Pathophysiology of ischemic skin flaps: differences in xanthine oxidase levels among rats, pigs, and humans

Oxygen-derived free radicals have been implicated in a variety of diseases and pathologic processes, including ischemia reperfusion injury (IRI). Based on experimental work with rat skin-flap models, the enzyme xanthine oxidase (XO) has been proposed as a major source of free radicals responsible for tissue injury and flap necrosis. The presence of this enzyme is variable within different tissues of a specific species and between species. Xanthine oxidase levels in pig and human skin have not previously been reported. The activity of xanthine oxidase in the skin of rats (N = 16), pigs (N = 7), and humans (N = 8) was measured after varying intervals of ischemia and in the rat also following reperfusion. Control pig and human skin were found to contain minimal enzyme activity, almost 40 times less than that of the rat. In the rat, xanthine oxidase activity was stable throughout a prolonged period of ischemia, and a significant decrease in activity was found after 12 hours of reperfusion (p less than 0.05). In humans, xanthine oxidase activity was unaffected by ischemia time, and in the pig, it did not increase until 24 hours of ischemia (p less than 0.05). The potential sources of free radicals and the mechanism of action of xanthine oxidase and its inhibitor allopurinol in improving flap survival in different species are reviewed.     

When does a random flap die?

A random flap can be constructed, its circulation determined, and the ischemic portion identified. Left untreated for a period, the critical ischemia time, the ischemic portion will die and is clinically recognized several days later. What is not known is when this tissue, destined to die, actually dies. To ascertain this time, we compared the percent necrosis of a distal 3 x 3 cm segment of a 10 x 3 cm reverse McFarlane random flap with a known distribution of necrosis to the percent necrosis of the distal 3 x 3 cm of full-thickness skin grafts taken from a similar reverse McFarlane flap at 0, 4, 8, 12, and 16 hours after pedicle construction. Implicit in this experiment is the assumption that necrosis of the full-thickness skin grafts in excess of that of control animals represented skin no longer viable. Sometime between 8 and 12 hours, the percent necrosis of the full-thickness skin grafts surpassed that of the control, and it was concluded that this graft was dead prior to grafting. Thus it is suggested that critical ischemia time and death of the flap tissue are nearly identical, and the latter occurs at between 8 and 12 hours.     

Evaluation of the mechanism of vascular endothelial growth factor improvement of ischemic flap survival in rats

This study evaluated the effects of exogenous vascular endothelial growth factor (VEGF) on the regulation of cytokines in a rat dorsal ischemic skin flap model. Exogenous VEGF (1 microg/ml) was injected subdermally into the flaps of 12 rats before the flaps were sutured back in place. Another 12 rats with flaps received saline injections, as a control group. Biopsy specimens were obtained from the flaps treated with VEGF or saline solution, at positions 2.5, 5.5, and 8.5 cm from the distal edge of the flaps, at 12 hours (n = 6 for each group) and 24 hours (n = 6 for each group) after suturing of the flaps. Expression of cytokine, growth factor, and inducible nitric oxide synthase was measured. The results demonstrated that expression of tumor necrosis factor-alpha and nitric oxide synthase in the distal part of the VEGF-treated flaps was significantly decreased, compared with the control values, at 12 and 24 hours postoperatively. It was concluded that administration of exogenous VEGF could protect flaps from ischemia-reperfusion injury through the regulation of proinflammatory cytokines and the inhibition of cytotoxic nitric oxide production.     

Vascular endothelial growth factor expression in pig latissimus dorsi myocutaneous flaps after ischemia reperfusion injury

