Random Skin Flap Survival Research Articles

Improvement of a long random skin flap survival by application of vascular endothelial growth factor in various ways of local administration in a rat model

Background:Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein which plays a significant role in angiogenesis and vascular permeability. The effect of various ways of local administration of VEGF on random skin flap survival was studied, using flaps with a relatively high length (L) to width (W) ratio (5:1).Materials and Methods:An 1.5 × 7.5 cm dorsal skin flap with the pedicle orientated, centered, and remaining attached between the lower angles of the scapulae was elevated in 45 Wistar rats in different phases, depending on the group. Rats were divided in five groups of nine. In group A, injections of saline were administered, in equally divided spaces, into flap's fascia and transposed to a created skin defect. In group B, injections of VEGF were applied subdermally, in equally divided spaces, within the limits of a predesigned flap, a week prior to flap dissection and transposition. In group C, injections of VEGF were applied into a recipient bed's fascia just before flap raising and transposition. In group D, injections of VEGF were applied subdermally, only in the distal third of the flap and then the flap was transposed to a recipient area. Finally, in group E, injections of VEGF were applied in the flap intrafascially and in equally divided spaces and then again, the flap was transposed to a recipient area. A week after final flap raising and positioning, rats were euthanatised and flaps were excised. Specimens were photographed, measured, put in formalin 10% and were sent for histological and image analysis.Results:Mean flap survival percentage was 35.4% in group A, and 33.7% in group B. In groups C and D, the mean survival area was 56.3% and 80.4%, respectively. In group E, the mean flap survival percentage was 28.3%. Histological analysis demonstrated increased angiogenesis in groups C and D.Conclusions:VEGF application improved skin flap survival when injected subdermally in the distal third of a random skin flap or into the fascia of a recipient area even though the length-to-width ratio was high.

The Effect of Angiotensin (1–7) on Survival of Random Pattern Skin Flaps With Nicotine-Induced Ischemia in Rats

The purpose of this study was to reveal the effect of angiotensin (1-7) on survival of random pattern, nicotinized, ischemic flap model in rats. We used female Sprague Dawley rats weighing between 250 and 300 g. The study was performed on 3 groups each of them was consisted of 30 rats (control [C], angiotensin (1-7) [A] and vehicle [V]).While group C was subjected to 1 mL saline subcutaneous injection once daily for 28 days, groups A and V were nicotinized by 2 mg/kg nicotine subcutaneous injection, twice a day. At the end of this period, McFarlane random flap was constructed in all rats. No drug was applied to the flap bed in the group C, whereas for group A angiotensin (1-7) (A [1-7]) was delivered and a vehicle without an active ingredient was applied to the group V.Following surgery, immediately, Na-fluorescein diffusion tests were performed on 10 subjects of every group and necrotic areas were determined by millimetric paper method. After this, for determining angiogenesis, 10 subjects were killed from each group on the second day and fourth day. Finally, on the seventh day, necrotic areas were measured in 10 subjects of each group. They were then killed after photographs were taken. Specimens were collected from distal and critical zones of flaps, in all the groups, for immunohistochemical and histopathologic analyses. Macroscopic measurements revealed equal ischemic areas for groups A and V in 30 minutes which were both larger than those of the group C (P < 0.005). Measurements performed on the seventh day showed a significant decrease of ischemia, which advanced to necrosis in the group A (P < 0.005). Groups V and C showed a direct progress to necrosis without changes in ischemia levels. Microscopic analysis exhibited a statistically significant increase in the number of microvascular structures and diameters of mature vascular structures in the group A compared with those of groups C and V (P < 0.005). A (1-7) increased vasodilatation in nicotinized flaps, triggered angiogenesis in the first 2 days, and contributed remarkably to the flap survival.

