Intramuscular Grafts Research Articles

Assessment of primary patency for femoropopliteal graft entrapment within the sartorius muscle

PurposeBlind tunneling of subfascial femoropopliteal bypass grafts may result in inadvertent graft passage through the sartorius. The purpose of this study was to determine whether intramuscular passage of femoropopliteal bypass grafts affects primary patency.MethodsPatients undergoing femoropopliteal bypass at a Veterans Administration hospital and associated university medical center over a recent 13-year period who also had postoperative cross-sectional imaging adequate to determine graft location were examined. Five-year primary patency of grafts circumferentially enveloped by the muscle was compared with that of both extramuscular subfascial grafts and subcutaneous grafts.Results370 femoropopliteal grafts were identified, among which 258 (70%) were subfascial. Vein grafts comprised 51% of the subfascial grafts, and 53% were inserted above the knee. Available postoperative imaging in 110 subfascial grafts demonstrated 74 (67%) to lie completely within the muscle at some point. Among imaged subfascial grafts, primary patency at five years for intramuscular grafts was not significantly worse than extramuscular grafts (P = 0.31). This remained true whether grafts were vein (P = 0.39) or prosthetic (P = 0.31) and whether grafts inserted to the above-knee (P = 0.43) or below-knee (P = 0.21) popliteal artery. Multivariable Cox regression revealed a significant relationship between use of vein grafts (P = 0.013), active smoking (P = 0.01), and hypertension (P = 0.041) and primary patency, but not intramuscular graft location (P = 0.31).ConclusionThis study failed to demonstrate significantly inferior primary patency among subfascial femoropopliteal grafts tunneled intramuscularly. Larger studies may be required to adequately detect any differences in patency by muscular entrapment, especially among subgroups.

Engraftment and reversal of diabetes after intramuscular transplantation of neonatal porcine islet-like clusters.

Intraportal infusion is currently the method of choice for clinical islet cell transplantation but suffers from poor efficacy. As the liver may not represent an optimal transplantation site for Langerhans islets, we examined the potential of neonatal porcine islet-like clusters (NPICCs) to engraft in skeletal muscle as an alternative transplantation site. Neonatal porcine islet-like clusters were isolated from 2- to 5-day-old piglets and either transplanted under the kidney capsule (s.k.) or injected into the lower hindlimb muscle (i.m.) of streptozotocin-diabetic NOD-SCID IL2rγ(-/-) (NSG) mice. Survival, vascularization, maturation, and functional activity were analyzed by intraperitoneal glucose tolerance testing and immunohistochemical analyses. Intramuscular transplantation of NPICCs resulted in development of normoglycemia and restored glucose homeostasis. Time to reversal of diabetes and glucose tolerance (AUC glucose and AUC insulin) did not significantly differ as compared to s.k. transplantation. Intramuscular grafts exhibited rapid neovascularization and graft composition with cytokeratin-positive ductal cells and beta cells at post-transplant weeks 2 and 8 and after establishment of normoglycemia was comparable in both groups. Intramuscular injection represents a minimally invasive but efficient alternative for transplantation of NPICCs and, thus, offers an attractive alternative site for xenotransplantation approaches. These findings may have important implications for improving the outcome and the monitoring of pig islet xenotransplantation.

Fat embolism in liposuction and intramuscular grafts in rabbits

To evaluate the effects of fat embolism in organs such as lung and liver. Twenty rabbits underwent autologous intramuscular fat grafting in the right thigh after liposuction. The groups were determined according to the postoperative day that occurred in euthanasia: 60, 90 and 120 day. Then, lung and liver were excised and sent to the histopathology laboratory for analysis in search of late injury secondary to a prior event of fat embolism in the tissues. The results showed a change in the macroscopic sample with discoloration of the liver tissue heterogeneously. There were no changes consistent with embolic effect under the microscope. The option of performing a technique of fat grafting with a less traumatic surgical procedure can be considered protective against embolic events, with no impact to late embolic events on the tissues.

