Neuroma transposition and intramuscular implantation using the Mitek "soft-tissue anchor": a new technique.

The authors describe a new technique for intramuscular implantation of a nerve ending after peripheral neuroma excision. Sixteen peripheral neuromas in 10 patients were excised and then implanted into muscle tissue using the Mitek anchor. The positions of the anchors were documented by immediate anteroposterior and lateral radiographs. These views were repeated at 2 months to assess any migration. All patients had resolution of the symptoms related to their neuromas. No substantial migration was noted in any of the patients. The Mitek anchor can be used as a "soft-tissue" anchor to position a nerve ending reliably at a precise depth and tension in muscle tissue with minimal trauma.

Nerve growth factor inhibition prevents traumatic neuroma formation in the rat.

Nerve growth factor (NGF) is thought to play a role in the pathogenesis of neuroma formation as well as in the development of neuropathic pain. In this study we attempted to antagonize NGF by using trkA-IgG, an inhibitor of NGF, consisting of the NGF receptor linked to an immunoglobulin. It was delivered by an implanted osmotic pump directly to the site of a sciatic nerve transection in 16 rats for 30 days. The animals were monitored daily for the first 2 weeks for evidence of auto-cannibalization (autotomy) of the denervated foot (a sign of neuropathic pain). Four (25%) of the 16 rats receiving trkA-IgG exhibited such cannibalization compared with 9 of 15 control rats (60%) that underwent an identical procedure but were not treated with the trkA-IgG solution. One month after surgery the sciatic nerves and representative dorsal root ganglia (DRG) from these rats were evaluated histologically. Six of the 16 experimental rats (38%) demonstrated histological evidence of neuroma formation compared with 12 of the 15 controls (80%). There were no histological differences between the DRG from the two groups. These results support the notion that inhibiting NGF following peripheral nerve injury in the rat can reduce neuroma formation and neuropathic pain without damaging the cell bodies of the transected neurons.

Reconstruction of ureteral defects with microvascular vein grafts in a rat model.

This study was undertaken to test the performance of an autologous vein graft as a ureteral replacement in the rat model. Twenty-six rats were divided into three groups. In Group 1 (n = 10), the animals had a 3-mm segment of the ipsilateral ureter excised and the ureteral defect repaired, using a superficial epigastric vein graft. In Group 2 (n = 10), the same ureteral defect was created and again repaired, using a superficial epigastric vein graft, with the addition of a Silastic stent. The control, Group 3 (n = 6), had the ureter transected and repaired solely by means of primary anastomosis. Animals from each group underwent urography and were sacrificed for histology at three different postoperative intervals: 1, 4, and 12 weeks. Postoperative urography results showed normal renal function in the animals with ureteral reconstruction using vein grafting aided by a stent, as well as in those with primary ureteral anastomosis. No renal function return was seen in the animals with ureteral reconstruction by vein grafting alone, without stent support. Histologically, a progressive loss of the vascular endothelium, and replacement with the urothelium typical of the ureter, was seen in the stented vein grafts. Severe ureteral obstruction at the proximal site of the graft and hydronephrosis were seen in the vein-graft group without stenting. This study demonstrates that autologous vein grafts can be used successfully to correct a ureteral deficit, contingent on accurate microsurgical technique and immediate stenting.

Role of medical students in microsurgery research.

Microsurgery is an integral element in many surgical specialties, as well as an important technique for surgical research. Student participation in microsurgery research programs can be a source for both high quality training in skills and for research contributions. In this article, the authors review their experience in developing general principles for setting up medical student microsurgery research programs, and analyze the research output and career choices made by the students who have participated.

Improvement of skin paddle survival by application of vascular endothelial growth factor in a rat TRAM flap model.