The effect of hyperbaric oxygen therapy on the survival of random pattern skin flaps in nicotine-treated rats

Previous studies have shown that nicotine increases the risk of necrosis in skin flaps. We investigated the effect of hyperbaric oxygen (HBO(2)) treatment on the survival of random skin flaps in nicotine-treated rats. Thirty-two Sprague-Dawley rats were divided into four groups with eight rats in each group. Group 1 (n=8) was the control, group 2 (n=8) received HBO(2) treatment without being exposed to nicotine, group 3 (n=8) received nicotine and group 4 (n=8) received HBO(2) treatment with exposure to nicotine. The rats in the nicotine-treated groups were prepared by treating them with nicotine for 28 days. At the end of the 28th day, standard McFarlane-type random skin flaps were lifted from the backs of all the rats. In groups 2 and 4, HBO(2) treatment started at the 30th min following the surgery and continued once a day for 7 days. The flap survival rates and histopathological evaluation results related to neovascularisation and granulation tissue formation were significantly better in the HBO(2)-treated groups (groups 2 and 4) than in the groups that did not receive HBO(2) treatment (groups 1 and 3) (p < 0.05). The flap survival rates, neovascularisation and granulation tissue formation were highest in group 2 and lowest in group 3 (p ≤ 0.001). No significant difference was observed between group 4, which received HBO(2) treatment with nicotine exposure, and the control group (group 1) (p > 0.05). In conclusion, our study demonstrates that HBO(2) treatment has a positive effect on flap survival in nicotine-treated rats.

Thermography‐measured effect of capsaicin, methylprednisolone and mitomycin on the survival of random skin flaps in rats

This study was designed to determine if steroids, capsaicin and mitomycin improved skin flap survival in rats, and it has confirmed that thermography is an effective method to measured skin flap vitality. Forty female Wistar rats were randomised into four groups. A standardised full thickness inferiorly based dorsal random-pattern skin flap was raised, and a gelatine sponge was placed before suturing between the flap and its recipient bed, soaked with 0.9 % saline in the control group and with capsaicin, methylprednisolone and mitomycin in the experimental groups. Vitality of the flap and of the survival area was measured by infrared thermography. Methylprednisolone statistically significant decrease skin flap necrosis, approximately 56%, when compared with controls (P< 0.05). Corticosteroids applied subcutaneously in a single dose on a gelatine sponge produced a statistically significant improvement of the survival of random skin flaps in rats, whereas capsaicin and mitomycin showed no improvement.

The effect of adipose-derived stem cells on viability of random pattern skin flap in rabbits

To explore the effect of the adipose derived stem cells (ADSCs) on the survival of random pattern skin flap in rabbits. ADSCs were isolated from fresh human fat and expanded in vitro for five passages. Then the characterization of ADSCs were determined by their CD marker profile and their ability to differentiate into osteogenic, adipogenic and chondrogenic lineages. On the back of the rabbits, two symmetric cephalic-based random pattern skin flaps were designed (6 cm x 2 cm). The right flaps were used as experimental groups with the contra-side flaps as control group. Human ADSCs were pre-labeled before seeding with fluorescent 3, 30-dioctadecyloxacarbocyanine perchlorate (DiO) dye. The experimental flaps evenly received 5-point injection of 2 x 10(6)Dio-labeled ADSCs resuspended in 0.5 ml of serum-free DMEM, while only 0.5 ml medium was injected into the control flaps. Seven days later, the survival rate of flaps was evaluated. The flaps underwent frozen section and were observed under the laser scanning confocal microscope to detect the fluorescence imaging. Flaps also underwent HE staining and were observed under light microscope to detect the vascular density. Compared with control group, there was a significant increase of flap survival rate in the experimental group (P < 0.01). Histological analysis also demonstrated a statistically significant increase in capillary density in the experimental group. It suggests that ADSCs have a better immune compatibility and potential for enhancing the blood supply of random pattern skin flaps.

