Flap Survival In Rats Research Articles

Effect of platelet glycoprotein IIb/IIIa receptor antagonist on survival of epigastric island flaps in rats with total venous occlusions

We evaluated the effect of tirofiban hydrochloride on the survival of epigastric island flaps in rats that had had all the veins occluded. Male Wistar Albino rats were randomly assigned to control (treated with sterile saline) and experimental (treated with tirofiban hydrochloride 1 mg/kg intravenously) groups. An epigastric island skin flap 3x6 cm was raised in each rat. All veins that drained the flap were ligated to give total venous occlusion. Blood flow was recorded by laser Doppler preoperatively (baseline), immediately after the flap had been sutured back to its original position (acute) and on postoperative days 1 and 3. The degree of necrosis was evaluated on day 3. Mean percentage necrosis and minimum laser Doppler values were compared in the two groups. Total necrosis was evident on day 1 in the control group and on day 3 in the experimental group. Macroscopic evidence was confirmed by histopathological examination. There were appreciable differences in blood flow and in the necrotic area of the flap in the experimental group compared with the control group on both days 1 and 3. Tirofiban hydrochloride might be effective in this flap model.

Depletion of Glutathione by Buthionine Sulfoximine Decreases Random-Pattern Skin Flap Viability in Rats

Glutathione (GSH) is one of the most highly concentrated intracellular antioxidants. Exogenous GSH has been shown to increase random-pattern skin flap survival. However, the effects of endogenous GSH depletion on random-pattern skin flap viability have never been studied. To evaluate the effects of systemic glutathione depletion on random-pattern skin flap survival in rats, 28 Wistar albino rats were divided into control, sham, and BSO (buthionine sulfoximide, a selective inhibitor for gamma-glutamylcysteine synthetase) groups. Dorsal, cranial-based random-pattern skin-flaps were elevated and the percentage of flap necrosis was measured in all rats at the postoperative day 7. BSO-treated rats showed increased skin flap necrosis when compared with untreated animals (P < 0.001). High-dose BSO treatment group had more clinically evident necrosis than low dose group (P < 0.05). This study reveals the importance of endogenous GSH for random skin-flap viability.

Effects of clopidogrel on survival of rat skin flaps

Clopidogrel is a thienopyridine derivative that is chemically related to ticlopidine, which irreversibly inhibits platelet aggregation by selectively binding to adenylate cyclase-coupled adenosine diphosphate receptors on the platelet's surface. In animal models, clopidogrel has been shown to reduce the incidence of both arterial and venous thrombi. In the present study the effects of clopidogrel on the survival of rat epigastric island flaps was researched. Epigastric island flaps of 7x7cm were raised from symphisis pubis to arcus costa with the panniculus carnosus. The experimental group received seven doses of 25mg/kg clopidogrel postoperatively, the first dose given immediately after the suturing of the flaps. The rats were anaesthetised on postoperative day 7 to assess the survival of flaps. The difference between the clopidogrel and the control group was significant (P<0.005). The full-thickness skin samples obtained after the calculation of survival percentages revealed thinning of the epidermis layer and active chronic inflammation in both groups. However, diffuse dilated vessels, extravasated eritrocytes were seen in the clopidogrel group flaps. The results indicated a significant increase in flap survival in rats given clopidogrel. Further research is needed to assess the critical doses of clopidogrel to create optimal flap survival improvement.

Effects of Arterial Supercharging and Venous Superdraining Procedures in Skin Flap Survival in Rats

Effects of Arterial Supercharging and Venous Superdraining Procedures in Skin Flap Survival in Rats