The effect of vascular endothelial growth factor (VEGF) on skin flap survival and its ability to induce a pharmacological delay by promoting angiogenesis in a flap was studied in a rat transverse rectus abdominis musculocutaneous flap, using a 3 x 8-cm skin paddle with the inferior epigastric vessels as its main vascular supply. Forty-three Sprague-Dawley rats were divided into four groups. In group 1, VEGF was injected into the femoral vein after the flap was elevated. In group 2, VEGF was injected intra-arterially into the flap through the superior epigastric artery after the flap was elevated. In group 3, VEGF was injected into the subcutaneous fascial layer in the area where the flap would be dissected, and the flap was then raised 7 days after injection. In group 4, the flap was dissected and replaced, using saline injection as the control. On postoperative day 5, the survival area of each skin paddle was measured and the flap was harvested for histological analysis. The results showed that the mean survival area +/- standard deviation for the skin paddle was 6.82 +/- 4.89 cm2 (28.4 +/- 20.4% of the whole skin paddle) in the control group, and 4.2 +/- 3.0 cm2 (17.5 +/- 12.5%) and 6.02 +/- 5.97 cm2 (25.1 +/- 24.9%) in the groups with VEGF systemic and intra-arterial administration respectively. The skin survival area in the group with preoperative subcutaneous administration of VEGF was 17.85 +/- 2.88 cm2 (74.4 +/- 12%), which was significantly higher than the other three groups (p < 0.01). Histological semiquantitative analysis showed increased neovascularization in the flap treated with VEGF preoperatively. The data demonstrate that preoperative treatment with VEGF can induce angiogenesis and enhance skin paddle survival in a musculocutaneous flap.

A phase II trial of intraluminal irrigation with recombinant human tissue factor pathway inhibitor to prevent thrombosis in free flap surgery.

A multicenter, multinational, blinded, randomized, parallel-group, phase II study was conducted to investigate the use of recombinant human tissue factor pathway inhibitor (rhTFPI; SC-59735) as an antithrombotic additive to the intraluminal irrigating solution during microvascular anastomosis in free flap reconstructive surgery. A total of 622 patients undergoing free flap reconstruction were randomly assigned to three groups. For each group, a different intraluminal irrigating solution was administered at completion of the microvascular arterial and venous anastomoses and before blood flow to the flap was reestablished: rhTFPI at a concentration of 0.05 or 0.15 mg/ml (low-dose or high-dose group, respectively) or heparin at a concentration of 100 U/ml (current-standard-of-practice group). There were no other differences in treatment among the groups. Patient characteristics, risk factors, and surgical techniques used were similar among all three groups. Flap failure was lower (2 percent) in the low-dose rhTFPI group than in the high-dose rhTFPI (6 percent) and heparin (5 percent) groups, but this difference was not statistically significant (p = 0.069). There were no significant differences in the rate of intraoperative revisions of vessel anastomoses (11 percent, 12 percent, and 13 percent) or postoperative thrombosis (8 percent, 8 percent, and 7 percent) among the low-dose rhTFPI, high-dose rhTFPI, and heparin groups, respectively. The rate of postoperative wound hematoma was significantly lower in the low-dose rhTFPI group (3 percent) than in the high-dose rhTFPI (8 percent) and heparin (9 percent) groups (p = 0.040). There were no differences in blood chemistry or coagulation values among the three study groups. Other than hematomas, there were no differences in the incidence or severity of adverse reactions among the three groups. It is concluded that use of rhTFPI as an intraluminal irrigant during free flap reconstruction is safe, well tolerated, and as efficacious as use of heparin for preventing thrombotic complications during and after the operation. Furthermore, the lower dose of rhTFPI (0.05 mg/ml) may reduce the occurrence of postoperative hematoma and help prevent flap failure.

Microvascular transplantation of the rat submandibular gland.