Exogenous administration of vascular endothelial growth factor (VEGF) improves long-term viability of myocutaneous flaps. However, endogenous expression of this substance in flaps following ischemia-reperfusion injury has not been reported previously. Endogenous production of VEGF was measured in myocutaneous pig latissimus dorsi flaps after ischemia-reperfusion injury. Latissimus dorsi myocutaneous flaps (15 x 10 cm) were simultaneously elevated bilaterally in six Yorkshire-type male pigs (25 kg). Before elevation, three flap zones (5 x 10 cm) were marked according to their distance from the vascular pedicle. After isolation of the vascular pedicle, ischemia-reperfusion injury was induced in one flap by occlusion of the thoracodorsal artery and vein for 4 hours, followed by 2 hours of reperfusion. The contralateral flap served as a control. Perfusion in each zone was monitored by laser Doppler flowmetry at baseline, during ischemia, and during reperfusion. At the end of the protocol, skin and muscle biopsies of each flap zone and adjacent tissues were obtained for later determination of VEGF protein levels. VEGF concentrations were quantified using the Quantikine human VEGF immunoassay. Skin perfusion was similar among all flap zones before surgery. Flow fell in all flaps immediately after flap elevation. After 4 hours of ischemia, blood flow in the ischemic flaps was significantly decreased (p < 0.05) compared with nonischemic control flaps. After 2 hours of reperfusion, flow in ischemic flap skin recovered to levels similar to those in control flaps. VEGF protein concentrations in muscle tissue exceeded concentrations in skin and decreased from zones 2 to 3 in control and ischemic flaps. No significant differences in VEGF concentrations between ischemic and control muscle zones were observed. However, the concentration of VEGF in all muscle zones was significantly higher (p < 0.05) than muscle adjacent to the flap. Concentrations in skin zones 1 and 2 were significantly higher (p < 0.05) in ischemic flaps than in control flaps, but levels in zone 3 (most ischemic flaps) showed no significant difference.     

The venous skin graft method for repairing skin defects of the fingers

A venous skin graft for the treatment of skin defects in a finger is described. This procedure involves taking a flap from the forearm together with the subcutaneous vein and anastomosing both ends of this vein to the digital artery and vein, respectively. Thirteen difficult finger wounds were resurfaced with such a venous skin graft. The sizes of the flaps ranged from 1.3 X 3.0 cm to 2 X 5 cm. The lengths of the veins taken were from 6 to 12 cm. Subcutaneous fat is thin, and there is good elasticity in the grafted flap.     

A study on the effectiveness of a thromboxane synthetase inhibitor (OKY-046) in increasing the survival length of skin flaps

In an experimental study to test the thromboxane (TX) synthetase inhibitor OKY-046, two random-pattern skin flaps, each measuring 15.5 x 2 cm, and caudally based, were elevated on the backs of rabbits, and the effect of the test drug on their survival length was evaluated. The results indicated that the survival length of the skin flaps was 4.5 +/- 0.2 cm in the control group and 6.8 +/- 0.3 cm in the OKY-046-treated group, hence exceeding the control value by more than 50 percent, which was statistically significant. A laser speckle flow-meter showed that the OKY-046-treated flaps had significantly greater blood flow as compared with the control group both at 1 and 48 hours after operation. Whereas the blood flow values were significantly lower at 48 hours than at 1 hour after operation in the control group, no such reduction was noted in the OKY-046-treated group. On the other hand, while plasma TXB2 was found elevated at 1 hour postoperatively in the control group, such a response to the surgical intervention was blocked and the plasma TXB2/6-keto prostaglandin (PG) F1a ratio was decreased in the OKY-046-treated group. These results clearly indicated that OKY-046 suppressed a plasma thromboxane elevation induced by surgery, it augmented the flap blood flow, and it thereby increased flap survival length, suggesting that the drug might be helpful clinically and that further investigation must be carried out concerning its application.     

