Development of a symmetric canine abdominal aortic aneurysm model with clinical relevance for endovascular graft studies.

This study was designed to develop a large-animal model to study and validate transluminally placed endovascular grafts and related techniques for treating abdominal aortic aneurysms with minimal trauma. In four dogs, a segment of infrarenal abdominal aorta was dissected and an endarterectomy was performed through an aortotomy to remove the entire intima of this controlled aortic segment. The opening was patched with chemically processed bovine pericardium, and an identical patch was applied after aortotomy of the opposite side of the aorta. Aortic diameter and flow were measured before and after the procedure. Angiograms were obtained just before retrieval. All dogs recovered quickly with no complications. Aortic diameter increased approximately 2.7-fold. Aneurysm size and shape remained stable until the end of the experiments at 4 or 8 weeks. Gross and histologic studies for 4- and 8-week specimens were similar. Factor VIII/von Willebrand factor staining showed complete reendothelialization of the endarterectomized wall, with a moderate degree of intimal hyperplasia. The patch material retained its acellular nature and its surface was covered with thrombus or fibrinous material mixed with blood cells and inflammatory cells. Thus, this model is feasible and suitable for endovascular graft healing studies.

Favorable histologic findings and tensile strength at 14 years in knitted polyester aortofemoral and femoropopliteal grafts in the same patient.

Patent right and left limbs of an aortobifemoral knitted polyester graft and a patent left femoropopliteal graft, both implanted for 14 years, were removed 40 hr postmortem from a 63-year-old man. Healing studies were performed, using routine and immunocytochemistry staining scanning electron microscopy (SEM), and transmission electron microscopy (TEM) on multiple samples taken from sites sufficiently far from the anastomoses to avoid pannus healing. Evaluation by weight-elongation comparison with a fresh graft demonstrated that structural stability and strength were well preserved. Anastomoses were patent with no remarkable intimal hyperplasia. There was no thrombus on the flow surface of either graft. Histologic studies of these grafts revealed uniform through-wall tissue ingrowth and extensive patches of endothelial cells scattered over the flow surface, confirmed by factor VIII, SEM, and TEM. These findings document that long-term stable tensile strength and healing with flow surface endothelialization can be attained with knitted polyester grafts in the human.

Ticlopidine, Alka-Seltzer, or a combination of citric acid with aspirin: effects on platelet aggregation in individuals with an insufficient response to aspirin alone.

Aspirin (ASA) does not effectively lower platelet aggregation in all people. The platelet aggregation (PA) score is an easily used clinical method for measuring the effect in individuals of antiplatelet medications. Fifteen apparently healthy subjects (2 men and 13 women), selected for their resistance to ASA's antiaggregation effect, completed a sequential trial of ticlopidine, Alka-Seltzer, and ASA + citric acid (CTA). Ticlopidine was the strongest aggregation inhibitor and the ASA + CTA combination was more inhibitory than Alka-Seltzer. It was determined that measuring antiaggregation effects of a particular agent in an individual prior to usage would optimize treatment. The PA score methodology provides a means for testing patients prior to antiplatelet therapy for prevention and treatment of the thrombotic complications of vascular disease.

Administration of granulocyte colony-stimulating factor enhances endothelialization and microvessel formation in small-caliber synthetic vascular grafts.

OBJECTIVE: The purpose of this study was to determine whether systemic administration of granulocyte colony-stimulating factor (G-CSF) would promote endothelialization for small-caliber Dacron vascular grafts. METHODS: We implanted 4-mm preclotted Dacron grafts in both carotids of 12 dogs. For a fair comparison, all dogs had a comparable platelet aggregation profile with platelet aggregation scores less than 30. Five dogs served as controls, and the others were given 7-day subcutaneous injections of G-CSF (10 microg/kg per day), starting on the seventh postoperative day. The effect of G-CSF was evaluated by white blood cell count, which showed a 3.7-fold (+/- 2.7-fold) increase at the end of treatment. Grafts were harvested at 4 weeks. All G-CSF grafts were patent, and one control occluded. Endothelial-like cell coverage averaged 80.8% on G-CSF grafts, but only 35.6% for control grafts (P <.0004). With the exclusion of the anastomotic pannus healing factor, the difference in endothelial-like cell coverage was even greater (68.5% vs 9.8%; P <.0001). Immunocytochemical staining and electron microscopy studies demonstrated endothelial cells. Light microscopy also showed that there were more microvessels on and in the G-CSF grafts than in the control grafts. This study suggests that G-CSF can enhance early endothelialization of small-caliber vascular grafts. Further studies to determine the proper dosage and timing are needed before clinical application can be recommended.

