Effects of combined natural hirudin and hyperbaric oxygen therapy on survival of transplanted random-pattern skin flap in rats / 中国修复重建外科杂志

Objective: To investigate the effect of natural hirudin combined with hyperbaric oxygen therapy on the survival of transplanted random-pattern skin flap in rats.

Clinical Cases Analysis of Forearm Free Fasciocutaneous Flaps on Oral Cavity Defect Area

The Usefulness of Transcutaneous Tissue Oxygen Pressure (TcpO2) for Determination of the Point of Time at Venous Revascularization

PURPOSE: The purpose of this study is to delineate the optimal time of venous revascularization for preventing the flap necrosis due to venous occlusion, and to clarify the usefulness of tissue oxygen pressure (TcpO2) in the determination of the point of time for venous revascularization. METHODS: Thirty-six, 3 x 3 cm sized epigastric island flap was elevated in left abdomen of male Sprague-Dawley rat weighing 250 gram. Flaps were randomly assigned to six groups of six flaps according to the duration of venous occlusion with microvascular clamp; 10 minutes in the group I as the control, 60 minutes in the group II, 2 hours in the group III, 3 hours in the group IV, 4 hours in the group V, and 6 hours in the group VI, respectively. Just before removal of clamp after flap was reposed in situ, the ratio of TcpO2 (tissue oxygen pressure) of the island flap to that of right abdomen was calculated in each group, and tissue specimen was harvested from the distal area of the flap for histological evaluation of vascular change. Five days later, survival area of the flap was estimated, and evaluated the correlation between the tissue oxygen pressure and the rate of flap survival. RESULTS: The TcpO2 and the survival rate of flap were decreased proportionally with the duration of venous occlusion. The ratio of the TcpO2 of the flap is decreased abruptly to below sixty percentile compared to the TcpO2 of normal tissue, and the survived area of the flap is decreased to nine-tenth of the designed size after three hours of total venous occlusion. Histologically, the number of congested vessels was increased according to venous occluded time, and proportionally increased after 3-hours of occlusion significantly. CONCLUSION: There is a close correlation between the TcpO2 and the survival rate of flaps according to the duration of venous occlusion. Therefore, the TcpO2 represents the hemodynamic changes within the flap, and thought to be an alternative effective tool in the flap monitoring for venous revascularization.

The Effect of Botulinum Toxin-A on the Survival of Random-Pattern Cutaneous Flap in Rat

PURPOSE: Botulinum toxin type A(BoTA) can block the release of vasoconstriction cotransmitters as well as acetylcholine in nerve terminal. The authors observed that BoTA increases flap survival by preventing sympathetic collapse of peripheral vessels. METHODS: 10 Sprague Dawley rats were divided into control(n=5), and BoTA group(n=5). 3x10cm sized random pattern cutaneous flaps were elevated on the dorsal side in both groups. In BoTA group, BoTA was injected into the flap via intradermal to subdermal route, 7 days before the flap elevation. Flap survival rates (survival area/total area) were measured 7 days after the elevation. Cutaneous blood flow was measured in proximal, middle and distal compartments of the flap using laser Doppler flowmetry initially, preoperatively, at immediate postoperation, and 7 days after flap elevation, respectively. Histological examination was performed 7 days after the flap elevation. The number and shape of the vessels were evaluated under microscope. RESULTS: Mean flap survival was 53.18+/-6.58% in control group and 93.79+/-6.06% in BoTA group, displaying statistically significant difference(p=0.0008, p< 0.05). In the control group, blood flow to the middle and distal compartments of the flap decreased significantly immediately after flap elevation. In the BoTA group, blood flow to the middle compartment did not decrease(p=0.002) and slightly decreased in the distal compartment(p=0.001). Cutaneous blood flow was significantly higher in all compartments of the flap in BoTA group than in control group, 7 days after the flap elevation. In histopathologic examination, greater number of vessels were noted in the BoTA group than in the control group. CONCLUSION: Botulinum toxin A can increase the survival of the random pattern cutaneous flap in rats by preventing the sympathetic collapse of peripheral vessels.

The Effect of Melatonin on the Random Flap Survival in the Rat

PURPOSE: In skin flap surgery, surgeons often encounter distal ischemia of the flap. If a powerful free radical scavenger is used, it may reduce the formation of free radical and improves the survival of flap. Thus, the present study purposed to examine whether the survival of flap can be enhanced by administering melatonin, which is known to be a powerful free radical scavenger a antioxidant molecule. METHODS: We divided 40 Sprague-Dawley rats into 4 groups, 10 in each group. For the control group(n=10), we intraperitoneally injected only carrier solution once 30 minutes before the operation, and once a day for 7 days from the day of operation. Among the experimental groups, a group(n=10) was administered with dimethyl sulfoxide(DMSO), in another group(n=10), melatonin was intraperitoneally injected, and in the other(n=10) melatonin was intraperitoneally injected and applied topically(2cc of 1% melatonin) to the operation site. Caudally based skin flaps measuring 3x10cm2 were elevated on the mid-dorsum of the rats. and then repositioned. On the seventh postoperative day, the survival area of the flap was measured and tissues were examined under the light microscope. RESULTS: The control group, the DMSO group, the melatonin administration group and the melatonin administration and application group showed the mean survival rates of 55.26+/-9.2%, 70.29+/-7.47%, 81.45+/-4.14% and 86.1+/-1.52%, respectively, for 30cm2 of flap. Compared to the control group, the experimental groups showed a significantly high increase in survival area at significance level of 95%. CONCLUSION: In this study, the survival rate of flap was enhanced through the administration of melatonin after flap surgery. This suggests that melatonin not only functions as a powerful free radical scavenger and oxygen radical scavenger but also stabilizes and protects cells, and by doing so, enhances the survival of moderately injured ischemic sites in the distal end of flap.