A new flap design: neural-island flap

This report introduces the "neural-island flap" concept, which represents a consistent and reliable skin flap design supplied only by the intrinsic vasculature of a cutaneous nerve. In this study, the lateral femoral cutaneous nerve was selected as the pedicle of the neural-island flap, and a standard skin flap, which is the territory of the accompanying vessels (i.e., iliac branches of the iliolumbar artery and vein), was elevated on the lower dorsal region of the rats. In a total of 92 Wistar rats, three experiments were performed. In part I (n = 24), the vascular anatomy of the lateral femoral cutaneous nerve was established by the methods of dissection, microangiography, nerve mapping, perfusion with colored latex and India ink, and histologic analysis. In part II (n = 46), the role of the cutaneous nerve in supporting an acutely elevated skin flap was explored by creating five flap groups as follows: group 1, conventional flap (artery, vein, and nerve intact); group 2, neural island flap (only the nerve intact); group 3, neurocutaneous flap (vein and nerve intact); group 4, denervated flap (artery and vein intact); and group 5, skin graft. In part III (n = 22), the role of a preliminary surgical delay procedure to augment the survival of the neural island flap was investigated. Results of the anatomic studies indicated a consistent perineural vasculature by the accompanying iliolumbar artery. Skin flaps survived totally in groups where the artery and vein were intact, whereas mean survival rates for the neural island flap and the neurocutaneous flap were 38.2 +/- 3.1 percent and 44.5 +/- 3.8 percent, respectively (p > 0.05). Results of part III of the experiment demonstrated a significantly higher survival for the delayed neural island flap (94.5 +/- 5.5 percent) compared with the acutely elevated neural island flap (p < 0.05). The perineural and intraneural vessels were found to be greatly dilated after a delay procedure, demonstrated by direct observation, microangiography, histologic analysis, dye injection study, and scanning electron microscopy. On the basis of this promising series of experiments, a clinical technique was developed using the sural neural-island flap. The flap was used to reconstruct lower extremity defects in four cases. A delay procedure was accomplished in the first stage by elevating a fasciocutaneous flap from the midcalf region based on a posterior skin bridge and the sural nerve. After a 2-week delay period, a sural neural-island flap was created based on the nerve and transposed to the defect. Flap survival was complete in all cases, with a satisfactory result. The authors conclude that this report proves for the first time that a robust and reliable skin flap can be created pedicled only by the intrinsic vasculature of a cutaneous nerve, after a proper surgical delay. The so-created neural-island flap design offers two novel advantages: (1) a very narrow pedicle and (2) a pedicle without any restriction to a specific pivot point, in addition to the previously described unique advantages of preservation of a major artery and avoidance of microvascular anastomoses.     

A New Surgical Technique for Polysyndactyly of the Toes without Skin Graft

Reconstruction for polysyndactyly of the toes aims at cosmetic improvement. A previous method that uses a skin graft has inherent disadvantages of mismatched pigmentation between the graft and the surrounding skin and scar formation at the donor site. The authors' new improved surgical technique for the treatment of polysyndactyly of the toes does not require a skin graft and therefore avoids these problems. The authors designed a subcutaneous flap from the distal portion of a rectangular flap of skin from the dorsal side of the interdigital webbing and moved the former flap to the sidewall of the base of a toe. Both flaps are the same size; therefore, an interdigital space had to be of sufficient size to accommodate both of them. To ensure an adequate blood supply to the flap, careful handling of the subcutaneous flap is essential for success. This procedure can apply to polysyndactyly of the fourth, fifth, and sixth toes when the fourth and fifth toes adhere over the distal side of the distal interphalangeal joint and when the skin on the dorsal side of the fifth toe, regarded as the excessive one, is at lease twice the size of the dorsal rectangular flap. Ten patients with polysyndactyly of the toe were treated with this method. Aesthetically good results were obtained.     

Blood supply to osteocutaneous free fibula flap and peroneus longus muscle: prospective anatomic study and clinical applications.

From January of 1998 to December of 1999, a total of 24 fibula free flaps in 24 patients were evaluated in a prospective clinical study. Once the perforators were identified, they were dissected toward the parent vessel and labeled according to type. The soleus and flexor hallucis longus muscles of the fibula were dissected, and the proximal part of the pedicle was reached. Subsequently, the configuration of all muscular branches to the peroneus muscle was studied. The types of skin perforators of the peroneal artery were noted as septocutaneous, musculocutaneous, or septomusculocutaneous. A total of 86 perforators were identified in 24 legs. The average number of perforators per leg was 3.58 +/- 0.71. Among them, 22 were musculocutaneous, 31 were septomusculocutaneous, and were 33 septocutaneous. The septocutaneous branches were significantly more distal than the musculocutaneous and septomusculocutaneous perforators. Eight perforators were identified 25 cm distal from the fibular head and six were identified at 15 cm. Five perforators were then identified at each distance of 8, 12, 19, and 22 cm distal from the fibular head. The total number of muscular branches to the peroneus longus was 62, with an average of 2.58 +/- 0.45. Most muscular branches were found between 8 and 16 cm distal to the fibular head. Nine branches were identified at 13 cm distal to the fibular head, eight at 9 cm, and seven at 12 cm. The number of dominant branches with the largest diameter was seven at 13 cm distal from the fibular head, five at 12 cm, five at 16 cm, and two at 11 cm. In summary, when designing an osteocutaneous free fibula flap 10 to 20 cm from the fibular head, it is recommended that a soleus and flexor hallucis longus muscle cuff be included to incorporate these perforators. In contrast, when designing a flap 20 to 30 cm from the fibular head, it is possible to elevate the flap without incorporating the soleus or flexor hallucis muscles.     