Enhanced endothelialization and microvessel formation in polyester grafts seeded with CD34(+) bone marrow cells.

The authors have shown accelerated endothelialization on polyethylene terephthalate (PET) grafts preclotted with autologous bone marrow. Bone marrow cells have a subset of early progenitor cells that express the CD34 antigen on their surfaces. A recent in vitro study has shown that CD34(+) cells can differentiate into endothelial cells. The current study was designed to determine whether CD34(+) progenitor cells would enhance vascular graft healing in a canine model. The authors used composite grafts implanted in the dog's descending thoracic aorta (DTA) for 4 weeks. The 8-mm x 12-cm composite grafts had a 4-cm PET graft in the center and 4-cm standard ePTFE grafts at each end. The entire composite was coated with silicone rubber to make it impervious; thus, the PET segment was shielded from perigraft and pannus ingrowth. There were 5 study grafts and 5 control grafts. On the day before surgery, 120 mL bone marrow was aspirated, and CD34(+) cells were enriched using an immunomagnetic bead technique, yielding an average of 11.4 +/- 5. 3 x 10(6). During surgery, these cells were mixed with venous blood and seeded onto the PET segment of composite study grafts; the control grafts were treated with venous blood only. Hematoxylin and eosin, immunocytochemical, and AgNO(3 )staining demonstrated significant increases of surface endothelialization on the seeded grafts (92% +/- 3.4% vs 26.6% +/- 7.6%; P =.0001) with markedly increased microvessels in the neointima, graft wall, and external area compared with controls. In dogs, CD34(+) cell seeding enhances vascular graft endothelialization; this suggests practical therapeutic applications. (Blood. 2000;95:581-585)

Morphology and histology of human and canine internal thoracic arteries.

BACKGROUND: We evaluated human and canine internal thoracic arteries (ITAs) to determine whether the latter is valid for studies relevant to clinical use. METHODS: We studied 19 human ITAs obtained from 1 female and 14 male victims of recent fatal accidents who had no evidence of cardiovascular disease (mean age = 39+/-19 years; range = 15 to 79 years), and ITAs of 21 randomly-selected mongrel dogs of both sexes, weighing 18-40 kg (average = 24.3+/-5.7 kg). Specimens were fixed in formalin at a controlled pressure of 120 mm Hg, before extensive assessment that included intimal thickening, condition of the internal elastic lamina, and number of medial elastic lamellae and vasa vasorum. RESULTS: The canine morphology and histology were similar to the human ITAs, but there was no intimal hyperplasia, and the media and adventitia were thinner (ITAs of humans older than 40 years had significant increases in medial thickness, as well as in overall length). Morphologically and histologically, the left and right canine ITAs were almost completely the same. CONCLUSIONS: Canine ITAs are valid for bilateral comparative studies and are a useful tissue source and model for clinically-relevant experimental studies.

Accelerated healing of Dacron grafts seeded by preclotting with autologous bone marrow blood.

> Studies have suggested that bone marrow-derived cells in the circulation may have the capacity and potential to endothelialize and heal vascular graft surfaces. We have investigated whether accelerated endothelialization could be achieved for Dacron grafts seeded by preclotting with bone marrow blood (BMB). Five 8 mm x 6 cm Dacron grafts seeded and preclotted with BMB and four controls preclotted with peripheral blood were implanted in the descending thoracic aorta (DTA) of mongrel dogs for 2 and 4 weeks. Two additional BMB DTA grafts were studied for 3 months. Five pairs of BMB and control grafts (4 mm x 6 cm) were bilaterally implanted into the carotids of dogs for 1 week and five pairs for 4 weeks. All grafts remained patent. BMB seeding/preclotting was a simple, effective method to accelerate early graft endothelialization without increasing thrombogenicity. Further studies are needed before clinical application can be recommended.

Clinical and experimental demonstration of complete healing of porous Dacron patch grafts used for closure of the arteriotomy after carotid endarterectomy.

