a microvascula r network the meshes of which vari ed in width. This was accomp anied by the disappearance of the first genera tion of petechiae. while new ones occurred at a far ther dista nce , serving as a n Indlcator for future a reas of neova scula rizati on (Fig. 2b). Th is

Thorae. eardiol'asc. Surgn 38 (1990)

141

of 11 PTFE imp lant s. On day 10 all of the Dacron grafts (n "" 22) revealed new vessel formation in the perigr aft tissue. wh ereas this phenomenon was observed in only 9 ofth e 11 PTFE grafts (Fig. 31. The most striking difference. however. was that in th e knitted Dacron prostheses the newly form ed microvessels penetrated into the grafts them selves (more pr onoun ced in the non-coa ted vs. the gelatin-coated variety: Pig. 4, 8, 9), whe reas in PTFE impla nts neovascula riza tion was restri cted to the perigraft a reas (Figs. 5. 7). Within the latt er

number of vascular graflS 10

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Fig. 2a Gelatin-coatedDacron doublemcr ovelour graftonday3 after«norenteton . Notethepetechial bleedings 1-)andtheinflammatoryreactionIi.e. dilatationand tortuosity of theskeletalmusclemcrovessels: ..-)withinthe perigraft tissue. Bar represents 500j..l.m; magn. x 62

25

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PTFE

max . wid th of neov ascularizeticn

Fig.3 Timecourseof neovesculadzation (number of vascularizedgrafts). functional densityof mcrovessels(day 10).maximal width of theneovasculanzationzone(day 10)and dynamicbreakingstrength (day 12)in non-coatedDacron doublemlcrovelour (D . 01.gelatin-coatedDacrondouble rmcrovelour (0 , GI OJ and PTFE I-j grafts. Mean ± SO. l ·way ANOI/A, Student t-test. • p < 0.05. " p < 0.Ql, ••• p < 0.001.as compared to PTFE·group

functional density of microvessels was significa ntly (p < 0.001 ) higher in the Dacron tha n in the PTFE gra fts (Fig. 3. 6). a nd the zo ne of neovascularization was consisten tly wider in Dacron as comp a red to PTFE imp lants (Fig. 3). In addition. noncoated Dacron grafts exhi bited the greatest dyna mic break ing strength on da y 12 after impla ntation (Fig. 31. His tology Fig. 2b representsthe same graft on day 7 afterimplantation. Notethenewly formedcapillaries, originating fromthemicrovasculatureof theperigraft tissue (*). Thepetechial bleedings within theperigrafttissuehave disappeared while newbleedings (..-)indicate thearea of further neovascurarlzation; Bar represents 500 j..l.m; magn x 62

also allowed an ea rly estimat e wheth er the newly formed vessels will penetrat e int o the gra ft itself or if they will be restricted to th e perigr aft tiss ue , On da y 5 afte r implan ta tion 9 out of 11 gelatin- coa ted Dacron grafts a nd 8 of the non-coat ed Dacron grafts showed pe rigraft neovascularizati on. contra ry to only of from a total

Light microsco py of plastic semith in sections corrobora ted the vital micros copic findings : Even on day 12 after imp lanta tion the PTFE gra fts showed newly form ed microvessels exclusively in a very narrow perigraft zone (Fig. 7). This was mainly loca ted at the lateral as pects ofthe imp lant. wh ereas its bottom was immediately attached to the cuta neous skeleta l muscl e fibers. wh ere neither cellular nor vascula r proliferati on was seen . By contrast. the Dacron grafts exhibited a pr omine nt cellula r and vascular reaction also along the attachment site of the impla nts (the non-coated variety more pronoun ced

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- - PT FE

AI. D. M enger. F. ttammersen. P. Wall er. and K. Messmer

Thom e. cardiot'asc. Sl1rgn 38 (1990)