Xerostomia results from salivary gland irradiation during treatment of head and neck malignancies. In addition to having difficulty with speech and swallowing, these patients experience loss of taste, dental caries, and chronic fungal infections. The paired submandibular glands provide 70 percent of the normal salivary flow and are difficult to shield during radiation therapy. Another sicca condition, xerophthalmia, may result from facial nerve injury or other medical disorders and results in pain, corneal ulceration, and possible vision loss. Treatment options for xerostomia are limited, and management of xerophthalmia usually focuses on the eyelids, rather than the fundamental problem of inadequate secretory protection. In this study, a rat model for submandibular gland microvascular transplantation was developed to assess the feasibility of salivary tissue transfer. Sixteen rats underwent submandibular gland transplantation from the neck to the groin. Fourteen of these rats underwent microvascular anastomosis of the vascular pedicle. Ten glands were assessed for viability at 4 days after transplantation, and four glands were examined after 7, 10, 14, or 21 days. By gross and histologic examination, 93 percent of transplanted glands showed expected long-term viability after at least 4 postoperative days. Microvascular techniques were shown to be applicable to the transplantation of submandibular gland salivary tissue. This has not previously been shown in a rat model. It is possible that submandibular glands could be transplanted to the eye for treatment of xerophthalmia and out of the neck during irradiation of the head and neck, with subsequent replantation after treatment as a means of preventing permanent xerostomia.

Free microvascular transfer of the acromiotrapezius osteomuscular flap in rats.

The acromiotrapezius-scapular spine osteomuscular flap is a new osteomuscular research model for use in microvascular free tissue transfer in rats. We performed anatomical studies to collect data on muscle weight, dimension, vessel calibre and bone size in 20 flaps. This flap has a triangular shape with an average size of 38 x 39 x 32 mm and an average weight of 1.25 g; the scapular spine of 20 mm in average length can be harvested with the flap. The pedicle can be taken in continuity with the cervical trunk (average diameter of artery and vein were 0.5 mm and 0.6mm, respectively, with an average pedicle length of 12 mm). The flap was harvested and transferred to the groin area of the same rat and anastomosed to the superficial epigastric vessels. Fifteen transplantations were performed and the 7-day flap survival was 93.3%. The acromiotrapezius flap is believed to be a new and reliable osteomuscular model in the rat.

Microvascular hand surgery-transplants and replants-over the past 25 years.

Two hundred eighty articles related to microvascular transplants and replants published in The Journal of Hand Surgery over the past 25 years were reviewed. Every facet of microsurgery was covered. One hundred seventy-one articles are referenced and discussed under the following major categories: microvascular transplants, replants, nerve grafts, vein grafts, cold intolerance, vasospasm, monitoring, immediate reconstruction, and historical. Contributions were received from 37 countries and 175 authors or groups of authors.

The effects of VEGF on survival of a random flap in the rat: examination of various routes of administration.

The purpose of the present study was to determine the effects of vascular endothelial growth factor (VEGF) on survival of a full thickness random pattern, McFarlane musculocutaneous flap in the rat. In addition, this study examined a number of different methods of VEGF delivery in an attempt to determine the most effective route of administration. A 2 x 8 cm full thickness dorsal flap with the pedicle remaining attached at the anterior end was elevated in 72 male Sprague-Dawley rats. The rats were randomised into six groups and immediately received the following treatment: Group I (n = 12): systemic VEGF injection into the femoral vein (50 microg/ml); Group II (n = 10): multiple systemic VEGF injections at 0, 24 and 48 h post flap elevation (50 microg/ml); Group III (n = 12): subdermal VEGF injection into the flap (1 microg/ml); Group IV (n = 12): subfascial VEGF injections into the recipient bed (1 microg/ml); Group V (n = 10): topical VEGF onto the recipient bed (1 microg/ml); Group VI (n = 16): control group with no treatment. Following 5 days recovery, the area of flap survival was measured. Mean flap survival ranged from 91% in Group II to 78% in Group V, and was significantly greater in all experimental groups (P< 0.001 for Groups I-IV and P< 0.05 for Group V) as compared to the control group (mean survival of 66%). The only significant difference between the experimental groups was between the mean survival in Group II and Group V (P< 0. 05). Histological analysis demonstrated a qualitatively greater amount of granulation tissue and neovascularisation in the experimental groups. These results support the notion that VEGF rescues tissue at risk of hypoxic damage by inducing angiogenesis, and the use of growth factors such as VEGF holds promise as a method of increasing skin viability.

Biliary tract reconstruction using an autologous vein graft in rats.