A clinical porous Dacron patch graft used for closure after carotid endarterectomy was explanted 24 hr postmortem during autopsy. There had been no TIAs or stroke postoperatively, and the cause of death was congestive heart failure. The graft had been implanted for 25 months. The specimen had a very clean surface, was completely incorporated by full-wall tissue ingrowth, and the flow surface was covered with well-organized neointima containing endothelial cells and smooth muscle cells, as confirmed by immunological studies. For comparison, animal experiments were performed. In both the clinical and experimental specimens the carotid patches were patent without neointimal compromise of the lumen, and their healing patterns were similar, with endothelium on the flow surface.

A clinical comparison of Dacron patch closure of small-caliber carotids compared with primary closure of large-caliber carotids after endarterectomy.

The objective was to study results of carotid endarterectomies performed between 1975 and 1991, comparing primary closure to Dacron patch closure. This was a retrospective study. Data from patient follow-up by physical examination, chart review, and Duplex study were used. Scan data were obtained in 92 of the primary cases, at a mean of 5 years postoperatively, and in 63 of the patch cases, at a mean of 4.1 years postoperatively. During this period, 269 endarterectomies were closed primarily and 101 were closed with a knitted Dacron patch. Twenty patients in the primary group and nine patients with patch closure were lost to follow-up, which extended for up to 12.5 years, with a mean of 4.7 +/- 3.6 years. No acute closures, infections or aneurysms developed in either group. Perioperative stroke incidence was 4.1 per cent for primary closure and 3.0 per cent for the patch group (P > 0.05). Late stenosis occurred in 17.3 per cent of the primary group and 11.1 per cent of the patch closure group (P > 0.05). Five-year survival was 76.2 per cent in the primary group, compared with 79.2 per cent for patch closure. Late stroke incidence was 2.8 per cent in the primary group and 3.3 per cent in the patch closure group. Results of smaller (< or = 3.5 mm) carotid arteries closed with knitted Dacron patches are equivalent to those of larger carotid arteries closed primarily.

Genetic tracing of arterial graft flow surface endothelialization in allogeneic marrow transplanted dogs.

In order to trace genetically the source of fallout endothelialization on arterial grafts, six beagle dogs with successful autologous bone marrow transplantation received composite tandem aortic grafts with an isolated, totally impervious Dacron graft and a porous Dacron graft for 12 weeks. For impervious segments, five of 12 fresh tissue samples were Factor VIII/von Willebrand factor + (FVIII/vWF) and seven had faint or negative signals; three of the FVIII/vWF + samples had alpha-actin + smooth muscle cells. Polymerase chain reaction (PCR) study showed eight had a pure donor DNA genotype and four had donor/host mixed, with the donor predominant. Of 12 AgNO3-stained samples, 11 showed pure donor type and one had donor/host mixed, with the donor predominant. For porous segments, all 12 fresh samples had positive flow surface FVIII/vWF and alpha-actin cells. PCR showed all these samples and all 12 AgNO3-stained samples had donor/host mixed type, but the host pattern was predominant. Porous graft healing appears to involve both cellular fallout and tissue ingrowth, and bone-marrow-derived cells may be a source for fallout.

Dynamic and comparative vascular graft healing studies using multiple sequential biopsies.

In order to follow the dynamic healing processes of vascular grafts and to minimize the possible animal-to-animal variables involved in study results, we developed a carotid-femoral bypass model with multiple sequential biopsies. After bilateral implantation of 70 cm x 6 mm gelatin-impregnated carotid-femoral bypass grafts in 5 dogs, we biopsied and replaced three 10-cm-long segments of each bypass at 2, 4, and 6 weeks, with final retrieval at 8 weeks after the initial implant. The first surgery and later biopsy procedures were well tolerated with no mortality or morbidity, except for some seroma formation. We observed a dynamic progression of healing processes related to the time course, including perigraft tissue reaction to the graft material and surgical trauma, gradual absorption of the impregnated gelatin, tissue ingrowth into the graft wall, and changes in and healing of the graft surface. Because of the sizeable tissue sample generated from each biopsy, this model also allowed various study approaches to be performed on the same specimen. This experimental model enables study of the continuous dynamic healing processes of the same graft in the same animal, providing the practical advantage of reduction of the number of animals required.

The effect of flow shear stress on endothelialization of impervious Dacron grafts from circulating cells in the arterial and venous systems of the same dog.