Xenotransplantation of human ovarian tissue to nude mice: comparison between four grafting sites

This study was designed to assess the impact of different ovarian tissue transplantation sites on the follicular pool and ovarian tissue integrity after short-term grafting, since there is no consensus in the literature as to the optimal grafting site in experimental models. Frozen-thawed ovarian tissue from eight patients was grafted for 1 or 3 weeks to the peritoneum, inside the ovarian bursa, under the skin and into the muscle of 16 nude mice. Assessment of follicular density and follicle classification was carried out by histological analysis. Proliferative activity was evidenced by immunostaining with anti-Ki-67 antibodies, and fibrotic areas were analyzed by morphometry on histological slides. One week post-transplantation, the proportion of Ki-67-positive primordial follicles was higher (20-42%) than in controls (1.7%), demonstrating follicular activation in all four sites. Despite this activation, primordial follicles were still found 3 weeks post-grafting, (34.1-66.9% of the follicle population), most of them quiescent, as indicated by the absence of Ki-67 immunostaining. Cryopreservation and grafting resulted in extensive fibrosis in the stroma. This fibrosis was significantly less pronounced in intramuscular (IM) grafts, representing 18.8% of the surface versus 44.7-60.5% for other sites, after 3 weeks of grafting. All four grafting sites equally supported early follicular growth and preserved some quiescent follicles after short-term frozen-thawed human ovarian tissue transplantation. The extensive fibrosis observed does not appear to have a major impact on early follicle development, but its long-term effects must be investigated. The graft environment may be implicated in the preservation of the stroma, as suggested by a lower degree of fibrosis in the IM site.

Intramuscular grafts of myoblasts genetically modified to secrete glial cell line-derived neurotrophic factor prevent motoneuron loss and disease progression in a mouse model of familial amyotrophic lateral sclerosis.

Effects of ex vivo GDNF gene delivery on the degeneration of motoneurons were studied in the G1H transgenic mouse model of familial ALS carrying a human superoxide dismutase (SOD1) with a Gly93Ala mutation (Gurney et al., 1994). Retroviral vectors were made to produce human GDNF or E. coli beta-galactosidase (beta-Gal) by transient transfection of the Phoenix cell line and used to infect primary mouse myoblasts. In 6-week-old G1H mice, 50,000 myoblasts per muscle were injected bilaterally into two hindlimb muscles. Untreated G1H and wild-type mice served as additional controls. At 17 weeks of age, 1 week before sacrifice, these muscles were injected with fluorogold (FG) to retrogradely label spinal motoneurons that maintained axonal projections to the muscles. There were significantly more large FG-labeled alpha motoneurons at 18 weeks in GDNF-treated G1H mice than in untreated and beta-Gal-treated G1H mice. A morphometric study of motoneuron size distribution showed that GDNF shifted the size distribution of motoneurons toward larger cells compared with control G1H mice, although the average size and number of large motoneurons in GDNF-treated mice were less than that in wild-type mice. GDNF also prolonged the onset of disease, delayed the deterioration of performance in tests of motor behavior, and slowed muscle atrophy. Quantitative, real-time RT-PCR and PCR showed persistence of transgene mRNA and DNA in muscle for up to 12 weeks postgrafting. These observations demonstrate that ex vivo GDNF gene therapy in a mouse model of FALS promotes the survival of functional motoneurons, suggesting that a similar approach might delay the progression of neurodegeneration in ALS.

Revascularisation of bone grafts in rats.

Revascularisation of syngeneic and allogeneic intramuscular bone grafts have been studied using radioactive microspheres to measure the ingrowth of blood vessels. New bone formation and resorption were measured by 85strontium uptake and by graft weight reduction. Revascularisation, and mineralisation rate were significantly higher in syngeneic grafts than in allogeneic grafts at two, three and six weeks after implantation. The syngeneic grafts lost weight faster indicating that the allogeneic grafts resorbed more slowly. The ingrowth of new vessels is impaired in allogeneic bone, and this probably inhibits the rate of bone formation and resorption of the grafts.