Numerous biologic and synthetic materials have been used with limited success as an interposed graft to repair segmental common bile duct (CBD) defects. The authors report here that an autologous vein graft can be successfully used to correct a CBD deficit contingent on accurate microsurgical technique immediate stenting and rapid graft vascularization. Thirty Sprague-Dawley rats underwent laparotomy and the experimental group (n=25) had a 3-mm segment of the CBD excised. The CBD defect was repaired using an interposed femoral vein graft aided by a plastic stent. The control group (n=5) had the CBD cut and repaired by means of primary anastomosis. The experimental group was subdivided into three sub-groups each examined at three different postoperative intervals: 1, 4 and 12 weeks. The results showed that inflammation was apparent in the venous wall following the first postoperative week. A progressive loss of the vascular endothelium and replacement with the columnar epithelium typical of the CBD was seen in the vein graft. Nineteen of the 25 experimental rats (76 percent) of the animals survived without complication from the surgery and there were no abnormalities in the liver biochemical tests of these animals. Any biliary tract obstruction that developed was attributed to dislocation of the stent leading to collapse of the vein graft (experimental group), or constriction of the anastomosis (control group). This study demonstrates that biliary tract reconstruction using an autologous vein graft can be successfully performed in a rat model of CBD repair. The application of this method to the clinical setting is also discussed.

Free vascularized fibular bone flap in the rat.

Free vascularized fibula bone flap has been widely used in reconstruction of the mandible, long segment defect, congenital pseudarthroses, and osteomyelitis. Such applications stirred an interest in basic studies of bone biology, bone healing process, and incorporation of recipient bone defect. An experimental free vascularized fibula rat model is presented here for such investigations. We performed 16 angiograms and anatomic dissections in eight rats for collecting data on fibular length, blood supply, and the caliber of significant vessels. The fibula was harvested with part of the flexor hallucis longus muscle with an average length of 28 mm. The pedicle can be taken in continuity with the popliteal vessels (average diameter of 0.8 mm and 0.9 mm of artery and vein, respectively, with an average pedicle length of 14 mm). This vascularized fibula bone was harvested and transferred to the groin area of the same rat and anastomosed to the saphenous vessels. Twelve transplantations were performed, with a 7-day flap survival rate of 100%. The free fibula vascularized bone flap in the rat is a reliable model for further investigations.

[Relation of venous drainage and inadequate circulation in the rat pedicled TRAM flap model].

OBJECTIVE: To evaluate the circulatory characteristics of the TRAM flap because the vascular supply to lateral portion of the conventional TRAM (zone 4) occasionally may become compromised resulting in necrosis of fat tissue or requiring segmental excision of the poor perfused tissue. METHODS: In this study, we designed a rat pedicled TRAM flap model with either inadequate arterial or venous circulation. The skin paddle was photographed and the survival areas were measured on the tenth postoperative day. RESULTS: The results showed that the group with poor arterial inflow of the flap, which resulted from ligation of the superior deep epigastric artery, exhibited skin necrosis in zone 1 and 2. Venous stasis due to selective ligation of the venous pedicle resulted in necroses of a major area in the lateral part of the flap, especially in zone 4. However, venous stasis may be alleviated by an additional cutaneous venous return system. CONCLUSIONS: Our results demonstrated that conventional rat TRAM flap with poor arterial inflow differs from that with venous stasis in terms of manifestations and extent of inadequate circulation. Necrosis of the lateral portion of human TRAM flaps may therefore be attributed to problems of venous stasis. Such problems might then be ameliorated by creating an additional cutaneous venous return system.

Effect of hyperbaric oxygen on microvascular anastomosis healing and patency in the rat.