The effect of nifedipine on skin-flap survival

Nifedipine, a calcium-channel blocker, is a peripheral vasodilator and has been shown to increase blood flow to skin. The hypothesis that nifedipine would thereby improve skin-flap viability was tested by comparing the extent of necrosis of long pedicle flaps in control and nifedipine-treated rats. Thirty male Sprague-Dawley rats were randomized to receive either 2.5 mg/kg nifedipine in chocolate PO t.i.d. or plain chocolate according to protocols. Serum nifedipine levels were determined by gas chromatography. Dorsal cephalad-based random vascular pedicle flaps (2 X 6 cm) were elevated, sutured to their beds, and photographed for computer-aided surface area determinations. The extent of distal flap necrosis was expressed as a percentage of the total flap area, and differences were studied by one-way analysis of variance. The differences between the mean percentages of necrosis at 1 and 2 weeks for the groups were not statistically significant. We conclude that nifedipine has no effect on the extent of necrosis of the random skin flap in the rat.     

Primary closure of radial forearm flap donor defects with a bilobed flap based on the fasciocutaneous perforator of the ulnar artery

To primarily repair a series of radial forearm flap donor defects, a total of 10 bilobed flaps based on the fasciocutaneous perforator of the ulnar artery were designed at the Chang Gung Memorial Hospital in Kaohsiung in the period from January of 2002 to January of 2003. All patients were male, with ages ranging from 36 to 67 years. The forearm donor defects ranged in size from 5 x 6 cm to 8 x 8 cm, with the average defect being 47 cm. One to three sizable perforators from the ulnar artery were consistently observed in the distal forearm and were most frequently located 8 cm proximal to the pisiform, which could be used as a pivot point for the bilobed flap. The bilobed flap consisted of two lobes, one large lobe and one small lobe. With elevation and rotation of the bilobed flap, the large lobe of the flap was used to repair the radial forearm donor defect and the small lobe was used to close the resultant defect from the large lobe. All bilobed flaps survived completely, without major complications, and no skin grafting was necessary. Compared with conventional methods for reconstruction of radial forearm donor defects, such as split-thickness skin grafting, the major advantage of this technique is its ability to reconstruct the donor defect with adjacent tissue in a one-stage operation. Forearm donor-site morbidity can be minimized with earlier hand motion, and better cosmetic results can be obtained. Furthermore, because a skin graft is not used, no additional donor area is necessary. However, this flap is suitable for closure of only small or medium-size donor defects. A lengthy postoperative scar is its major disadvantage.     

Enhanced neovascularization of rat tubed pedicle flaps with low perfusion of the wound margin

To study the role of ischemia due to low perfusion as the inciter of neovascularization, caudally based 3 X 9 cm skin flaps were created on the dorsum of 50 Sprague-Dawley rats. After injection of 0.2 ml 10% fluorescein, the animals were divided into two groups. In group I (n = 25), the distal margin of the flap tip was 1 cm proximal to the border of the fluorescence (good perfusion). In group II (n = 25), the flap was cut 1 cm distally in the nonfluorescent part (poor perfusion). The tips of the tubed flaps were transferred to a wound bed on the right flank. After 10 days, the pedicles were ligated, so that flap survival depended totally on the new vascular supply from the inset area of the flap. The flaps in group I showed a significantly higher rate of necrosis of 52.4 +/- 15.1 percent versus 1.7 +/- 1.4 percent in group II (p less than 0.0001), although the flap length in group I (5.85 +/- 1.16 cm) was less than in group II (7.15 +/- 0.95 cm; p = 0.0001). A nearly three times larger amount of tissue based on the new blood supply survived in group II compared to group I. Xerograms after injection of PbO2-gelatine on day 10 showed an increased ingrowth of blood vessels in group II. After excluding the delay phenomenon as the cause for the difference in necrosis rate, it is concluded that the only possible explanation is an enhancement of neovascularization by a perfusion gradient between the wound margins.     