Effect of hirudin on random skin flap survival in rats

To investigate the effect of Hirudin on random skin flap survival in rats. 24 SD rats were randomly divided into control group and experimental group. The "McFarlane flap (3 cm x 9 cm)" rat models were established on the rat dorsum. 3 ml Hirudin (30 ATU) was injected into the flap in the experimental group, while 3 ml saline in the control group. The injection was performed for 7 days. The flap survival area in the two groups was measured. The tissue samples were taken from proximal (I), middle (II) and distal (III) portions of flaps for histologic study. The VEGF and bFGF expression was also detected with immunohistochemistry method. 7 days after operation, the flap survival rate was (69.52 +/- 3.23)% in the experimental group, while (50.36 +/- 2.37)% in control group, showing a significant difference between the two groups (P < 0. 01). In the middle portion, tissue edema and infiltration of neutrophils in experimental group was markedly slighter than that in control group. The VEGF and bFGF expression and neovascularization was enhanced markedly in experimental group. Hirudin can increase the survival of random pattern skin flaps. It may increase the VEGF, bFGF expression through a series of complex regulatory pathway. Then flap neovascularization is promoted and the flap blood supply is increased.

The effects of basic fibroblast growth factor-fibrin glue on the survival of the random pattern skin flap

Objective To explore the effects of basic fibroblast growth factor-fibrin glue (bFGF-FG) on the survival of early pedicle division of random pattern skin flap. Methods bFGF-FG were prepared and sprayed under the random pattern skin flaps.The pedicles were divided 4 days later. 10 days later,flap survivals and the microvascular densities of each group were determined.Results The flap survival rate were (75.6 ± 8.9) %,(68.3 ± 9.3) % and (51.4 ± 11.2) % respectively, and the microvascular densities were (24.15 ± 6.42 ) mm2, ( 20.6 ± 4.56 ) mm2 and ( 15.95 ± 3.18 ) mm2 respectively .There was significant difference statistically.Conclusions The bFGF-FG can increase the survival of early pedicle division of random flap more effectively. Key words: Basic fibroblast growth factor; Fibrin glue; Random pattern skin flap

The effect of Hirudoid on random skin-flap survival in rats

One of the main fields of research in flap surgery is to increase the viability of flaps. Many materials have been tested for this purpose. This study shows that topical application of Hirudoid, an organoheparinoid, increases flap survival of dorsal flaps in rats. Hirudoid was used topically every day in eight of 16 rats in which 10x3-cm dorsal flaps were prepared. The flaps were taken for analysis on the 10th day. Analysis of the flaps was performed using digital measurement and scintigraphy. Analysis revealed that the flap necrosis area was smaller in the Hirudoid group compared to the control group. In addition, the area exhibiting radioactive uptake in scintigraphy was greater in the treatment group. Topical administration of Hirudoid may significantly improve flap survival.

The effects of montelukast on random pattern skin flap survival: An experimental study in rats

Background: A variety of methods to improve skin flap survival, including the use of pharmacologic agents, have been intensively investigated. Decreasing neutrophil-mediated inflammation and tissue injury has been reported to be effective in improving flap survival. Montelukast is a selective reversible cysteinyl leukotriene receptor-1 antagonist that has been found to have protective effects against renal ischemia reperfusion injury and burn-induced oxidative injury of the skin in rats. However, its effects on skin flap survival have not been previously reported. Objective: The aim of this study was to investigate the effects of montelukast on neutrophil-mediated random pattern skin flap survival. Methods: Male Sprague-Dawley rats weighing 230 to 250 g were randomly divided into 2 groups—the montelukast-treated group and the control group. Caudally based rectangular random pattern skin flaps 3 × 9 cm were elevated on the backs of the rats. The flaps were sutured into their original places. In the montelukast group, 1 mL of solution containing 10 mg/kg montelukast was administered intraperitoneally (IP) 30 minutes before surgery and then daily for 6 days. In the control group, 1 mL of saline was administered IP 30 minutes before surgery and then daily for 6 days. To observe the effects of montelukast, myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration, was measured from extracted skin tissue 12 hours after flap elevation. Flap viability was evaluated 7 days after surgery by measuring necrotic flap area and total flap area. Results: Sixteen rats (mean [SD] weight, 240.6 [6.6] g) were equally divided between the 2 groups. All rats survived throughout the study period. Mean (SD) MPO activity in flap tissue was significantly lower in the montelukast group than in the control group (14.57 [2.33] vs 21.28 [4.86] U/g protein; P = 0.005). The percentage of necrotic flap area was significantly lower in the montelukast group than in the control group (17.17 [7.95] vs 37.51 [10.72]; P = 0.001). Conclusion: This small, experimental, in vivo animal study found that montelukast was associated with both lower MPO activity and a lower percentage of necrotic random pattern skin flap area. Future studies are needed to clarify these findings.

