Genetically modified fibroblasts induce angiogenesis in the 3×6 cm rat epigastric island flap

The hypothesis as to whether gene therapy may induce functional angiogenesis in the rat superficial epigastric island flap would allow earlier pedicle division, was tested and the results are presented. Autologous rat fibroblasts were grown, harvested, cultured and retrovirally transfected to produce platelet-derived growth factor (PDGF)-AA, an angiogenetically active protein. Stable gene expression was monitored by PDGF-AA enzyme-linked immunosorbent assay (ELISA). One hundred eighty animals were divided into three groups (I-III) and a bilateral flap created in each animal. In all experiments, the right-sided flap was subjected to the experimental treatment and the left-sided flap served as control (1 ml saline 0.9%). During flap elevation, group 1 received 5×10⁶ genetically modified fibroblasts (GMFB ) plus 1 ml DMEM as medium. Group 2 was treated with 5×10⁶ non-modified fibroblasts (NMFB ) plus 1 ml medium; and group 3 received 1 ml medium alone. The flaps were sutured back and the vascular pedicle was bilaterally ligated and divided in each batch of 10 animals during the following 6 days. Seven days later, the flaps were harvested, the amount of necrosis measured and histologically examined. The GMFB produced up to 560 times more PDGF-AA than the NMFB, measured by ELISA. Clinically, the GMFB-treated flaps tolerated surgical division of the vascular pedicle significantly earlier than groups 2 and 3. Histologically, fibroblasts persisted in all flaps of groups 1 and 2 without major inflammatory reaction. In all GMFB-treated massive angiogenesis could be demonstrated. By means of retroviral gene transfer autologous rat fibroblasts can be genetically modified for stable expression of the PDGF-A gene to produce high amounts of PDGF-AA, which is angiogenetically active. After injection into the panniculus carnosus, these cells induce functional angiogenesis to permit earlier division of the vascular pedicle in this flap model.     

Platelet-derived growth factor-AA-mediated functional angiogenesis in the rat epigastric island flap after genetic modification of fibroblasts is ischemia dependent

BACKGROUND: The aim of this study was to induce therapeutic angiogenesis in ischemically challenged flap tissue by means of gene transfer. METHODS: Isogenic rat fibroblasts were retrovirally transfected to produce platelet-derived growth factor (PDGF)-AA. Stable gene expression was monitored by PDGF-AA enzyme-linked immunosorbent assay. Eighty animals were divided into 2 groups (1 and 2), each with 4 subgroups. The angiogenic target was a 7 x 7-cm epigastric island flap used as a necrosis model. Group 1 received flap treatment 1 week before flap elevation: 10(7) genetically modified fibroblasts, expressing PDGF-AA (genetically modified fibroblasts) plus 1 mL of Dulbecco's modified Eagle's medium (DMEM) (1A), 10(7) nonmodified fibroblasts (NMFB) plus 1 mL of DMEM (1B), 1 mL of DMEM (1C), and 1 mL of sodium chloride 0.9% (1D). All substances were injected at evenly distributed spots into the panniculus carnosus of the entire flap. Group 2 had the same flap treatment at the day of flap elevation. All flaps were sutured back. Seven days later, the flaps were harvested and examined both clinically, histologically, and immunohistochemically. RESULTS: In vitro, the GMFB produced up to 117.9 +/- 57.2 ng of PDGF-AA/mL medium during a 4-day period, compared with 0.7 +/- 0.6 ng of PDGF-AA/mL medium produced by NMFB in the same time period. In vivo production of PDGF-AA in flaps amounted to 1.3 +/- 0.7 ng of PDGF-AA/1 microL flap tissue for group 1A and 1.7 +/- 1.1 ng of PDGF-AA/1 microL flap tissue for group 2A seven days after cell transplantation. Fibroblasts persisted in all flaps from groups 1A, 1B, 2A, and 2B without major inflammatory reaction. Clinically, group 2A developed significantly less flap necrosis compared with all other groups, including group 1A. Accordingly, only group 2A gave significant histologic and immunohistochemical evidence for enhanced angiogenesis within the flap tissue. CONCLUSIONS: After retroviral gene transfer, isogenic rat fibroblasts produce high amounts of PDGF-AA in vitro. In vivo, PDGF-AA can be detected in flaps receiving genetically modified fibroblasts, which suggests survival of the implanted fibroblasts in this model. PDGF-AA produced by GMFB can induce flap angiogenesis only under ischemic conditions in this model. Transplantation of PDGF-AA-overexpressing fibroblasts results in higher flap survival in this model.     