Tissue engineering skin flaps: which vascular carrier, arteriovenous shunt loop or arteriovenous bundle, has more potential for angiogenesis and tissue generation?

This study was designed to clarify which vascular carrier, the arteriovenous shunt loop or the arteriovenous bundle, has more potential as a vascular carrier for an artificial skin flap in rats. An arteriovenous shunt loop was constructed between the femoral artery and vein using an interpositional artery (group I) or vein (group II) graft. For arteriovenous bundle groups, the femoral artery and vein were used and subdivided into two groups: distal ligation type (group III) and flow-through type (group IV). The vascular pedicle was wrapped with an artificial dermis and implanted beneath the inguinal skin for 4 weeks. For the control group, a folded sheet of artificial dermis without any vascular carrier was embedded. In experiment 1, the volumes of generated tissue within the artificial dermis were measured in the experimental and control groups (n = 5 in each group). In experiment 2, the origin of new blood vessels sprouting from the arteriovenous shunt loop and arteriovenous bundle were evaluated histologically. The volume of generated tissue in the shunt groups was significantly greater than that in the bundle groups (p < 0.01). However, the bundle groups also showed a great potential for producing new tissue. Serial histological studies showed that new capillaries were derived not only from the vasa vasorum of the femoral vessels but directly from the femoral vein in both the shunt and the bundle groups. This "sprouting" was extensively exhibited in the group III. Although the arteriovenous shunt loop showed a greater potential for producing new tissue and capillaries, the distal ligation type of bundle was thought to be an effective and practical vascular carrier for producing a tissue-engineered skin flap.     

The timing and nature of neovascularization of jejunal free flaps: an experimental study in a large animal model.

The present study was designed (1) to determine whether a free jejunal transfer in a large animal model can develop collateral circulation that is adequate to maintain viability after division of the pedicle and (2) to determine the earliest time pedicle ligation is safe after transplantation. A 15-cm jejunal segment was transferred to the necks of 18 dogs weighing 25 to 35 kg. The bowel segment was inset longitudinally under the skin on one side of the neck, partially covered by the neck muscles, and the mesenteric vessels were anastomosed to recipient vessels in the neck. The proximal and distal bowel stomas were exteriorized through skin openings 12 cm apart and matured. The dogs were subjected to ligation of the vascular pedicle at different intervals: postoperative day 7 (group I, n = 3), day 14 (group II, n = 5), day 21 (group III, n = 5), and day 28 (group IV, n = 5). Blood perfusion was measured in the proximal and distal bowel stomas before pedicle division (control) and 24 hours later using hydrogen gas clearance and fluorescein dye. Bowel necrosis was analyzed using planimetry. The bowel was also stained with hematoxylin and eosin and factor VIII, and new blood vessels were counted. Mean values (+/- standard deviation) were compared with control values for each test and with normal values in the intact bowel using analysis of variance with Neumann-Keuls post-hoc test for multiple comparisons. No jejunal free flaps survived when the vascular pedicle was divided 1 week postoperatively. Bowel survival was 60 percent at 2 weeks, 83 percent at 3 weeks, and 100 percent at 4 weeks. Hydrogen gas clearance values (ml/min/100 g) were 49.6 +/- 8.7 in the mucosa of the intraabdominal jejunum and 37.9 +/- 9.4 in the jejunum that was transferred to the neck before division of the pedicle. Twenty-four hours after pedicle division, hydrogen gas clearance values were 2.8 +/- 6.4 in group I (p < 0.05), 22.4 +/- 12.4 in group II, 23.9 +/- 9.3 in group III, and 34.2 +/- 7.5 in group IV. FluoroScan readings in the transferred jejunum were 201 +/- 7.2 in the control group, 9.3 +/- 2.8 in group I (p < 0.05), 79.1 +/- 10.6 in group II, 66.2 +/- 7.3 in group III, and 164 +/- 11.9 in group IV. New vessel formation as identified by factor VIII staining correlated with increasing bowel perfusion and flap survival rate. Bowel neovascularization, perfusion, and survival increased progressively 1 week after transfer. Significant portions of the transferred bowel will neovascularize and survive as early as 2 weeks postoperatively. However, a minimum of 4 weeks before ligation of the pedicle is necessary to maximize flap perfusion and guarantee survival.     