Recent evidence has shown that changes in blood viscosity and marked increases in both platelet count and fibrinogen concentration occur after exposure to hyperbaric oxygen (HBO). The purpose of the present study was to address whether repeated HBO therapy would increase either hematocrit or platelet count, and to determine if these changes would influence the patency of the microvascular anastomosis, as well as anastomotic healing. Eighty femoral arteries from 40 rats were divided into four groups (n = 10), and arterial anastomoses were performed on normal arteries in the first two groups, and on crushed arteries in the second two groups. One of the normal artery groups and one of the crushed artery groups received repeated HBO treatments for 5 days. Anastomotic patency rates, platelet count, hematocrit, and breaking strength were recorded. Among the results of this study were that: (1) there was no difference in patency rate following HBO treatment in both the normal and crushed artery groups; (2) platelet count was significantly higher following HBO treatment in the groups with the undamaged arteries; (3) breaking strength was significantly increased following HBO treatment in the groups with the crushed arteries. The authors concluded that HBO therapy may be useful in improving the healing of microvascular anastomoses in vessels that have undergone crush injury. Although HBO treatment results in an increased platelet count, this does not influence anastomotic patency.

Saphenous neurocutaneous island flap model in the rat: evaluation of vascular supply.

Neurocutaneous flaps are utilized routinely in reconstructive surgery and even more so during the past decade. In this study, the vascular supply of the neurocutaneous flap in the rat model is presented and evaluated. Thirty-six flaps (3.5x3 cm2) were dissected on the medial aspect of the leg based on a pedicle of the saphenous nerve, saphenous artery, great saphenous vein, and the surrounding fascial tissues. Animals in the experiment were divided into five groups with different circulatory patterns of pedicle dissections. In group I (N = 12), the pedicle artery, vein, nerve, and fascia were preserved. In group II (neurocutaneous flap model, N = 24), the saphenous artery was transected and the vein, nerve, and fascia were preserved. In group III (intraneural vascular plexus circulation pattern, N = 12), the saphenous artery and the fascia were transected. In group IV (extraneural vascular plexus circulation pattern, N = 12), the saphenous artery and nerve were transected. In group V (N = 12), the entire pedicle was transected completely. Flap survival was evaluated grossly on postoperative day 7. All flaps survived in group I, but in group II 19 of 24 flaps survived completely, 3 of 24 had partial necrosis, and 2 of 24 were completely necrotic. Complete necrosis was observed in all group III flaps. In group IV, 6 of 12 flaps survived completely, 3 of 12 flaps survived partially, and 3 of 12 flaps were necrotic (p<0.05 vs. group I). Only one flap with partial necrosis survived in group V. In group II, the average survival area was not significantly different from group I (p>0.05). In conclusion, the saphenous neurocutaneous flap in the rat is a reliable microsurgical model. The saphenous neurocutaneous flap is commonly supplied by both the intraneural and extraneural vascular plexus, and although the latter is more important, neither provides sufficient vascular supply on its own.

Prolonged perivascular use of verapamil or lidocaine decreases skin flap necrosis.

During this experiment the authors investigated whether prolonged local use of verapamil or lidocaine prevents vasoconstriction and establishes better blood supply to the rat epigastric skin flap, hence reducing the necrosis that occurs otherwise. Abdominal wall skin flaps of 45 Sprague-Dawley rats, based on a single pedicle of the femoral vessels, were elevated. A subcutaneous pocket for the microport valve was created, and the adjacent catheter tip was sewn next to the femoral vessels. In the control and the two treatment groups, 0.5 ml saline or vasodilator solution respectively was injected through the microport every 12 hours for 5 days. On postoperative day 5 there was no statistical difference between the flap surfaces in all groups. The area of flap necrosis was significantly lower in the verapamil- (p = 0.001) and the lidocaine-treated (p = 0.012) groups vs. the control group as determined by analysis of variance with Bonferroni's post hoc test. In conclusion, topical application of verapamil and lidocaine solutions for 5 postoperative days decreased flap marginal necrosis significantly. Prolonged injection of vasodilators in the vicinity of the vascular pedicle prevents vasospasm and improves blood supply to the flap.

Quadriceps femoris muscle flap: largest muscle flap model in the rat.