Short- and Long-Term Effects of Sildenafil on Skin Flap Survival in Rats

Distal ischemic necrosis of the flap remains an unsolved, challenging problem. Phosphodiesterase (PDE) inhibitors, which include the drug sildenafil, are a relatively new class of U.S. Food and Drug Administration-approved medications whose effect on tissue viability has not been widely explored. The vasodilatory effects of these drugs have the potential to enhance blood flow to flaps and increase their survivability. The purpose of this study was to examine the short- and long-term effects of sildenafil, administered intraperitoneally at a dose of 9 mg/kg per day, on the survival of surgical skin flaps in rats. A McFarlane-type random pattern skin (3 x 10-cm) flap model was used to evaluate the effect of sildenafil on necrosis at multiple time points. Rats were assigned to sildenafil-treated (9 mg/kg per day intraperitoneally; n = 34), vehicle control (n = 35), or sham (no injection; n = 40) groups. In each group, caudally based, dorsal, rectangular (3 x 10-cm) flaps were created. Flap necrosis was determined using orthogonal polarization spectral imaging and digital photography analysis on days 1, 3, 5, and 7 postsurgery. Orthogonal polarization spectral imaging results showed a significant decrease in necrosis and stasis in rats treated with sildenafil on days 1 and 3. Although reductions observed at days 5 and 7 were not as dramatic as days 1 and 3, digital photography analysis confirmed a decrease in the area of necrosis at all time points evaluated. These results suggest that PDE 5 inhibitors may play a more important role in early postoperative skin flap viability rather than at later time points and may be beneficial for skin flap viability as shown in the rat model. PDE 5 inhibitors may reduce the extent of necrosis after reconstructive surgeries.

Enhancement of Dorsal Random-Pattern Skin Flap Survival in Rats With Topical Lidocaine and Prilocaine (EMLA): Enhancement of Flap Survival by EMLA

Enhancement of Dorsal Random-Pattern Skin Flap Survival in Rats With Topical Lidocaine and Prilocaine (EMLA): Enhancement of Flap Survival by EMLA

The Effects of Tumescent Solutions Containing Lidocaine and Epinephrine on Skin Flap Survival in Rats

The Effects of Tumescent Solutions Containing Lidocaine and Epinephrine on Skin Flap Survival in Rats

Effect of caffeic acid phenethyl ester on survival of axial pattern flaps in rats with ischaemia–reperfusion injuries

Oxygen-derived free radicals have been implicated in the pathogenesis of tissue injury after ischaemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis, has been identified as having potent antioxidant and anti-inflammatory properties. We evaluated the ability of CAPE applied intraperitoneally in reducing tissue injury after ischaemia-reperfusion. To investigate whether treatment with CAPE modifies the concentrations of the endogenous indices of oxidant stress, we examined its effects on a model of flap ischaemia-reperfusion injury in rats. CAPE (10 micromol/kg) was given through the peritoneum before reperfusion. CAPE given intraperitoneally had an inhibitory effect on tissue injury after ischaemia-reperfusion comparable to that of a control group. The anti-inflammatory and antioxidant properties of CAPE may contribute to its suppression of tissue injury.

Short and Long Term Effects of Sildenafil on Skin Flap Survival in Rats

(Baur D; Hodam J; Wood LL; Parham M; Keith K; Vazquez R; Ager E; Pizarro J)

Local pharmacological preconditioning increases the survival of experimental skin flaps in rats

Skin flap survival is dependent on an adequate blood supply and on the resistance to ischemia. Experimentally we tested the effect of pharmacological preconditioning on the survival of skin flaps. The survival of an ischemic skin flap (McFarlane flap) was tested using the local application of cobalt gel in three groups of Wistar rats. The mean flap necrosis of the control group was 59.15%. The rats treated by the cobalt gel once a week showed mean necrosis in 39.09%; the rats receiving the application of the cobalt gel three times a week in 26.33%. The treated groups presented with significantly lower flap necrosis in comparison to the untreated controls. There was a significant difference in the flap necrosis occurrence according to the application frequency of the cobalt gel. The expression of the genes involved in angiogenetic processes encoding vascular endothelial growth factor (VEGF) and glycolytic enzymes was influenced in a non-mitochondrial way in this study. The results show that non-mitochondrial preconditioning could prolong the survival of an ischemic flap.