Distally based dorsal forearm fasciosubcutaneous flap

Use of a local flap is often required for the reconstruction of a skin defect on the dorsum of the hand. For this purpose, a distally based dorsal forearm fasciosubcutaneous flap based on the perforators of the posterior interosseous artery was developed. From 1997 until 2002, this flap was used to reconstruct skin defects on the dorsum of the hand in nine patients at Chonnam National University Medical School. The sizes of these flaps ranged from 10 to 14 cm in length and from 5 to 7 cm in width. The flaps survived in all patients. Marginal loss over the distal edge of the flap was noted in one patient. Three flaps that developed minimal skin-graft loss were treated successfully with a subsequent split-thickness skin graft. The long-term follow-up showed good flap durability and elasticity. The distally based dorsal forearm fasciosubcutaneous flap is a convenient and reliable alternative for reconstructing skin defects of the dorsum of the hand involving vital structure exposure. It obviates the need for more complicated and time-consuming procedures.     

Pharmacologic enhancement of rat skin flap survival with topical oleic acid

This study was instituted to investigate in a rat model the effect of topical coadministration of the penetration enhancer oleic acid (10% by volume) and RIMSO-50 (medical grade dimethyl sulfoxide, 50% by volume) on rat skin flap survival. A rectangular abdominal skin flap (2.5 x 3 cm) was surgically elevated over the left abdomen in 40 nude rats. The vein of the flap's neurovascular pedicle was occluded by placement of a microvascular clip, and the flap was resutured with 4-0 Prolene to its adjacent skin. At the end of 8 hours, the distal edge of the flap was reincised to gain access to the clips and the clips were removed. After resuturing of the flap's distal edge to its adjacent skin, the 40 flaps were randomly divided into four groups. Group 1 (control) flaps were treated with 5 g of saline, group 2 (dimethyl sulfoxide) flaps were treated with 2.7 g of dimethyl sulfoxide (50% by volume), group 3 flaps (oleic acid) were topically treated with 0.45 g of oleic acid (10% by volume), and group 4 (dimethyl sulfoxide plus oleic acid) flaps were treated with a mixture of 0.45 g of oleic acid (10% by volume) and 2.7 g of dimethyl sulfoxide (50% by volume) diluted in saline. Each flap was topically treated with 5 ml of drug-soaked gauze for 1 hour immediately after clip removal to attenuate reperfusion injury. Thereafter, drug was applied topically once daily for 4 more days. Digital photographs of each flap were then taken on day 6 and the flaps were then harvested. The percentage of skin survival in each flap was determined by computerized morphometry and planimetry. The mean surviving area of group 3 (oleic acid-treated flaps) was 23.60 +/- 4.19 percent and was statistically higher than that in group 1 (control, saline-treated flaps) at 7.20 +/- 2.56 percent. The mean surviving area of group 2 (dimethyl sulfoxide-treated flaps) at 18.00 +/- 5.23 percent and group 4 (oleic acid- and dimethyl sulfoxide-treated flaps) at 9.90 +/- 3.44 percent did not achieve statistically higher mean surviving areas than controls. A topical solution of oleic acid (10% by volume) caused a statistically significant increase in the survival of rat abdominal skin flaps relative to controls. Dimethyl sulfoxide and the two experimental drugs together did not increase the percentage of flap survival when given as a single 5-ml dose released from a surgical sponge at reperfusion for 1 hour and then daily for a total of 5 days. The reasons for the lack of response are unknown but may have included the technical difficulty of delivering an adequate dose of dimethyl sulfoxide topically and immiscibility between dimethyl sulfoxide and oleic acid. Further studies may be warranted.     