The purpose of this paper is to present a new muscle flap in the rat: the quadriceps femoris muscle flap based on a pedicle consisting of the femoral vessels. In order to establish the anatomic details of this model, seven rats were explored bilaterally, and the regional anatomy of the thigh was examined. The technical aspect of the model was established by the unilateral harvesting of 18 quadriceps femoris muscles. Findings were that this muscle is primarily supplied by a muscular branch originating at the superficial circumflex iliac artery. The average muscle weight was 6 g and the average pedicle length with femoral vessels was 6 mm. Eight of the harvested flaps were transplanted to the contralateral thigh, and the pedicle was anastomosed to the femoral vessels. The other ten flaps were resutured back to their beds. At 72 hr postoperatively, all flaps were viable with the exception of one of the transplanted flaps which was found to be necrotic. The quadriceps femoris muscle flap is technically both a reliable and simple model. With an average weight of 6 g, this flap is by far the largest described in the rat, and offers a convenient model for testing flap-related techniques and outcomes.

Patterns of flap loss related to arterial and venous insufficiency in the rat pedicled TRAM flap.

Vascular supply to the contralateral portion of the conventional transverse rectus abdominis musculocutaneous (TRAM) flap (zone IV) may become compromised, resulting in partial flap loss and requiring segmental excision. The etiology of this necrosis is not clear. This study determines skin necrosis patterns on a superiorly pedicled caudal TRAM flap during conditions of venous and arterial insufficiency, and determines whether cutaneous venous outflow can sustain a flap with venous insufficiency. Twenty-eight adult male Sprague-Dawley rats underwent superior pedicled TRAM flap elevation, and the zones were marked on the skin paddle. The animals were divided into four groups: control (group A, N = 6), arterial ligation (group B, N = 6), venous ligation (group C, N = 8), and venous ligation with cutaneous venous outflow (group D, N = 8). After 10 days, the skin paddle was photographed and the areas of necrotic skin were measured. Results showed that group B (selective arterial ligation) had 51.7 +/- 2.8% and 40.0 +/- 2.0% skin necrosis in zones I and II respectively. Zone I necrosis was significantly greater in group B compared with the control (p < 0.05). Group C (selective venous ligation) resulted in 73.8 +/- 16.4% and 93.8 +/- 33.4% skin necrosis in zones III and IV respectively. This necrosis was significantly greater compared with the control (p < 0.001). Group D rats' lateral skin necrosis compared significantly less with group C (p < 0.001). These results demonstrate that the patterns of flap necrosis in rat TRAM flaps with poor arterial inflow differ from those with venous stasis. Necrosis of the contralateral portion (zone IV) of human TRAM flaps may be related to problems with venous stasis; thus, a cutaneous venous outflow may prevent this problem.

Effects of VEGF administration following ischemia on survival of the gracilis muscle flap in the rat.

The incidence of free flap transplantation failure is only 3% to 5%, yet still occurs in cases in which the flap suffers prolonged ischemia. The purpose of the current study was to determine the effects of vascular endothelial growth factor (VEGF)--a potent angiogenic agent with a suspected role in the protection of endothelium--on flap survival in a model of ischemia-reperfusion injury. The model chosen was the rat gracilis muscle flap. A total of 36 adult male Sprague-Dawley rats were divided into three groups (N = 12). One experimental group received VEGF treatment and the other received heparin. A third group was treated with saline and served as the control. The gracilis muscle flap was dissected and isolated based on a vascular pedicle originating at the femoral vessels. Following 3.75 hours of ischemia, induced by clamping the femoral vessels, either VEGF, heparin, or saline was infused directly into the pedicle of the flap via a cannula. The flaps were evaluated both grossly and histologically after 72 hours of reperfusion. Eleven of the 12 flaps from the VEGF group survived, whereas the survival rate was 6 of 12 and 5 of 12 flaps for the heparin- and saline-treated groups respectively. Flap survival was significantly greater in the VEGF-treated group compared with the heparin- and saline-treated groups (p < 0.025, p < 0.01 respectively). Furthermore, there was no significant difference between the heparin and saline groups. These results indicate that VEGF plays a role in reducing the damage that occurs in ischemia-reperfusion injury, and that the use of VEGF holds promise as a potential therapy for increasing flap survival.