Effects of nebivolol on skin flap survival: A randomized experimental study in rats

Background: Skin flaps are among the basic treatment options in the reconstruction of soft tissue defects. To improve skin flap survival, a variety of methods, including pharmacologic agents, have been investigated. The effectiveness of anticoagulants, antioxidants, anti-inflammatory drugs, and vasodilatory drugs in improving flap survival has been studied. Nebivolol is a new-generation selective β 1-adrenoreceptor blocking agent that has vasodilatory, antithrombotic, antioxidative, and anti- inflammatory effects. Objective: The aim of this experimental study was to investigate the effects of nebivolol (50 mg/kg/d) on random pattern skin flap survival in rats. Methods: Male Wistar rats weighing 290 to 310 g were randomly divided into 2 groups—the nebivolol group and the control group. Random patterned, caudally-based, ~3 × 10-cm skin flaps were elevated on the back of each rat. In the nebivolol group, nebivolol 50 mg/kg/d (1 mL, of a racemic solution of nebivolol) was administered orally 2 days before surgery to reach steady-state drug blood concentrations and was continued for 6 days. In the control group, 1 mL/d of sterile saline solution was orally administered 2 days before surgery and was continued for 6 days. To observe the effects of nebivolol, cutaneous blood flow was examined using a laser Doppler flow-meter before and after surgery on days 1, 3, 5, and 7, and flap tissue, malondialdehyde (MDA) and glutathione (GSH) concentrations, and superoxide dismutase (SOD) activity were measured 7 days postsurgery. Flap viability was evaluated 7 days after surgery by measuring necrotic flap area and total flap area. Results: All 20 rats (nebivolol group, n = 10; control group, n = 10) survived throughout the study period. Mean (SD) MDA concentration was significantly lower in the nebivolol group than in the control group (69.25 [5.82] vs 77.67 [6.87] nmol/g tissue; P = 0.009). GSH concentration was significantly higher in the nebivolol group than in the control group (2.14 [0.15] vs 1.88 [0.22] nmol/mg tissue; P = 0.004). SOD activity was significantly greater in the nebivolol group than in the control group (49.28 [5.49] vs 42.09 [4.95] U/g tissue; P = 0.007). The percentage of the flap that was necrotic was significantly lower in the nebivolol group than in the control group (40.27 [4.08] vs 48.87 [6.35]; P = 0.007). Conclusions: This small, experimental, in vivo animal study found that nebivolol was associated with reduced necrotic random pattern skin flap area. Further studies are needed to clarify these findings.

Effect of Aspirin and Heparin on Random Skin Flap Survival in Rats

BACKGROUND Aspirin and heparin are commonly given to patients undergoing microvascular procedures to increase flap survival and patency, yet there is scant information concerning the effect these flaps have on nonmicrovascular flaps. OBJECTIVE The objective was to obtain baseline values concerning the effect of aspirin and heparin on the viability of standardized flap tissues. METHODS AND MATERIALS One hundred rats were divided into five groups receiving high-dose aspirin, low-dose aspirin, high-dose aspirin in combination with heparin, and heparin alone and the final group were controls. The viability of the tissue was measured at 1 week by fluorescein florescence. RESULTS There was significant improvement in flap survival in the high-dose aspirin and high-dose aspirin combination groups. CONCLUSIONS It appears that high-dose aspirin increases survival of ischemic flap tissue irrespective of the presence of microvascular anastomosis and may be of clinical benefit in all flap surgery.