The purpose of this report was to study effects of shear force and hemodynamic conditions that influence fallout healing in the arterial and venous systems of the same dog. Knitted Dacron grafts made impervious by a 1.5 mm thick coat of silicone rubber bonded to the external surface were implanted for 4 weeks during the same surgery in the descending thoracic aorta (DTA), abdominal aorta (AA) and inferior vena cava (IVC) of each of five dogs. Flow rates were measured during surgery and shear stresses calculated with the Hagen-Poiseuille formula. Full-wall thickness longitudinal tissue sections were embedded in resin and stained with hematoxylin and eosin for light microscopy, and in paraffin for immunocytochemistry studies with Factor VIII/von Willebrand factor, smooth muscle alpha-actin, collagen IV, laminin, and proliferating cell nuclear antigen. Scanning electron microscopy and transmission electron microscopy studies were also performed. AgNO3 was used to determine percentage of endothelial-like cell coverage on the flow surface. All grafts were patent, without hematoma or seroma. Endothelial-like cell coverage was highest in the IVC grafts and lowest in the DTA. Shear stress and flow velocity were significantly lower in IVC grafts than DTA and AA. Proliferating cell nuclear antigen indicated extensive cellular proliferation in the intima and in the interstices of the inner portion of the graft wall. The degree of fallout healing in knitted Dacron grafts made impervious by an external coat of silicone rubber varies inversely with the sheer force of blood flow in these grafts.

Evidence for circulating bone marrow-derived endothelial cells.

It has been proposed that hematopoietic and endothelial cells are derived from a common cell, the hemangioblast. In this study, we demonstrate that a subset of CD34(+) cells have the capacity to differentiate into endothelial cells in vitro in the presence of basic fibroblast growth factor, insulin-like growth factor-1, and vascular endothelial growth factor. These differentiated endothelial cells are CD34(+), stain for von Willebrand factor (vWF), and incorporate acetylated low-density lipoprotein (LDL). This suggests the possible existence of a bone marrow-derived precursor endothelial cell. To demonstrate this phenomenon in vivo, we used a canine bone marrow transplantation model, in which the marrow cells from the donor and recipient are genetically distinct. Between 6 to 8 months after transplantation, a Dacron graft, made impervious to prevent capillary ingrowth from the surrounding perigraft tissue, was implanted in the descending thoracic aorta. After 12 weeks, the graft was retrieved, and cells with endothelial morphology were identified by silver nitrate staining. Using the di(CA)n and tetranucleotide (GAAA)n repeat polymorphisms to distinguish between the donor and recipient DNA, we observed that only donor alleles were detected in DNA from positively stained cells on the impervious Dacron graft. These results strongly suggest that a subset of CD34+ cells localized in the bone marrow can be mobilized to the peripheral circulation and can colonize endothelial flow surfaces of vascular prostheses.

Effect of skeletonizing dissection on the internal thoracic artery.

BACKGROUND: Skeletonization of the internal thoracic artery (ITA) produces greater length for coronary bypass grafting. We studied the effect of skeletonization on the morphology, histology, and tissue viability of the ITA wall. METHODS: Six mongrel dogs underwent unilateral ITA dissection; the contralateral ITA was the control. Study periods were 3 weeks (n=3) and 12 weeks (n=3). At sacrifice, the entire anterior chest wall was removed and dynamically fixed with formalin. Extensive histologic comparisons were performed on three tissue blocks taken from each ITA, 2, 8, and 24 cm from their origin. RESULTS: Flows at the end of the study were comparable to measurements taken during operation, immediately after skeletonization. Grossly, the ITA wall was not injured by skeletonization and there was no adventitial hematoma or bleeding from the sealed branch ends. Microscopic observations showed intact, normal wall structures. Histologic data showed no major significant difference between controls and skeletonized ITAs. CONCLUSIONS: Careful skeletonizing dissection is not detrimental to the integrity of ITAs, which justifies their use for myocardial revascularization.

Early flow surface endothelialization before microvessel ingrowth in accelerated graft healing, with BrdU identification of cellular proliferation.