Accelerating flap maturation by vascular endothelium growth factorin a rat tube flap model.

The effect of exogenous vascular endothelium growth factor (VEGF) on the survival of the distal skin paddle with early pedicle division was studied in a rat tubed pedicle flap model. In part I, tubed pedicle skin flaps were created on the backs of 14 rats. The pedicle was divided after an interval of 3, 4, 5 or 7 days, and the survival area of each distal skin paddle was measured 5 days after the pedicle was divided. The percentages of survival were 0, 24.9%, 89.9% and 100%, respectively. In part II, tube flaps were created in 20 rats. In the experimental group, 2 ml of VEGF (50 microg ml(-1)) was injected into the recipient bed during tube flap creation in each rat. In the control group, 2 ml of saline was given. The tubed pedicle was divided 4 days after creation. The mean survival area of the distal skin paddle in the group treated with VEGF was 7.32 +/- 1.36 cm(2) (80.91%) at 5 days after pedicle division, which was of statistical significance when compared with the survival in the control group of 2.70 +/- 1.89 cm(2) (27.9%). The histology showed angiogenesis at the skin paddle-recipient bed interface following VEGF injection. These results demonstrate that the subcutaneous administration of VEGF into the recipient bed of the tube flap transfer can induce angiogenes is at the junction between the donor and the recipient bed, and improve skin paddle survival with early pedicle division.     

Effect of clamp versus anastomotic-induced ischemia on critical ischemic time and survival of rat epigastric fasciocutaneous flap

BACKGROUND: There are many models used to explore ischemic-related phenomena. The rat epigastric fasciocutaneous flap model is the one most commonly used. Critical ischemic time is the maximum ischemic insult that tissue can undergo and still remain viable. Experimentally, ischemia is induced either by clamping the vascular pedicle or by dividing the pedicle then performing microvascular arterial and venous anastomosis. We sought to determine what effect the different methods of inducing ischemia have on the critical primary ischemic time and, thus, flap survival. METHODS: A right 3 cm x 6 cm groin flap based on the inferior epigastric vessels was raised in each rat. Ischemic times of 4, 6, 8, or 10 hours were induced either by placing temporary occlusion clamps on each vessel of the vascular pedicle (island pedicle group) or by ligation and division of the pedicle with subsequent microvascular anastomosis (free flap group). Survival was assessed at 7 days. RESULTS: The primary ischemic time at which one half of free flaps are predicted to die was calculated to be 7.60 hours, compared with 6.09 hours for the island pedicle flaps (p<.05). CONCLUSIONS: Fasciocutaneous flaps undergoing ligation and anastomosis are more resistant to ischemia than are those undergoing clamping of the pedicle. Possible etiologic factors responsible for this experimental finding are discussed.     

The influence of postoperative vessel occlusion on the viability of free microvascular skin-fat flaps and island flaps in rats

Using a method of vascular pedicle ligation without skin incision, some minor differences were found between the progress of neovascularization in microvascular free skin-fat flaps and island flaps, both with and without 1-hr ischemia in rats. Viable flap areas were established following vascular pedicle ligation (both vessels or only artery or vein), on the third day after flap replantation in both island and free flaps. Vascular pedicle occlusion on the fifth day after operation resulted in complete survival of free flaps only. Island flaps survived completely following vascular pedicle ligation on the seventh postoperative day. A clear correlation existed between the timing of vascular pedicle ligation and the necrosis and shrinkage rates. In free flaps, clinical signs of viability disturbances were seen earlier in single or total vascular pedicle occlusions, on the third or fourth day compared with island flaps. Insufficiency of the pedicle vein in island or free flaps was tolerated earlier than arterial or total pedicle occlusion. Venous occlusion three days after flap replantation caused significantly higher necrosis and shrinkage rates (p less than 0.05) in free flaps than in island flaps.     

Use of fascial grafts as an interface in flap prefabrication: an experimental study.