Effect of Aspirin and Heparin on Random Skin Flap Survival in Rats

Aspirin and heparin are commonly given to patients undergoing microvascular procedures to increase flap survival and patency, yet there is scant information concerning the effect these flaps have on nonmicrovascular flaps. The objective was to obtain baseline values concerning the effect of aspirin and heparin on the viability of standardized flap tissues. One hundred rats were divided into five groups receiving high-dose aspirin, low-dose aspirin, high-dose aspirin in combination with heparin, and heparin alone and the final group were controls. The viability of the tissue was measured at 1 week by fluorescein fluorescence. There was significant improvement in flap survival in the high-dose aspirin and high-dose aspirin combination groups. It appears that high-dose aspirin increases survival of ischemic flap tissue irrespective of the presence of microvascular anastomosis and may be of clinical benefit in all flap surgery. The authors have indicated no significant interest with commercial supporters.

Dipyrone Increases the Blood Flow of Arterial Dorsal Skin Flaps

Findings have shown that dipyrone has a beneficial effect on skin flap survival. A pharmacologic explanation for this effect points to its vascular smooth muscle-relaxing effect. This study evaluated the effect of dipyrone on blood flow and thus survival of rat random dorsal skin flaps. For this study, 27 male Wistar albino rats were randomly assigned to control (treated with sterile saline) and treatment (treated with dipyrone 100 mg/kg) groups. A random dorsal skin flap measuring 4 x 10 cm was raised in each animal. The edges of the flap were sutured back into their original place. Dipyrone treatment continued at 100 mg/kg per day during the 7-day observation period. Blood flow was recorded by laser Doppler preoperatively (baseline), immediately after the flap was sutured back to its original position (acute), and on postoperative day 7. The degree of necrosis was evaluated by the grid method on day 7. Mean percentage necrosis and minimum laser Doppler readings were compared between the two groups. A significant increase in blood flow was observed in the dipyrone group at the acute phase but not on postoperative day 7. The percentage of the necrotic area was lower in the treatment group. However, it did not reach the significance level (p = 0.09). Dipyrone significantly increases [corrected] skin blood flow at the acute phase of flap elevation although the necrotic area does not reach the significance level.

Acute Remote Preconditioning Augments Random Skin Flap Survival, But Not Recipient-Bed Isolated Flaps In Rats

This study proposes that acute remote preconditioning (ARIP) can effectively enhance random skin flap survival.The study was a randomized controlled trial using male sprague-Dawley rats as subjects. For acute remote preconditioning, left hindlimb ischemia was achieved by clamping the femoral artery and vein.After 1 hour's ischemia, the limb reperfusion was done for 30 minutes. Then, a 3by 9cm dorsal caudal-based, random pattern skin flap was elevated and reaproximated for flap survival studies. Thirty rats were divided into three groups of 10 rats each. The first group had only the flap raised, while the second and third groups had acute remote preconditioning protocol before the flap elevation. In the third group, a silicone sheet was inserted beneath the flap in order to prevent neovascularisation from the bed. The amount of flap necrosis was measured on the seventh postoperative day. ARIP (acute remote ischemic preconditioning) group had the most improved skin flap survival rate, and the flap survival rates between the ARIP+silicone sheet and control groups was not statistically different (p>0.05). These findings indicate that remote ischemic precontioning enhances random skin flap survival, when it is performed just before the flap harvest and the isolation of recipient bed abolishes this ameloriating effect.

A New Agent for Flap Survival – Hippophae Rhamnoides L. (Sea Buckthorn): An Experimental Study in Rats

Hippophae rhamnoides L. (sea buckthorn) is a member of the Elaeagnaceae family, and is a temperate bush native to Europe and Asia. The antioxidant activity of H rhamnoides L. has been shown in vitro cell culture and animal studies. Different fractions of H rhamnoides L. fruits inhibit 2,2-azobis-(2,4 dimethylvaleronitrile) and ascorbate iron-induced lipid peroxidations in vitro. H rhamnoides L., as well as vitamin E, decrease the malondialdehyde content in hyperlipidemic rabbit serum-cultured smooth muscle cells. The aim of the present study was to investigate, in a rat model, the potential effect of H rhamnoides L. on survival of random pattern skin flaps. For this purpose, 30 Wistar Albino rats were used, and a McFarlane-type caudally based skin flap was created on the dorsum of the rat (2.5 cm × 8 cm). Rats were divided into three groups: one control (group A) and two treatment groups (groups B and C). H rhamnoides L. was administered orally to the experimental groups: group B received a single 15 mg/kg dose per day and group C received 15 mg/kg twice per day. The areas and lengths of flap necrosis were measured in each group. The extent of necrotic flap areas were evaluated as length and area of total flap area, and differences were studied by Student's t tests. The areas and lengths of necrosis of skin flaps decreased depending on H rhamnoides L., but viability of the flaps treated with 15 mg/kg/day was not significantly different from the control group. The rats receiving H rhamnoides L. 15 mg/kg twice per day had the highest flap survival rate (P<0.001). In conclusion, H rhamnoides L. may have a dose-dependent effect to increase flap survival in random skin flaps.