Effects of isoflurane and sevoflurane on the survival of skin flaps in rats

The effects of inhalational anaesthetic agents on survival of flaps are not well known. We investigated the effect of isoflurane and sevoflurane anaesthesia on survival of flaps using a caudally-based McFarlane skin flap in 20 male Wistar rats. Sevoflurane 1 minimum alveolar concentration (MAC) and isoflurane (1 MAC) in oxygen mixture was given to the animals. A 4 x10 cm caudally-based standard McFarlane flap was raised. There were no differences in any haemodynamic values or blood gases between the sevoflurane group and the isoflurane group. Skin flaps were assessed on the seventh day. The isoflurane group had a significantly smaller area of skin flap necrosis and an increased area of flap surviving than the sevoflurane group. We conclude that survival is significantly improved when isoflurane is used as the inhalational anaesthetic rather than sevoflurane.

Effect of short-term use of oral smokeless tobacco on random-pattern skin flap survival in rats

We investigated the effects of smokeless tobacco on the survival of random-pattern skin flaps in rats. Twenty rats were divided into two groups (n=10 each). In the experimental group 200 mg smokeless tobacco (Maras powder) (1 mg nicotine) was inserted intraorally once a day for seven days under general anaesthesia. It was not given to the control group, but the rats were similarly anaesthetised with ketamine. On day 8, plasma cotinine concentrations were measured. The random-pattern dorsal skin flaps measuring 3 x 10 cm were then raised and resutured. Percentage survival area was assessed after a further eight days. The mean (SD) survival was 39 (7)% in the experimental, and 65 (8.9)% in the control, groups (p=0.0001). The mean (SD) plasma cotinine concentrations were 124.4 (73) ng/ml and <10 ng/ml, respectively. Smokeless tobacco use increased the incidence of flap necrosis in random-pattern skin flaps in rats.

Enhancement of dorsal random-pattern skin flap survival in rats with topical lidocaine and prilocaine (EMLA): Enhancement of flap survival by EMLA

Various topical pharmacologic agents have been investigated for their efficacy in preventing or reversing skin flap ischemia. Most of these studies have focused on agents that act on the vascular smooth muscles to cause vasodilatation and improve circulation in the flap. Most of local anesthetics relax vascular smooth muscle and produce peripheral vasodilatation. Topical lidocaine administration was shown that it was an effective and prompt resolution of mechanically induced vasospasm. The topical analgesia cream, EMLA is a mixture of the substances lidocaine and prilocaine. EMLA causes a biphasic vascular response comprising initial blanching and vasoconstriction (maximal after 1.5 h of application) and late erythema and vasodilatation at application times longer than 3 h. To investigate the effect of EMLA on random flap survival, 40 rats were divided in 2 groups of 20 animals. Caudally based random pattern skin flaps were elevated on dorsa of the rats in 10 x 3 cm dimensions. In group 1 which was the treatment group, topical EMLA was applied and covered with Opsite for 1 week whereas in group 2 which was the control group, carrier for EMLA was applied to the flaps. At the end of treatment period, the areas of flap necrosis were measured and percentages of flap survivals were calculated. The mean percentages of flap survivals in group 1 and 2 were 81.2 +/- 1.2 percent and 58.7 +/- 2.3 percent, respectively. Topically administered EMLA might lead to a significant improvement in flap survival. In addition, it is safe, cost-effective, easily applied, and clinically available.

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.

The Effects of Tumescent Solutions Containing Lidocaine and Epinephrine on Skin Flap Survival in Rats

The effects of tumescent solutions consisting of lidocaine and epinephrine on skin flap survival in rats were studied. Dorsal skin flaps of rats were infiltrated using lidocaine (1%) with epinephrine in concentrations of 1:100,000, 1:200,000, 1:400,000, and 1:800,000 prior to elevating flaps of the different experimental groups. The solutions were applied intradermally or subcutaneously, and the flaps were raised "immediately" or "delayed" after injection in the different groups. Control flaps were infiltrated by lidocaine (1%) only. The survival of the flaps was assessed on the seventh day after the operation. As a result, the flaps showed higher necrosis rates in the groups injected by lidocaine with epinephrine in concentration of 1:100,000 and 1:200,000 than of the other experimental or all control groups (P < 0.01). In conclusion, lidocaine with epinephrine in concentrations of 1:400,000 and 1:800,000 was found safe on skin flap survival for tumescent technique in rats.