An experimental study was conducted to investigate whether a fascial graft can be used as an interface between a vascular pedicle and target tissue to augment tissue survival in a prefabricated flap. Thirty-six male Sprague-Dawley rats were divided into three experimental groups according to the type of the recipient bed prepared for the vascular implantation. The left saphenous vascular pedicle was used as the vascular source. A 9 x 9-cm inferiorly based peninsular abdominal flap was elevated in each animal. In group I, the pedicle was tacked beneath the abdominal flap, in which the epigastric fascial layer was untouched. In group II, a 3 x 5-cm graft of epigastric fascia was harvested from the abdominal flaps under loupe magnification. The graft was sutured back into its original position after a 180-deg rotation. The vascular pedicle was then implanted just beneath the center of the fascial graft. In group III, the same size of epigastric fascia was removed in the same manner as group II, exposing the subcutaneous layer for pedicle implantation. Four weeks later, abdominal flaps were raised as island flaps connected only to the saphenous pedicle and were sutured in place. Flap viability was assessed visually on day 7. Overall, the ultimate flap survival in group I was the largest, with some necrotic areas at the periphery of the flaps. In group II, flap survival was typically centralized over the fascial graft, and crescent-shaped necrosis was noted superiorly. In group III, an almost linear pattern of survival overlying the vascular pedicle was observed. The mean surviving flap area of group I (12.13 +/- 1.615 cm2) was statistically greater than that of group II (8.83 +/- 0.663 cm2, p < 0.001) and group III (6.3 +/- 0.815 cm2; p < 0.001). There was a statistically significant difference between the mean flap survival in groups II and III (p < 0.001). Vascular arborization was examined by microangiography, and specimens were processed for histological staining. In group II, vascularization was distributed in a larger area along the fascial graft in comparison with limited vascularization around the pedicle in group III. In this study it was revealed that the interposition of a fascial graft as an interface between the vascular source and the target tissue seems to increase the size of the prefabricated flap.     

Clinical experience with the lateral septocutaneous superior gluteal artery perforator flap for autologous breast reconstruction

Background: Superior gluteal artery perforator (SGAP) flaps are a useful adjunct for autologous microvascular breast reconstruction. However, limitations of short pedicle length, complex anatomy, and donor site deformity make it an unpopular choice. Our goals were to define the anatomic characteristics of SGAPs in cadavers, and report preliminary clinical and radiographic results of using the lateral septocutaneous perforating branches of the superior gluteal artery (LSGAP) as the basis for a modified gluteal flap. Methods: We performed 12 cadaveric dissections and retrospectively reviewed 12 consecutive breast reconstruction patients with gluteal flaps (19 flaps: 9 LSGAP, 10 traditional SGAP) over a 12‐month period. The LSGAP flap was converted to traditional SGAP in 53% of flaps because of dominance of a traditional intramuscular perforator. Preoperative 3D computed tomography angiography (CTA) and cadaveric dissections were used to define anatomy. Anatomic, demographic, radiographic, perioperative, and outcomes data were analyzed. Mean follow‐up was 4 ± 3.4 months (range 4 weeks to 10 months). Results: Compared with the pedicle in the SGAP flap, the mean pedicle length in the LSGAP flap was 1.54 times longer by CTA, 2.05 times longer by cadaver dissection, and 2.36 times longer by intraoperative bilateral measurement. These differences were statistically significant (P < 0.001). Clinically, 100% of the flaps survived. Conclusions: LSGAP flap reconstruction is advantageous, when feasible, because of the septocutaneous pedicle dissection and gain in pedicle length that make microsurgical anastomoses easier without compromising gluteus function. © 2010 Wiley‐Liss, Inc. Microsurgery 30:339–347, 2010.     

The effect of twisting on single and double based perforator flap viability: An experimental study in rats

In this study, the histological and vital effects of rotation on multiple and single based perforator flaps were evaluated. A 6 cm × 6 cm abdominal perforator flap model was used on 80 male rats; half of these received a single‐pedicled flap, and the other half double‐pedicled. The flaps of control subgroups were raised and sutured without rotation. In rotation subgroups 90‐, 180‐, 270‐degree rotations were performed, and rotation effects on flap viability and histological changes were analyzed. Among single‐ and double‐pedicled perforator flaps, respectively, mean survival area was 12.59 cm² and 27.84 cm² in non‐rotated subgroups, 12.49 cm² and 17.06 cm² in 90‐degree rotation subgroups, 5.96 cm² and 9.96 cm² in 180‐degree rotation subgroups, and 1.45 cm² and 1.70 cm² in 270‐degree rotation subgroups. While survival areas of double‐ and single‐pedicled perforator flaps with the same rotation degree showed no statistically significant difference, non‐rotated double‐pedicled perforator flaps had a statistically larger survival area compared to single‐pedicled perforator flap (P = 0.001). In the single‐pedicled flap group, there were no statistical differences between survival flap areas of the non‐rotated subgroup and the 90‐ and 180‐degree rotation subgroups (P > 0.05), but the non‐rotated subgroup had a statistically larger survival area compared to the 270‐degree rotation subgroup (P = 0.003). In double‐pedicled perforator flap group, the control subgroup had a statistically larger flap survival area compared to 90‐degree, 180‐degree, and 270‐degree rotation subgroups (P = 0.004, P = 0.002, P = 0.001). Degenerative histological changes gradually increased in correlation with the rotation angle in both single‐ and double‐pedicled groups. When double‐ and single‐pedicled groups were compared; degenerative histology score displayed no statistical difference between control subgroups and rotated subgroups (P > 0.05). In this rat abdominal propeller perforator flap model, we found that double perforators without pedicle rotation could support larger flap survival when compared to the single pedicle. However, double perforators did not cause an increase of survival area when pedicles were rotated. In the single‐pedicled perforator flap, the flap survival area did not significantly decrease until 180‐degree pedicle rotation. In the double‐pedicled perforator flap, the flap survival area decreased when the degree of rotation increased. The degenerative changes increased in correlation with the rotation degree in both single‐ and double‐pedicled perforator flaps. © 2014 Wiley Periodicals, Inc. Microsurgery 34:464–469, 2014.     