The Effect of Erythropoietin on Ischemia-Reperfusion Injury: An Experimental Study in Rat TRAM Flap Model

PURPOSE: Erythropoietin is traditionally known to regulate erythropoiesis, but recently its protective effect against ischemia-reperfusion injury has been studied mainly in cardiovascular and neuronal systems. This study was planned to investigate the effects of recombinant human erythropoietin on ischemia-reperfusion injury in rat TRAM flap model. METHODS: Superiorly based TRAM flap was elevated and ischemic insult was given for four hours. Thirty minutes before reperfusion, single dose recombinant human Erythropoietin(5000IU/kg) was injected via intraperitoneal route in the treatment group. At 24 hours postoperatively, systemic neutrophil count, tissue myeloperoxidase activity, malonyldialdehyde amount, nitric oxide content, tissue water content and histologic finding of inflammation was evaluated. On 10 days postoperatively, flap survival rate, angiogenesis and change in hematocrit level was evaluated. RESULTS: Tissue nitric oxide level was significantly higher and myeloperoxidase activity was significantly lower in the treatment group 24 hours after reperfusion. Tissue water content was significantly lower in the treatment group. Perivascular neutrophil infiltration and intravascular adhesion was marked in the control group. Mean flap survival after ten days was 69% in the treatment group, and 47% in the control group, demonstrating a significant difference. Neovascularization in the treatment group also outnumbered the control group. No significant hematocrit rise was noted ten days after erythropoietin administration. CONCLUSION: Recombinant human Erythropoietin improved flap survival in ischemia-reperfusion injured rat TRAM flaps, at least partially owing to suppressed inflammation, increased nitric oxide, and enhanced angiogenesis.

An Effects of a New PGE1: Lipo-AS013 on Blood Flow and Survival of Skin Flap

Prostaglandin E1(PGE1) is known to have various physiological action such as vasodilatation, decrease of blood pressure, angiogenesis, inhibition of platelet aggregation and so forth. PGE1 has been developed in many different formulations in order to overcome its chemical instability and deactivation in the lungs when administered parenterally. Lipo-AS013 is a potent drug with higher chemical stability and greater vascular wall targeting than others. The study was done on 3x10 cm model flap of dorsal skin of Sprague-Dawley rats and the flap perfusion survival were observed and documented. The flap treated with Lipo-AS013 beforehand was given intravenously Sodium fluorescein 10 minutes later, and then Percent Dye Fluorescence Index(% DFI) was calculated. The results were compared to a control group and the group administered locally epinephrine. In the control group, the % DFI and flap survival rate increased from 54.1+/-6.7 to 65.0+/-2.6(p<0.01) while in Lipo-AS013 group from 55.3+/-2.2 to 67.4+/-1.9(p<0.01), respectively. In the epinephrine group, the % DFI(p<0.05) and flap survival rate(p<0.001) decreased. In the both epinephrine and Lipo-AS013 group Percent DFI and flap survival rate are comparable with the control group. The result indicates that the potent Lipo-AS013 enhances the blood flow and flap survival. This highly potent Lipo-AS013 may have targeting ability and accumulate PGE1 onto the vascular walls. A quantitative analysis of fluorescence on the skin surface is a reliable tool to measure the blood perfusion into an ischemic flap and its viability. Further comparative study with conventional PGE1 and Lipo-PGE1 is needed in order to clarify the action and efficiency of Lipo-AS013.