Carcinoembryonic antigen and glucose phosphate isomerase in a human colonic cancer model (GW-39)

Levels of carcinoembryonic antigen (CEA) and glucose phosphate isomerase (GPI) have been compared in the circulating blood of hamsters bearing intra-muscular grafts of GW-39 human colonic tumour. CEA in the sera of GW-39 tumour-bearing hamsters ranged from 2-6 to 8-4 ng/ml (mean = 4-5 +/- 1-7 ng/ml). GPI in the sera of normal hamsters ranged from 332 to 749 iu/1 (mean = 602 +/- 110 iu/1) while those with 14-week-old intra-muscular grafts of a hamster amelanotic melanoma, (A.Mel.3), or GW-39 human colonic carcinoma had a range of 664 to 1267 iu/1 (mean = 1024 +/- 220 iu/1) and 1430 to 4719 iu/1 (mean = 2065 +/- 601 iu/1) respectively. Thus, the ratio of enzyme activity in GW-39, A.Mel.3, and normal hamsters was 3-4:1-7:1, indicating a significant elevation (P less than 0-01) in animals bearing a human colon carcinoma or a hamster melanoma, with particularly high values obtained in hamsters with GW-39. Sequential determinations of CEA and GPI in a group of hamsters transplanted intra-muscularly with GW-39 tumours revealed that both markers increased proportionately with duration of tumour growth, suggesting that both serum CEA and GPI may be used as measures of tumour growth. The concentration of GPI in GW-39 human colonic carcinoma xenografts was also significantly higher than that measured in normal human colon, primary human colonic cancer, or normal hamster tissues. These results support the view that GPI, in addition to CEA, is a quantitatively increased marker in this tumour model, and is liberated into the circulation in proportion to the increase in tumour mass.

Effect of median eminence lesions on the function of multiple pituitary homografts with particular reference to the secretion of gonadotrophins and growth hormone.

Multiple intramuscular pituitary grafts in hypophysectomized, weanling rats stimulated growth and testicular development to levels intermediate between those of hypophysectomized and intact animals. Bilateral median eminence lesions produced 40 days after grafting inhibited growth as indicated by changes in nose-tail length and reduced testicular weight. When unilateral castration was performed at the time of placement of hypothalamic lesions, testicular weight also declined and the decline was related to the size of the removed testis. Unilateral castration of grafted control rats, on the other hand, was followed by an enlargement of the second testis. Weights of sex accessories also declined after lesions in the median eminence in comparison with grafted controls. It therefore appears that the residual function of ectopic pituitary tissue is at least in part under hypothalamic influence which is presumably mediated by circulating gonadotrophin-releasing factors. (Endocrinology 84: 595, 1969)

CONDITIONS DETERMINING THE TRANSPLANTABILITY OF TISSUES IN THE BRAIN

In confirmation of Shirai's observation, we find that transplantable mouse tumors grow actively when inoculated into the brains of rats, guinea pigs, and pigeons, whereas subcutaneous or intramuscular grafts in the same animals fail. This growth of foreign tissue in the brain, however, takes place only when the grafted material lies entirely in the brain tissue; if it comes in contact with the ventricle a cellular reaction takes place with resultant destruction of the graft. The growth of foreign tissue in the brain may be completely inhibited by simultaneous inoculations of a small bit of autologous but not by a bit of homologous spleen tissue. Mice highly immune to subcutaneous transplants of mouse cancer show no resistance to such tumors when the inoculation is made into the brain. Although the brain is without obvious power of resistance to implants of transplantable heteroplastic mouse tumors, yet grafts of spontaneous tumors fail to grow there even, as a rule, when tumor implanted and animal host are of the same species.