Osteocutaneous flap prefabrication based on the principle of vascular induction: an experimental and clinical study

Conventional osteomyocutaneous flaps do not always meet the requirements of a composite defect. A prefabricated composite flap may then be indicated to custom create the flap as dictated by the complex geometry of the defect. The usual method to prefabricate an osteocutaneous flap is to harvest a nonvascularized bone graft and place it into a vascular territory of a soft tissue, such as skin, muscle, or omentum, before its transfer. The basic problem with this method is that the bone graft repair is dependent on the vascular carrier; the bone needs to be revascularized and regenerate. The bone graft may not be adequately perfused at all, even long after the transfer of the prefabricated flap. This study was designed to prefabricate an osteocutaneous flap where simply the bone nourishes the soft tissues, in contrast to the conventional technique in which the soft tissue supplies a bone graft. This technique is based on the principle of vascular induction, where a pedicled bone flap acts as the vascular carrier to neovascularize a skin segment before its transfer. Using a total of 40 New Zealand White rabbits, two groups were constructed as the experimental and control groups. In the experimental group, a pedicled scapular bone flap was induced to neovascularize the dorsal trunk skin by anchoring the bone flap to the partially elevated skin flap with sutures in the first stage. After a period of 4 weeks, the prefabricated composite flaps (n = 25) were harvested as island flaps pedicled on the axillary vessels. In the control group, nonvascularized scapular bone graft was implanted under the dorsal trunk skin with sutures; after 4 weeks, island composite flaps (n = 15) were harvested pedicled on the cutaneous branch of the thoracodorsal vessels. In both groups, viability of the bony and cutaneous components was evaluated by means of direct observation, bone scintigraphy, measurement of bone metabolic activity, microangiography, dye injection study, and histology. Results demonstrated that by direct observation on day 7, the skin island of all of the flaps in the experimental group was totally viable, like the standard axial-pattern flap in the control group. Bone scintigraphy revealed a normal to increased pattern of radionuclide uptake in the experimental group, whereas the bone graft in the control group showed a decreased to normal pattern of radioactivity uptake. The biodistribution studies revealed that the mean radionuclide uptake (percent injected dose of 99mTc methylene diphosphonate/gram tissue) was greater for the experimental group (0.49+/-0.17) than for the control group (0.29+/-0.15). The difference was statistically significant (p<0.01). By microangiography, the cutaneous component of the prefabricated flap of the experimental group was observed to be diffusely neovascularized. Histology demonstrated that although the bone was highly vascular and cellular in the experimental group, examination of the bone grafts in the control group revealed necrotic marrow, empty lacunae, and necrotic cellular debris. Circulation to the bone in the experimental group was also demonstrated by India ink injection studies, which revealed staining within the blood vessels in the bone marrow. Based on this experimental study, a clinical technique was developed in which a pedicled split-inner cortex iliac crest bone flap is elevated and implanted under the medial groin skin in the first stage. After a neovascularization period of 4 weeks, prefabricated composite flap is harvested based on the deep circumflex iliac vessels and transferred to the defect. Using this clinical technique, two cases are presented in which the composite bone and soft-tissue defects were reconstructed with the prefabricated iliac osteomyocutaneous flap. This technique offers the following advantages over the traditional method of osteocutaneous flap prefabrication. Rich vascularity of the bony component of the flap is preserved following transfer (i.e. (ABSTRACT     

Differing flow patterns between ischemically challenged flap skin and flap skeletal muscle: implications for salvage regimens.