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.

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.

Efficacy of postoperative steroids on ischemic skin flap survival in rats

Necrosis of skin flaps remains a significant clinical problem. This study examined whether steroids improve skin flap survival in rats. Random skin flaps were raised in 30 male Sprague-Dawley rats. Intramuscular methylprednisolone (n=15) or saline solution (n=15) were administered 1, 24, and 48 h after flap elevation. Surviving flap areas were measured after 7 days. The mean surviving flap area in the methylprednisolone group was greater than that in controls (916 vs. 675 mm). These results suggest that postoperative methylprednisolone improves skin flap viability in the ischemic rat flap model.

Improved dorsal random-pattern skin flap survival in rats with a topically applied combination of nonivamide and nicoboxil.

The effects of a topically applied combination of nonivamide and nicoboxil in improving skin perfusion and preventing distal flap necrosis were tested in a random-pattern dorsal skin flap model. Forty male Wistar rats were randomized into two groups (n = 20), and a standardized dorsal random-pattern skin flap was raised on each rat. Animals in the experimental group were treated with the topically applied drug combination four times per day for 6 days, whereas in the control group only a placebo ointment was applied each time. Skin flap viability was evaluated on day 7, and the extent of skin flap necrosis was compared between the two groups. The topically applied combination of nonivamide and nicoboxil resulted in a statistically significant decrease in skin flap necrosis, compared with the control group (mean percentage of skin flap necrosis in the nonivamide/nicoboxil-treated group, 22.6 +/- 6.0 percent; control group, 36.8 +/- 4.3 percent; p< 0.05). The topical combination of nonivamide and nicoboxil was effective in reducing ischemic necrosis in failing random-pattern skin flaps in this rat model. The results of this study suggest that such a topical drug application might have significant effects in the reduction of ischemic necrosis in the distal parts of skin flaps, and this treatment might also have applications as prophylactic therapy for risky skin flaps.

Adenosine Treatment Augments Random Flap Survival in Rats

Adenosine and purine nucleosides are intermediates in the pathway of purine nucleotide degradation. Adenosine causes vasodilation in all arterioles, except those in the kidney, and is the major regulator of coronary blood flow. The objective of the present study was to investigate the efficacy and role of 9-beta-D-ribofuranosyl adenosine (RFA), a derivative of adenosine, for the augmentation of random flap survival in rats. Varying doses of adenosine and a nonselective adenosine antagonist, 8-phenyltheophylline, were administered before elevation of 3x10 cm dorsal random flaps in 60 rats. The rats were randomly assigned to five groups and received the following treatment: group I (controls) was treated with placebo (saline, 1 mL/day); group II was treated with RFA 25 μg/kg/day; group III was treated with RFA 50 μg/kg/day; group IV was treated with RFA 100 μg/kg/day; and group V was treated with 8-phenyltheophylline (10 mg/kg/day). All daily injections were given intravenously for seven days. Flap survival was assessed on day 8. Therapeutic and higher doses of adenosine-treated flaps showed a significant increase in viability compared with saline-treated flaps in the control group, while there was no improvement in flap survival with low dose adenosine. Phenyltheophylline reversed the beneficial effect of adenosine and increased flap necrosis, which was comparable with that of the controls. The findings show that adenosine can enhance flap survival, and this beneficial effect is possibly due to vasodilation, inhibition of noradrenalin release, reduction of energy consumption, inhibition of reactive oxygen species and a preconditioning effect; however, this effect seems to be dose-related. Adenosine is an easily available drug for clinical use in ischemic heart diseases and should be considered in potentially ischemic flaps.