Improved Survival of Ischemic Random Skin Flaps Through the Use of Bone Marrow Nonhematopoietic Stem Cells and Angiogenic Growth Factors

Surgical skin flaps are frequently used in plastic and reconstructive surgery to repair acquired or congenital defects. Necrosis is a common complication associated with these flaps postoperatively as a result of inadequate blood supply. Stem cells are precursor cells with the potential to differentiate into more specialized cells. Angiogenic factors act to direct cellular differentiation and organization to form new vascular elements. Our theory was that the combination of angiogenic growth factors with stem cells derived from the subject preoperatively would augment neovascularization, thereby increasing blood supply to the flap, which may ultimately improve flap survival. In phase I, 40 Lewis rats were randomized into 4 groups of 10. Random dorsal skin flaps were elevated and treated at the same time. The first group was injected with only medium, the second with stem cells, the third with stem cells and angiogenic factors, and the fourth with angiogenic growth factors. Millimetric measurements of flap viability at 7 and 14 days did not show any statistically significant differences between the studied groups. In phase II, 24 rats were also randomized into 4 groups of 6, but this time were treated 1 week before flap elevation. The viability measurements showed an increased rate of viability in the group in which stem cells and the angiogenic factors were administered simultaneously (84.5% +/- 3.2%) as compared with the unmodified control group (62.6% +/- 7.3%) or to the groups in which only precursor cells (60.4% +/- 7.9%) or angiogenic factors (62.3%+/- 10.1%). Increased blood supply brought by these manipulations is believed translated to increased tissue flap survival. Punch biopsies showed that "green fluorescent protein"-labeled precursor cells was noted to form luminal structures in the treated flaps. The vascular cast of all flaps was filled with Mercox plastic resin. After euthanasia, the soft tissues of the harvested flaps were dissolved and the remaining vascular cast was weighted. The weight-based ratio of the vascular composition was determined. The flaps injected with both stem cells and angiogenic factors showed higher values. We conclude that the administration of bone marrow stem cells with angiogenic factors 1 week before flap creation improves the survival of ischemic random skin flaps.

The influence of sildenafil on random skin flap survival in rats: an experimental study

Sildenafil (Viagra ®), a selective and specific inhibitor of cyclic guanosine monophosphate (cGMP) phosphodiesterases (PDEs), is currently marketed for the treatment of erectile dysfunction. Sildenafil is a potent and highly selective PDE-V inhibitor and enhances smooth muscle relaxation in human. Systemic arterial and venous smooth muscle cells contain PDE-V and nitric oxide (NO) which is a major mediator of relaxation of the smooth muscle cell. The aim of the present study is to investigate, in a rat model, the potential effect of sildenafil on survival of random pattern skin flaps. For this purpose, 32 Sprague-Dawley rats were used and a McFarlane-type caudally based skin flap was designed on the dorsum of the rat (2.5×8 cm). Rats were divided into four groups: One control (Group D), and three treatment groups (Groups A, B, C). Sildenafil was administered orally to the experiment groups; Group A: 3 mg/kg/single dose a day, Group B: 10 mg/kg/single dose a day and Group C: 10 mg/kg/twice dose a day. The areas of flap necrosis were measured in each group. The extent of viable flap areas were expressed as a percentage of total flap area, and differences were studied by Completely Randomised Experimental design. The areas of necrosis of skin flaps decreased depending on sildenafil dose, but viability of the flaps treated with 3 mg/kg/day was not different than the control group. The flaps receiving 2×10 mg/kg/day sildenafil gave the highest ( P<0.01) survival rate. As a conclusion, sildenafil may have a dose dependent effect to increase flap survival in random skin flaps.