The purpose of this report was to determine if flow surface endothelialization could precede microvessel ingrowth from the perigraft area in porous Dacron grafts, by using an accelerated graft healing model with short implant periods. Dacron grafts were implanted in the abdominal aorta of 22 dogs and wrapped in autogenous inferior vena cava (IVC), which provided excellent conditions for extramural angiogenesis, microvessel development, and ingrowth toward the graft. Retrieval times were 7 days (n = 4), 8 days (n = 5), 9 days (n = 4), 10 days (n = 3), 11 days (n = 4) and 12 days (n = 3) postoperatively. Graft surfaces were evaluated for thrombus coverage, cell coverage, and the number of micro-ostia. Components and cellular types in the graft wall and on the surface were studied and characterized with H&E, histochemical, and immunocytochemical staining. BrdU labeling was also used, to identify the areas where cells were actively proliferating. All grafts were patent. Although the degree of IVC/graft attachment varied, isolated islands of endothelial-like cells were found at the midgraft areas at each time period, and immunocytochemically confirmed as endothelial cells. There were two healing patterns: (1) surface endothelialization before microvessel/tissue ingrowth from the perigraft areas, and (2) surface endothelialization with full wall microvessel and tissue presence. Surface endothelialization was observed before perigraft tissue ingrowth, indicating that fallout healing is an independent source of endothelialization for porous grafts.

Apparent blood stream origin of endothelial and smooth muscle cells in the neointima of long, impervious carotid-femoral grafts in the dog.

The purpose of this study was to determine whether endothelial and smooth muscle cells originating from the blood stream contribute to the endothelialization of impervious, small-caliber, long Dacron grafts used as extraanatomical bypasses in dogs. We implanted silicone-rubber-coated, permanently impervious grafts 64 to 77 cm long and 6 mm in diameter, made of externally supported knitted Dacron as unilateral carotid-femoral bypasses with distal femoral arteriovenous fistulae in 10 dogs for 3 months; sides were alternated between cases. Subjects received 162 mg/day of aspirin, and its effectiveness on platelet aggregation (PA) was evaluated and expressed as a PA score. Graft healing was studied by stereomicroscopy with silver nitrate staining, by light microscopy with hematoxylin-eosin and immunocytochemical staining for endothelial and smooth muscle cells, and by scanning and transmission electron microscopy. Five grafts were patent for 3 months and could be included in the healing study; the five occluded grafts thrombosed within 14 days. Although there was no transinterstitial tissue ingrowth from perigraft tissues into the impervious Dacron grafts, scattered islands of endothelial cells were conclusively demonstrated on graft flow surfaces 3 months after implantation. Average endothelial-like cell coverage of the flow surfaces was 15.6% +/- 3.8%, and alpha-actin-positive smooth muscle cells and microvessels were found beneath some of the endothelial islands. These findings suggest that blood stream-derived endothelial and smooth muscle cells play a role in the healing of the inner wall of Dacron grafts in the dog.

Early presence of endothelial-like cells on the flow surface of porous arterial prostheses implanted in the descending thoracic aorta of the dog.

The purpose of this study was to investigate early arterial graft healing and its sources in porous Dacron prostheses after very short implantation periods in the dog, using extensive histologic examination of serial sections. Preclotted Dacron prostheses 6 cm long and 8 mm in diameter were implanted in the descending thoracic aorta (DTA) of 14 dogs, and retrieved at 7 days (n = 6), 10 days (n = 4), and 14 days (n = 4). The flow surface was assessed for thrombus coverage, endothelial-like cell (ELC) coverage, and the number of microvessel ostia. Where an ELC island was identified under the stereomicroscope, full-wall longitudinal tissue samples were taken, and embedded in resin for light microscopy study of 6-microns, H&E-stained serial sections to determine general healing and interstitial tissue presence. If there was more than one ELC island, another full-wall sample was taken and embedded in paraffin for staining with laminin, collagen IV, and smooth muscle alpha-actin antibodies, and PTAH. All grafts were patent with very little thrombus. Islands of endothelial-like cells were found for each time period, and on all 14-day grafts. Endothelial-like cell coverage was highest at 14 days. On 7- and 10-day grafts, cells proved to be endothelium were found in the middle of the flow surface, unconnected to either pannus or perigraft tissue ingrowth. Healing occurs as early as 7 days in porous knitted Dacron grafts. The source at periods earlier than 10 days appears to be cells from the blood stream.

Endothelium on the flow surface of human aortic Dacron vascular grafts.