Fig.4a

Fig.4b

Fig. 4 Non-coatedDacrondoublemicrcvelour graftbeing completelyneovascularizedon day 10after implantation(Fig. 4a). Noticethe dense networkof newly formed rmcrovesseis (-+ ), originating fromthe perigrafttissue1*1. and penetrating into theintersticesof thegraftmatenatt s-: Fig.4b}.To facilitate orientation identicalsymbols (*1mark identical vessels. Barsrepresent 500 Iotm and 200 Iotm; magn. x 62 and x 140, resoecnvefy

Fig. Sa

Fig. 5b

Fig. 5 PTFEimplant onday 10 afterimplantation.demonstrating insufficient neovascutareatton(Fig. Sa). Thenewly formed rmcrovessels (-- I,originating fromthepengraft tissue1*),aregrowing onlyalongthe outer perimeterof the graft(Fig.Sa,bl, whileanactual capillaryingrowthis absent(Fig.5bl. Bars represent 200 Iotm; magn. x 75 and x 140, respectively

Fig. 6 Non-coatedDacron double mcrovelour grafton day 10 afterimplantanon showing a dense networkof newly formed microvessels(Fig.6a1.l ntravital fluorescence microscopy,contrast enhancement by meansof Flle·Dextran 150 000 tv. Barrepresents loo lotm; magn x 285

Fig.6b demonstrates onlyfewcapillarysprouts ina PTFEgraft 10 daysafter implantation; Intfa'o'ita!fluorescence microscopy.contrast enhancement by means of FIlC Dextran 150000 i.v: Bar represents 100 Iotm; magn. x 285

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Neooascularizauon of Prosth etic Vascular Grafts

Thorac. cardioL'asc. Surgn 38 (1990)

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,.

Fig. 7 Sermtbm plastic sectionof two thirds of a PTFE graft 12 daysafter implantationinto a hamster skintoldchamber.Granulationtissue togetherwith newlyformed vessels is predominantlyfound at the lateral aspects (-I of the implant. while rtsbottom is closely attachedto thecutaneousskeletal muscle fibers("'). Notice theabsenceof ingrowthof vascularized granulationtissue Into thegraft andthe very incompleteovergrowth 01the freesurface 1*1of the implant. F- fat cells: bar corresponds to 100u rn, magn. x 200

than the gelatin-coated graft; Figs. 8, 9). which expanded over the later al as pects of the implants and tended to cover even their free sur faces. In addition. this area of neovas cularization was significantly wider than tha t around the PTFE gra fts (Fig. 7), and it is bro ader along the lateral as pects of the implants. When comparing the two types of Dacron grafts it becomes evident that both the ingrowth of microvessels an d of gra nulation tissue is far more pronounced in the noncoated vari ety, wher e microvessels and a highly cellular gra nulation tissue rea ch dee ply into the prosthetic material (Figs. 8, 9). Her e the newly forme d connective tissue cells do not merely penetr ate between and closely su rro und the synth etic fibrils. but they also transfo rm their original circular profiles into irr egular triangl es (Fig. 8)_By contrast, in the gelatin -coated grafts granulation tissue cells have grown rather deeply into the implant. whe reas newly form ed vessels main ly exist at this time (12 days after implantation) within the highly cellular perigraft tissue (Fig. 9). Discu ssion The treatment of peripheral arte riosclerosis by vascu lar reconstruction with prosthetic vascular grafts represents one ofthe significant advances in surgery during the last five decades. However, since ea rly infection and thrombotic occlusion continue to be a problem for vascular surgeons (1, 6. 25. 30), numerous investigations have aimed thei r studies at alleviating these disadvantages (2. 3. 20). Adequa te healing of vasc ular prosthesis with development of a complete neointimal surface and tight integration into the perigraft tissue seems to play a major role in the prevention of early graft failure. It is well known that vascular grafts are covered by endothelial cells ingrowing as a continuous sheet from th e remaining vessels across the anastomosis and along parts of the grafts (1 O. 15. 16). However. th is process is limited to the

Fig.8 Sermthst plastic sectionof a non-coatedDacrongraft 12 daysafter implantation into a hamster skinfold chamber. Ahighly cellular and vascularized granulationtissue1*1 hasdeveloped alongthe bottom and lateralaspect of the graft(delineated bythefat cells: F)andhasalso penetrated deeply intothe graft itseU. Therebythe synthetic fibrils of thisfabric arenotonly pushedwidelyapart but theyare alsotransformed into irregulartriangular profiles(circled)the surfacesof whichare covered by closelyattached cells. Bar correspondsto 1001J.m; magn. x 200

..,

,. .1 .