Rat strain differences in flap tolerance to ischemia

The rat epigastric island flap model is commonly used to explore ischemia-related phenomena. We sought to evaluate strain differences in tolerance to ischemia using two commonly used rat strains: Sprague-Dawley and Lewis. Epigastric flaps (3 × 6 cm) based on the superficial epigastric artery and vein were raised bilaterally in each rat (2 flaps/rat). Ischemia was induced for 10, 12, 14, or 16 hours by placing temporary occlusion clamps on each vessel of the vascular pedicle. Surviving flap areas were assessed planimetrically after 7 days. The average area of surviving flap tissue was greater in the Lewis rats for all ischemia times; this achieved significance for 12 hours and 14 hours of ischemia (P<0.005). These findings indicate that comparisons among studies on rat flap ischemia must take into account the particular strain used. Furthermore, these findings suggest an inherent capacity of Lewis rat tissue to withstand ischemia better than tissue of the Sprague-Dawley rat strain. © 1995 Wiley-Liss, Inc.     

Simultaneous reconstruction of head and neck defects following tumor resection and trismus release with a single anterolateral thigh donor site utilizing a lateral approach to flap harvest

Background: An anterolateral thigh (ALT) flap has gradually become the workhorse flap of reconstructions at different anatomical locations because of its reliability and versatility. In this study, we introduced the concepts: one is the ALT flap harvest from a lateral approach and the other is the reconstruction of extensive head and neck defects with a single ALT donor site. Methods: A lateral approach ALT flap was harvested in 13 patients who had buccal cancer and/or tumors of the lower lip combined with buccal trismus. Three types of ALT flaps (type I: two skin paddles, one pedicle; type II: two skin paddles, two pedicles; type III: one skin paddle, one pedicle) were used in one‐stage reconstructions of these extensive head and neck defects. Results: In our series, there were four type I, five type II, and four type III flaps. All flaps survived and no major postoperative complication occurred. Four of the 13 donor sites were repaired with a split‐thickness skin graft harvested from the contralateral thigh. The immediate interincisor distance increase was 21.4 and 16.5 mm at 1‐year follow‐up. Conclusions: Different types of ALT flap from a single donor site can be designed by means of a lateral approach; and the satisfactory results of reconstruction for extensive head and neck defects following the tumor resection and trismus release can be achieved. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.     

真皮下血管网薄皮瓣血运重建方式的实验研究

目的 探讨真皮下血管网薄皮瓣的成活机理。方法 分别在３组家兔背部形成真皮下血管网薄皮瓣、真皮下血管网皮片、传统随意皮瓣。运用组织透明技术,观察３组动物术后１～７ｄ、１４ｄ血管构筑变化的差异。结果 真皮下血管网薄皮瓣段存在一血管增生快速密集区－“中介蒂”,其血运重建过程明显早于传统随意皮瓣、真皮下血管网皮片。结论 本研究证实了“中介蒂”的存在,且这是真皮下血管网薄皮瓣可早期断蒂、有一定限度超长成活的     

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.     