PURPOSE: We have previously observed endothelium on two human vascular prostheses explanted under optimal conditions for flow surface preservation. In this study we sought to further verify the hypothesis that endothelialization can occur on clinical grafts and that it can be detected in specimens that have been promptly removed and properly preserved in a timely manner. METHODS: We studied 29 aortic grafts. Of these, 11 Dacron bypass grafts were in a condition suitable for analysis with light microscopy and immunocytochemistry staining, and scanning and transmission electron microscopy. RESULTS: Three grafts had endothelium beyond the pannus, identified by factor VIII/ vWF, Ulex europaeus agglutinin, and collagen IV positivity. Specimen A, a knitted 6-year implant, was preserved by embalming 3 hours after the patient's death and had a firmly attached outer capsule with fibroblasts, collagen, giant cells, and microvessels in the interstices. Specimen B, a woven 18-year implant, was retrieved at reoperation and immediately fixed in 10% formalin; it had no outer capsule and no tissue ingrowth. Specimen C, a woven 7-year implant, was removed and fixed 5 hours after the patient's death; it had a firmly attached outer capsule but no tissue ingrowth beyond the outer portion of the wall. CONCLUSIONS: The rapidity with which the specimens were fixed probably enabled identification of endothelium. These findings suggest that endothelialization of synthetic arterial grafts may occur more frequently in human beings than previously recognized.

Accelerated endothelialization model for the study of Dacron graft healing.

Accelerated endothelialization was studied by creating a vascular tissue environment around porous Dacron grafts. Three study groups, each containing 10 dogs, were divided equally into 2- and 4-week implant periods, with 8 mm x 6 cm knitted Dacron grafts implanted in the abdominal aorta. Grafts in group 1, the control group, were implanted conventionally. In group 2 each implanted graft was completely wrapped in a resected segment of the autogenous inferior vena cava, with its intima against the wall. In group 3 the adventitial side of the vein was wrapped against the wall. The vein wrap produced accelerated endothelialization as follows: endothelial-like cell coverage scores at 2 and 4 weeks were, respectively, 78% and 98% for group 2 and 80% and 95% for group 3, compared to only 14% and 50% for group 1 (p < 0.05). The neointima, which contained smooth muscle cells, was formed as early as 2 weeks in the vein-wrapped grafts. There were no differences in the speed of healing or in healing patterns according to whether the intimal or the adventitial side of the inferior vena cava was placed against the graft. Histologic findings did not support the hypothesis that accelerated flow surface endothelialization results in direct migration of endothelial cells from the intima of the vein wrap, and there was no clear correlation between the surface endothelial-like cell coverage and microostia. To gain further insight into why accelerated healing occurs in this model, earlier observations accompanied by molecular biology analysis are needed, and vein wrap studies provide a method of comparison for this work.

Implant site influence on arterial prosthesis healing: a comparative study with a triple implantation model in the same dog.

PURPOSE: The purpose of this study was to develop a cost-effective canine graft healing model that gives information on various implant sites and controls for variable factors between graft locations and between animals and to compare the influence of implant site (retropleural, retroperitoneal, and subcutaneous areas) on arterial graft healing in the same subject under such controlled study conditions. METHODS: Five mongrel dogs were studied for 8 weeks, and one was studied for 3 years. Each received three porous Dacron grafts during the same surgery: a carotid-femoral bypass (C-FB) and interposition grafts in the descending thoracic aorta and abdominal aorta. To produce comparable shear stress calibers of the C-FB and abdominal aorta grafts were 2 mm less than those of the descending thoracic aorta, and a distal arterio-venous fistula was created to further increase the C-FB flow. For comparable blood aggregation status platelet aggregation was preevaluated and adjusted with antiplatelet agents. Graft flow surfaces were assessed for thrombus-free surface and endothelial-like cell coverage scores. Tissue samples were studied with hematoxylin-eosin, factor VIII/ von Willebrand factor, smooth muscle alpha-actin staining, and scanning electron microscopy and transmission electron microscopy. RESULTS: All grafts were patent. Shear stress for the three grafts and platelet aggregation among the study subjects were comparable. Healing of descending thoracic aorta and abdominal aorta grafts was similar, but C-FB healing was slow, incomplete, and uneven, with a high incidence of seroma. Eight-week and 3-year results were comparable. CONCLUSIONS: This model gives broad healing information about the areas where grafts are often implanted in humans. Eight weeks appears to be a sufficient period to reflect basic and general healing characteristics. Grafts heal better in the retropleural and retroperitoneal areas than in the subcutaneous tissues.