Effects of low-power laser irradiation on survival of random skin flap in rats

This research was designed to study the effects of low-power helium–neon (He–Ne) laser irradiation on random skin flap survival in rat. Fifty 50 male rats were randomly divided into five groups. On the dorsum of each rat, one full thickness random skin flap which contained no specific vessel was elevated. Groups 1 to 4 were exposed to different models of a low-power He–Ne laser. Group 5 rats received no laser treatment and were considered as the control group. The energy density of the He–Ne laser used was 0.2 J/cm2. Immediately after surgery and at day 7, the surface area of all flaps was determined. Histological and tensiometrical studies on the surviving part of the flaps were also performed. The data obtained were analyzed by ANOVA. The results showed a significant difference in the surface area of survival parts of flaps and density of blood vessels on day 7 between group 3 rats and the other groups (P=0.0188, P=0.0455). Low-power He–Ne laser irradiation of flaps without recognized blood vessels in rats, reduced vasospasm, produced vasodilation, and caused a significant increase in the surviving surface area.

Protective effect of melatonin on random pattern skin flap necrosis in pinealectomized rat.

Random pattern skin flaps are still widely used in plastic surgery. However, necrosis in the distal portion resulting from ischemia is a serious problem, increasing the cost of treatment and hospitalization. Free oxygen radicals and increased neutrophil accumulation play an important role in tissue injury and may lead to partial or complete flap necrosis. To enhance skin flap viability, a variety of pharmacological agents have been intensively investigated. The aim of this study is to test the effects of melatonin, the chief secretory product of the pineal gland and a highly effective antioxidant, on random pattern skin flap survival in rats. Herein, to investigate the physiological and pharmacological role of melatonin on dorsal skin flap survival. Pharmacological (0.4, 4 and 40 mg/kg) levels of melatonin were given intraperitoneally (i.p.). For this, pinealectomized (Px) and sham operated (non-Px) rats were used. The effects of melatonin on levels of malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH) and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were measured in the skin flap. The ratio of skin flap necrosis was compared among the experimental groups by using planimetry. MDA and NO levels were found to be higher in Px than non-Px rats; while GSH levels and GSH-Px, and SOD activities were reduced. Melatonin administration to Px rats reduced MDA and NO levels and increased GSH, GSH-Px, SOD levels. Melatonin also reduced the ratio of flap necrosis determined by using planimetry and supported through the photography. In conclusion, these results show that both physiological and pharmacological concentrations of melatonin improve skin flap viability.

Heat shock protein and high-dose aspirin: effects on random skin flap survival in a rat model.

The heat shock response is known to have a protective effect against flap ischemia. It has been shown that heat shock protein (hsp) expression can be augmented in vivo with the administration of high-dose aspirin before heat treatment. The authors hypothesized that administration of aspirin before hsp induction through heat stress would enhance further the protective effects of the heat shock response against skin flap ischemia. They used a random dorsal skin flap model in 32 rats divided into four groups (N = 8 each): control, heat shock, aspirin plus heat shock, and aspirin. Before surgery, rats in the two heat shock groups were placed in a 45 degrees C water bath until core body temperature measured 42 degrees C, and they were maintained at 42 degrees C for 15 minutes. Rats in the two aspirin groups received a single oral dose of aspirin (100 mg per kilogram) 1 hour before heat bath or surgery. Immunohistochemistry confirmed hsp expression in the two heat groups. Skin flap survival was improved significantly (p < 0.05) in the heat shock (55%), aspirin plus heat shock (58%), and aspirin (60%) groups when compared with controls (45%). Contrary to their hypothesis, aspirin combined with hsp induction did not offer greater protection from ischemia than hsp induction alone (p > 0.05). However, high-dose aspirin administration alone did improve skin flap survival when compared with controls. Future studies are needed to investigate further the role of pharmacological therapy combined with hsp induction in improving skin flap survival and to delineate the dose-response relationship between aspirin and hsp.