Microvascular transfer of the rectus abdominis muscle and myocutaneous flap in rats

A rat microvascular free rectus myocutaneous flap model with a superior epigastric vessel pedicle is presented. The rectus muscle has a predictable ?flow-through”? axial vascular system consisting of superior and inferior epigastric vessels anastomosing under the fascial sheath, and six to seven musculocutaneous perforating branches to the skin. The superior epigastric artery and vein, averaging 0.45 mm and 0.5 mm in diameter, can be used as the vascular pedicle in muscle or myocutaneous flap transplantation. Eight muscle and 15 myocutaneous flaps were transplanted to the groin. The myocutaneous flaps averaged 3.5 cm by 1.2 cm in size; the pedicle length averaged 11 mm. The 5 day survival was 100% for muscle flaps and 67% for myocutaneous flaps. The rectus myocutaneous flap is believed to be the first true myocutaneous model in the rat. © 1993 Wiley-Liss Inc.     

Pedicled free flaps: indications in complex reconstruction

Pedicled free flaps are indicated when distant composite tissue is required for wound coverage and adjacent recipient vasculature is unsuitable for microvascular anastomosis. Carrier vessels from a noninjured extremity temporarily nourish the flap while neovascularization between the wound bed and the flap occurs. This process is augmented by intermittent occlusion of the vascular pedicle to prepare the flap for pedicle division. Rigid immobilization must be maintained to prevent avulsion of the flap. Laser Doppler monitoring of the flap during the ischemic training period permits division of the pedicle with confidence. This technique permits transfer of large flaps to compromised wounds with the advantage that the microvascular anastomoses can be performed safely away from the zone of injury. Provided immobilization can be maintained, flaps based on either a lower extremity or wrist carrier can reach virtually any area of the body.     

Y-V血管延长法在岛状皮瓣移位术中的应用

目的 介绍岛状皮瓣移位术中延长血管蒂的方法。评价其临床效果。方法 自1994年2月-2001年10月行Y-V血管延长岛状皮瓣移位术的患者16例,男10例,女6例;年龄19-45岁,平均26.8岁。皮瓣选取箩筐研究生蒂有“Y”形血管分支者,将与皮瓣血管蒂共干的另一条分支（“Y”形的另一臂）同时进行分离,在“Y”形分岔部的近侧结扎血管主干,以另一条血管为血供来源,血管蒂得以Y-V样延长,然后逆转修复创面。结果 血管蒂长度平均增加6cm,术后无血管危象发生65例皮瓣全部成活,色泽,质地与受区一致。结论 Y-V血管延长法不仅扩大了岛状皮瓣的应用范围。而且有利于移位皮瓣的成活,值得推广应用。     

The effect of single administration of vascular endothelial growth factor or L-arginine on necrosis and vasculature of the epigastric flap in the rat model.

OBJECTIVES: Vascular endothelial growth factor (VEGF) and nitric oxide (NO) produce vasodilation, induce angiogenesis, and improve survival of surgical flaps. We used the rat epigastric skin flap to study the effect of a single intra-arterial dose of VEGF or L-arginine, a substrate for NO production, on flap regional necrosis and pedicle dependence of flap perfusion. METHODS: In 30 Sprague-Dawley rats an 8 x 8 cm2 skin flap, consisting of four vertical zones marked A through D (right to left), based on the proximal right inferior epigastric vessels was raised. Subsequently, 1 ml of either saline (control, n =10), 5 microg VEGF (VEGF, n = 10), or 50 mg of L-arginine (L-arginine, n = 10) was injected into the arterial pedicle by cannulating the right saphenous artery, and the flap was resutured in place. After 8 days, the animals were perfused systemically with 15 microm coloured fluorescent microspheres before (blue) and after (yellow-green) ligation of the right inferior epigastric vascular pedicle. After sacrifice, the area of flap necrosis was measured in each zone by templates and weight-to-surface ratio, and the flap zones were harvested and processed for determination of fluorescence and blood flow. RESULTS: Administration of VEGF or L-arginine resulted in decreased total and regional (zone D) flap necrosis (ANOVA <0.001). The total and regional flap shrinkage was greater in the experimental groups (ANOVA <0.02). While VEGF and L-arginine decreased the percentage of necrosis in the zone most distal to the pedicle (ANOVA <0.01) only L-arginine diminished percentage of total flap necrosis (p = 0.04). In the VEGF group, total and regional flap perfusion did not change after pedicle ligation, but perfusion decreased significantly in zones B through D in the L-arginine treated rats. CONCLUSION: Single intra-pedicle administration of VEGF or L-arginine decreased necrosis of the epigastric skin flap at 8 days postoperatively, but flap shrinkage also increased in the zone with the greatest degree of necrosis. Perfusion data suggest that beneficial effects of VEGF and L-arginine on flap survival may be based on different mechanisms.     