In this study, the authors tested the hypothesis that there is a significant difference in spatial patterns of reflow in skin as opposed to skeletal muscle after an ischemic insult. The authors believe that this pathophysiologic difference between the two flap types has significant implications for flap salvage strategies. Bilateral buttock skin flaps (10 x 18 cm) and latissimus dorsi myocutaneous flaps (10 x 20 cm) were elevated in Landrace pigs (n = 7). Flaps on one side of the animal were randomly assigned to 6 hours of arterial occlusion, with the contralateral side acting as control. At 15 minutes, 1 hour, and 4 hours after reflow, radioactive microspheres (15 microm) were injected into the left ventricle. After 18 hours of reperfusion, skin and muscle viability were estimated by intravenous fluorescein and soaking in nitroblue tetrazolium, respectively. Flow rates in the skin with an ischemia-reperfusion injury were significantly reduced (30 to 53 percent), at all time intervals, compared with controls. The flow rate in the fluorescent skin with ischemia-reperfusion injury of the latissimus dorsi flaps (0.037 ml/min/g at 15 min) was greater than in that of the buttock flaps (0.018 ml/min/g). The muscle flaps with ischemia-reperfusion injury had significantly higher flow rates than control muscle flaps at all time intervals studied (at 1 hour, 0.32 ml/min/g compared with 0.16 ml/min/g, respectively). In flap skeletal muscle, an early hyperemic phase during reperfusion maintains a significant blood flow to all regions, including the area of the flap that is destined for necrosis. In flap skin, however, there is a marked decrease in flow rates. These differences have important implications for the intravascular delivery of therapeutic agents to the damaged portions of the flap. Transdermal drug delivery systems should be explored as an alternative to intravascular regimens for the salvage of flap skin with ischemia-reperfusion injury.     

Increase in skin-flap survival by the vasoactive drug buflomedil

The effect of buflomedil to protect skin tissue from ischemia and necrosis was studied in random cutaneous flaps. Measurements were performed by intravital microscopy on the microcirculatory level of capillary perfusion in a flap model in the hairless mouse. In 30 hairless mice, single-pedicle flaps measuring 6 x 16 mm were raised perpendicular to the spine of the animal. This flap develops a reliable amount of necrosis at its distal edge over a period of 7 days. A group of 10 mice received intravenous injections of buflomedil in doses of 3 mg/kg per day diluted in 0.1 ml normal saline beginning 4 hours before flap elevation and for 6 consecutive days postoperatively. In addition, 10 further animals received the same treatment except that it was started 5 minutes after flap elevation. In 10 mice serving as controls, normal saline in equal volumes as in the experimental groups was applied. By means of intravital microscopy, functional vessel density (FVD) was determined in 2.5-mm increments from the flap's base to its distal edge at 1, 6, and 24 hours after elevation. Skin-flap survival was quantified by measuring the necrotic area on day 7 by means of digital planimetry. Functional vessel density was preserved in the distal flap of animals pretreated with buflomedil, revealing a higher functional vessel density at 10.0 mm (p less than 0.01), 12.5 mm (p less than 0.05), and 15.0 mm (p less than 0.001) from the flap's base as compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

De novo induction of island capsule flap by using two silastic sheets: Part 1. Generation

A new experimental model for de novo generation of an axial pattern island flap has been designed in a rat model. The purpose of this study was to make a sufficient vascular carrier, as an island capsule flap, with only vascular pedicles and addition of collagen fibers induced by foreign-body reaction. The femoral arteriovenous bundle was isolated and sandwiched between two 2.5 x 1.5 cm Silastic sheets. Eight weeks later, as a delay procedure, femoral vessels were ligated at the distal end of the Silastic sheets and the four margins of the sheets were divided except for the vascular pedicle. This capsule flap was raised as a secondary island flap connected only by its vascular pedicle, then it was sutured back in place. Ten days after the delay procedure, the upper Silastic sheet was removed and a full-thickness skin graft was performed on the capsular island flap. Animals were killed at 80 days. A total of 40 axial pattern capsulocutaneous flaps from 20 Sprague-Dawley rats were successfully achieved. Pathologic study revealed neovascularization, and abundantly impregnated vascular structures near the pedicle were observed with randomly developed collagen fibers. The skin graft took 100 percent on this newly formed capsular flap; therefore, the capsule structure was able to survive on its own and support skin grafts. This experiment, by using an isolated femoral artery and vein as the main pedicle, led to the formation of a capsule flap through a normal foreign body reaction between two Silastic sheet implants. This new flap can be used as a reliable vascular carrier for various needs with minimal donor morbidity.