,.

\ '/

Fig.9 Semrthin plastic section of agelatin-coatedDacrongraft 12 daysafter implantation into a hamster skinfold chamber.Ahighlycellular andvascularized granulationtissue (* Jislocated between the cutaneous muscle layer 1-) and the graft, fromwhich at tt ns time merelythe cellularcomponents have emigrated into the knitted n ucrcvelour graft.Arrowheads ("'I indicate nucleiof invaded cells. Bar represents 100 1J.m; magn. x 320

edges of the graft and hence neointimal coverage rema ins incomplete, pa rticularly at luminal sites distant from the anas tomoses (4, 15, 32). Several investigators have suggested that endothelial cells can circulate in the blood an d settle onto the luminal surface of the gra ft (1 7). Alternatively. the endothelium might originate from capillaries growing through the graft matrix from outside (11, 15. 20, 22). Tra nsmu ra l capillary Ingrowth as a means for obtain ing graft coverage was first suggested by Florey et al. OS) 25 yea rs ago in a study on endotheli al growth in short Dacron grafts inse rted into baboon aortas. Later on, Clowes and coworkers (1) reported that the mechanisms of endothelial coverage of

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M. D. M enge r. F. Hammer sen. P. Walt er. an d K. Mes smer

S u rgn 38 (1990)

PTFE surfaces can be tremendo usly altered by chang ing the porosity of the graft. When the average internodal distanc e was increased from 30 /lm to 60 /l a rap id and complete endot helial coverage of PTFE grafts was observed . In addition. using the microcorrosion cast techniq ue transmural vascularization could be demonstrated in PTFE implants with a fibril length between 60 /lm and 90 s m. revealing concom itant ly complete endothelialization (21). These experimen ts have provided strong suppo rt for the hypothesis that capillaries do penetrate the wall ofthe grafts and serve as sources for the luminal endothelium. In the present study. angiogenesis and neovascular izatlon of different vascular graft materials wer e demonstrated for the first time in vivo; our stud ies revealed that a network of microvessels develops, which originates from the capillaries of the perigraft tissue. The porosity of the graft seems to deter mine whether successful capillary ingrowth takes place (8, 11, 22). In our study. Dacron grafts , due to their high porosity, showed a dense microvascular network with a large number of microvessels piercing into the interstices of the graft. In PTFE implants a low density network of microvessels surro unded the graft and penetration of microvessels into the graft was never encountered . These findings are in accordanc e with the observations of Rah/fand coworkers (26), who showed that the healing process of vascular grafts is improved in mater ials of high poros ity, particu larly during the phase of resorption, when proliferation of histiocytes and fibroblastic cells as well as of capillaries into the grafts' interstices can be observed. In contrast. in graft materials with low porosity limited invasion of vascularized granu lation tissue was present (26). In addition. Rainwater et al. (27) have demonstrate d in PTFE grafts (20 -30/lm intern odal distance). which were placed in the infrar enal aorta of goats. that fibroblasts and collagen had penetrated the graft. while no capillary ingrowt h was observed . although arterioles and capillaries were present in the perigraft connective tissue. Histological examinations of biopsy specimens obtained from PTFE grafts revealed ra re ingrowth of host connective tissue. absence of neovascularization and limited neointima l proliferation (7). However, in Dacron gra fts Math isen et al. (24) have shown that rapid thr oughwall healing takes place in warp-knit. externally velour ed prostheses over the entire porosity range from 286 ml/crnj/ min to 2036 ml/cmj/min in the canine descending aorta , while lower porosities will not permit through-wall healing (9,28, 34). In the present stud y non-coated Dacron double microvelour revealed the tightest integration into the perigraft tissue . By coating this material with gelatin the attachment to the perigraft was found reduced at day 12 after implantation. PTFE, due to its low porosity, revealed insufficient perigraft integration. Ingrowth of connective tissue of variable cellularity into the interstices of the prostheti c weave results in stro nger adhesion between the graft and its surrounding tissue (26). In porous knitted arterial prost heses with an externa l velour surface outer capsule adherence has been superior to that seen in convent ional gra fts having smoot h oute r walls. The stab ilization provided to the outer caps ule app ears important for the inner wall healing (29). Tightly woven materials with low porosity, such as Teflon or a variet y of other materials. are prone to healing complications and per igraft accumulat ion of se rum. which