VEGF Application on Rat Skin Flap Survival

ABSTRACT

Background: Induction of angiogenesis has been shown to be mediated by a number of glycoproteins called growth factors. Growth factors control the growth, differentiation, and metabolism of cells. Vascular endothelial growth factor (VEGF) is believed to be the most potent regulator of this process. The effect of its exogenous administration on the distal third of a long random skin flap was examined. Materials and Methods: Eighteen Wistar rats were divided into two groups of nine. Rats were anesthetized, and a skin flap, measuring 1.5 × 7.5 cm, was elevated at their dorsum. The flap was standardized by centering the pedicle between the lower angles of the scapulae and by using a frame with the previously mentioned dimensions. The length of the flap was five times greater than its width. In group A (n = 9), the flap was elevated, one milliliter of normal saline was injected subdermally, at the distal third, and it was sutured back at its original place. In group B (n = 9), the flap was elevated, injections of 10 μg of VEGF were administrated subdermally, at the distal third, and it was again sutured back. Rats were euthanized a week later and flaps were excised. All specimens were measured, photographed, put in formalin 10%, and were sent for image and histological analysis. Image analysis was used both for the estimation of viable area and for the calculation of mean vessel density per mm². Results: Necrotic areas of the flaps were clearly demarcated within a week's time. In group A, the mean flap survival percentage was 38.9%. In group B, the percentage was 80.4%. Histological analysis demonstrated angiogenesis in group B, with mean vessel density per mm² being higher in group B than in group A. Conclusions: Administration of VEGF injections at the distal part of a long random skin flap (length to width ratio 5:1) has been shown to improve the survival rate of the flap and thus contributing to the salvage of greater peripheral segment of the flap. Neovascularization induced by exogenous VEGF seems to be the biological mechanism, which leads to the improvement of flap survival.     

Clinical application and outcome of the internal mammary artery perforator (IMAP) free flap for soft tissue reconstructions of the upper head and neck region in three patients

Background : The fasciocutaneous internal mammary artery perforator (IMAP) island flap allows for superior esthetical and functional skin cover in the head and neck region in combination with limited donor site morbidity. Its modification as a free flap allows reconstruction of more cranial defects. Patients and methods : Three IMAP free flaps varying from 7 × 4 cm² to 10 × 6 cm² were transplanted in three patients with a mean age of 59 years (range, 54–69 years). Enhancement of the flap's vascular pedicle at least doubles the diameter of the internal mammary vessels to be anastomosed. Results : Coverage with excellent texture and color match was uneventfully obtained and the flaps' donor sites were primarily closed in all three cases. Conclusions : Our experience proves the consistent feasibility of successful transplantation of the IMAP free flap. Because of its characteristics, we suggest contemplating the use of this flap in the upper head and neck region. © 2010 Wiley‐Liss, Inc. Microsurgery, 2010.     

真皮下血管网薄皮瓣血管构筑变化与成纤维细胞生长因子的关系

为了探讨真皮下血管网薄皮瓣的成活机理，以兔为实验动物，在其背侧形成１５ｃｍ×３ｃｍ的真皮下血管网薄皮瓣，利用微循环显微镜、病理切片、组织化学染色等手段进行观察。结果表明真皮下血管网薄皮瓣术后远、中、近段血管构筑具有明显差别：近段同正常皮肤，中段为极度活跃的血管增生，远段为中度血管增生。皮瓣中段血管构筑的变化起一个“中介蒂”的作用，是皮瓣能够早期断蒂及超过传统长宽比例可以成活的基础。成纤维细胞生长因子是促使皮瓣血管构筑变化的重要因素之一。     

An ameliorated skin flap model in rats for experimental research.

There is a disagreement in the experimental design of random skin flaps owing to their vascular inconsistency. The definition of a reliable axial-pattern skin flap model is needed. The purpose of this study was to describe a new skin flap model to deal with entire drawbacks of existing random and axial pattern skin flap designs. This was accomplished by creating paired skin flaps including both skin and vascular pedicle on the dorsum of the same rat. This design was suitably termed as rando-axial flap. The present study offers a simple and reliable skin flap model with following advantages: (1) it has a predictable necrosis area, (2) it reveals a larger survival area (75 +/- 5%) when compared to other flaps in this study (Mann-Whitney U-test, p<0.001), (3) the vascular pedicle is consistent, (4) control and study flaps are placed on the same animal (5) it can be converted to a random, an axial or a free flap.