can lead to devitalization oft he inner capsular blood supply, finally causing complete degener ation and sloughing of the inner capsule (32). Harrison and Davelos (19) demonstrated the importance of these two factors , i. e. neointimal coverage and integration of the graft into the perigraft tissu e, because the incidence of throm botic occlusion can be lowered from 38 % in tightly woven teflon grafts to 14 % in knitted porous teflo n grafts . In general, vascular prostheses of highly porous mate rial will heal better tha n less porous grafts, due to early neovascularization, development of a dense microvascular network and improvement of graft integration into the perigraft tissue.

References 1

2

3

4

5 6

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A llen. B. T.. an d C.J. Math ias: Platelet dep osition on vasc ular grafts. The accur a cy of in vivo qu an titation and the significa nce of in vivo platelet reactivity. Ann. Surg. 203 (1986) 3 18-328 Ben Sttmone. 5.. R. Guidoin. Y. M erhi, M. W. King, D. Domurodo. an d M.-F. Siqot-Luizo rd. In vivo eva luation of polyester a rte r ial grafts coated with a lbumin: The ro le a nd importa nce of cross, linking agents. Eur. Sur g. Rcs. 20 (1988) 66-74 Benoenistu. A. I.. G. Tannen baum . T. N. Ahlborn. C. L. Fox. S. Moda k. L. Sampam. K. Reemtsma. and R. Nou'ygrod: Con trol of p rosth etic ba cterial infection : Evalua tion of a n eas ily incorp orated. tightly boun d, silver a ntib iotic PTFE graft. J. Surg . Res. 44 (19 881 1- 7 Berger. K.. L. R. Sauv age, A. M. Rao, an d S. J. Wood: Hea ling of a rter ial prost heses in man : Its incompleteness . Ann . Surg. 175 (1972) 118-12 7 Borrero. E.. an d W. Doscher: Chro nic perigraft se romas in PTFE gra fts. J. Car dtovasc . Surg. 29 (1988) 46-49 Callow. A. D.: Curre nt sta tus of vascu lar grafts. Surg. Clin. North Am. 62 (1982l 501-513 Camilleri. 1. P.. V. N. Phat. P. Brune ool. V. Tricottet. A. Balaton. J.N Hessinger. a nd J.-M. Cormier: Surface he aling a nd h istologic ma turation of pat ent polytetralluoroethylene grafts im plan ted in pat ients for up to 60 month s. Arc h. Path ol. Lab. Med. 109 (19 85 )

833-83 7 Campbell. C. D.. D. Goldfarb. andR. Rodney : A small a rte rial substitute: Expa nd ed microporou s polytetra fluoroethylcne. Paten cy vs. porosity. Ann. Surg. 182 (1975) 138 - 143 \I Cenqu. M.. L. R. Sauv age. a nd K. E. Berger: Effects of compliance alteration on hea ling of a porou s Dacron prosthes is in the th oracic aorta of the dog . Surg. Gyne col. Obstet. 158 (1984) 145- 151 10 Clowes. A. U~ , A. M. Gown, S. R. Hanson, a nd ,\I. A. Reidy : mecha nis ms of arterial graft failure . 1. Role of cellular prolifer ation in ea rly healing of PTFE prostheses. Am. J. Pathol. 118 (1985 ) 43 - 5411 Clowes. A. ~v. , T. R. Kirkma n, a nd R. A . Reidy : Mech an ism s of arteria l graft hea ling. Rapid transmural cap illary ingrow th p rovides a source of intimal en dot he lium an d smooth muscle in porou s PTFE pr ostheses. Am . J. Pathol. 123 (1986 ) 220-230 12 Crawford. E. S.. 0. Creech j r.. D. A. Cooley. a nd AI. E. DeBakey: Treatment of a rte rioscle rotic occlusive disease oflowe r extrem ities by excision and graft replacement or bypass. Surgery 38 (1955 ) 981-992 13 Endrich. B.• K. A sais hi. A. Goetz. a nd K. Mes smer: Technica l report - A new chamber tech nique for microvascular st udies in una nesthet ized ham sters. Res. Exp. Med. 177 (1980 1125- 134 I ~ Endrich. B; a nd K. Messmer: Quantitative a na lysis of the microcirculation in the awa ke an ima l. In: Olszewski, W. Ied.]: Ha nd book of micros u rgery . Miam i, Fl, USA: CRC Press 198 4, pp. 79- 105 IS Plorey, I/. iv, S. J . Greer. J. C. F. Poole. and N. T Werthessen: The deve lopment of the pse udoin tima lining fabric gra fts of the ao rta. Br. J. Exp. Path ol. 43 (1962 ) 655-660 16 Ghidoni. J. J.. D. Liotta, C. W. lI aff. J. G. Adams. A. Lecnter. At. Bamanueva. R. M. O'Nea l. an d lH. E. IJeBakey: lIea ling of pseudoint imas in velour-lined. imperme able a rterial pro sthesis . Am. J. Pathol. 53 (1968) 375-390 S

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Souroqe. L. R.. K. Berger. S. 1. lr ood: lnters pectes healing of porous arterial prostheses. Arch . Surg. 109 (1974)698-705 Soum qe. L R.. K. Berger. S. J. l\-'ood, Y. Na kagawa. and P, B. Mansfi eld: An experimen tal velour surface for porous arterial prostheses. Surgery 70 (1971) 940-953 Schuma n, E. S., G. F. Gross, J. F. /l ay es, and B. A. St andage: Longter m patency of polytetra fluoroethylene graft fistulas. Am. J. Surg. 155119881644-646 Vorhees. A B.}r.• A Joretsk i Ill. and A. H. Blake more: Use of tubes const ructed from vt nycn- ~ 7\ . cloth in bridging art eri al defects. Ann. Surg. 135( 195 21332-336 1\ 'esotoux A .: The healing of arterial pros theses - the state of the a rt. Thorac. Cardtovasc. Surgeon 30 (19821196-208 U'esolofL'ski, S. A.. C C. Fries, K. E. Karlson, .\1. E DeBak ey, and P, ,\'. S au'y er: Porosity: Primary determinant of ultimate fate ofsyntbe tic vascular grafts. Surgery 50 (1961) 91 - 96 and 105-1 06 lfhile, R. A.. E. u: White. and E. L. Hanson: Preliminary report : Evaluation of tiss ue Ingrowt h into experimental Replamineform vascular prostheses. Surgery 79 (1976) 229-232 Zei ntl, 1/.. W R. Tompkins. K. stessmer. and .\ 1. lnt agliett a: Static and dynamic rmcroctrculatoryvld eo image analysis app lied to clinical investigations. Prof. AppLMicrocirc. 11 1198611-1 0

Michael D. xtenqer. M. D. Dept. of General Surgery University of Saarla nd 0 -6650 Homburg/Saar, FRG

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Neovascularization of prosthetic vascular grafts. Quantitative analysis of angiogenesis and microhemodynamics by means of intravital microscopy.

Neovascularization of prosthetic vascular grafts seems to play an important role in the prevention of early graft failure due to infection of thrombot...
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