Effect of induction chemotherapy on flap survival rate in microsurgery

PURPOSE: Neoadjuvant chemotherapy is commonly used to treat cancer patients as adjunct treatment, but if the microvascular tissue transfer is performed simulataneously with cancer resection surgery, the induction chemotherapy might affect the survival rate of vascularized free flap. Our study will focus on the effect of induction chemotherapy on the free flaps which were made on white rat abdomen after injection of 5-FU. MATERIALS AND METHODS: The experimental rat groups were divided into three groups (total 24 rats) as a normal control group, 24 hrs group after 5-FU injection, 3 days group after 5-FU injection. Inferior abdominal island flaps of 8 Sprague Dawley rats on each group were made and immediately were induced into an ischemic state by clamping the supplying inferior epigastric artery and vein with microvascular clamp for a hour to induce a similiar free flap circumstance, then the inferior abdominal skin flaps were reperfused by releasing the clamps. The flaps on abdomen were repositioned and sutured. The experimental data for flap survival rate was collected by digital photo taking, analysed by computer image program to compare with the flap luminosity. The rats were sacrificed at 3 days, 5 days, 7 days after flap preparation and specimens of the flap were taken and stained with H-E staining. The microscopic finding was made under magnification of 200 and 400. RESULTS: 1. Gross findings on each groups showed the healing condition was good as following sequences; normal, 24 hrs group after chemotherapy, 3 days group after chemotherpy. 2. The values of flap luminosity for evaluation of flap survival rate also showed the same sequences as gross findings of healing state. 3. The microscopic findings of epidermis necrosis, inflammation state, dermis fibrosis, vessel change, fatty tissue layer thinning were compared with each group. The 3 days group after chemotherapy showed remarkably poor healing condition compared to other groups. CONCULSION: Chemotherapy agents affected the healing process of free flap, but healing condition was recovered spontaneously as post-injection periods passed out. In opposite to our expectation, 3 days group showed the bad flap condition in comparing with 24 hours group which was considered as immatured body circulation state of chemotherapy agent. It showed that 3 weeks in human being after chemotherapy was not proper as timing of microvascular tissue transfer if 3 days group in rat was considered as same healing period of 3 weeks in human being. More delayed healing timing than 3 weeks might be required in clinical application of free tissue transfer.

Estimation of Lower Abdominal Flap Survival in Rabbit Model Using Laser Doppler Flowmetry Value

Microsurgery has developed over the last three decades to become a routine surgical operation and it's indications for autogenous tissue transplant have been increased. Despite of initial success rate ranging from 80 to 95 percent, the compromise of vascular pedicle causing flap loss has been still one of the serious complications in the microsurgery. As the success of re-exploration is inversely proportional to the time elapsed till the clinical recognition of vascular complication after operation, early detection of perfusion compromise is an important determinant of flap salvage. In this sense, the laser doppler flowmetry has been widely used as an objective monitoring system for the flap survival. This study was designed to investigate the critical time point of flap survival and to estimate the variation of flow value measured by laser doppler flowmetry. Sixteen New Zealand white rabbits weighed from 1.5 kg to 2 kg were used. The lower abdominal island flap(10 5 cm) based on the superficial epigastric pedicle was elevated and repositioned again. The flow values were checked before the flap elevation, immediately after the flap elevation. And thereafter, they were also checked before and after the ligation of pedicle at the 6th, 8th, 10th, 12th, 14th and 16th day of experimental period. After a preliminary study, additional 5 rabbits on each 14th and 16th experimental day were included in the same experimental procedure. The LD value in each point was measured with the laser doppler flowmetry and it was taken as the value of LD at the experimental time. After that, LD ratio(D/C) was obtained by calculating the ratio of LD value(D) after pedicle ligation to that(C) before pedicle ligation in each experimental period. The flap necrosis was noted from the 6th postoperative day to the 12th postoperative day after the pedicle ligation. On the 14th day after the operation, flap survival was noticed after the pedicle ligation. In the group of flap necrosis, LD ratio(D/C) from the 6th day to the 12th postoperativ

Effect of Vitamin C on the Random Flap Survival in the Rat

Vitamin C acts as a antioxidants and as free radical scavengers in biological systems. The objective of this study was to examine whether the administration of vitamin C could improve the skin flap survival. Sprague-Dawley rats (n = 40) were divided into 4 groups (n = 10); normal saline, vitamin C 200 mg/day, vitamin C 500 mg/day, vitamin C 1000 mg/day were injected subcutaneously to each group (n = 10). A classic caudally based random flap (2 X 7 cm) was elevated on the dorsum of rats and then sutured to its normal position. On the 3rd, 7th, 14th days postoperatively each animal was evaluated for percentage area of flap survival by paper template technique, thereafter rats were sacrificed and we obtained tissue from the distal ends of the flap. Following is our results. 1) The experimental group treated with vitamin C revealed an increased rate of random pattern skin flap survival compared with the control group (p < 0.005). 2) There was correlation of vitamin C dosage with flap survival rate (Spearman's correlation coefficient = 0.971). 3) The biopsy of the control group showed extensive atrophy and necrosis. However, New capillary proliferation and collagen deposition were noted in the vitamin C 200 mg and 500mg treated group. In the vitamin 1000 mg group, microscopic findings were very alike compared with normal rat skin texture. Finally, we concluded that the Vitamin C supplement increases survival rate of random pattern flap in rat skin flap model, and flap survival is correlated with vitamin C dosage.

The Effect of Topical Application of Capsaicin on the Flap Survival

Capsaicin is the principal pungent component of Capsicum fruits. Biological effect of capsaicin is various and complicated. This study was undertaken to define the effect of topical application of capsaicin on flap survival in rat. Fourty Sprague Dawley rats were divided into four groups. With ten rats in each group, group A was only flap elevation group, as the control, group B was applied 0.025% capsaicin ointment for 7 days after skin flap elevation, group C was applied 0.075% capsaicin ointment for 7 days after skin flap elevation, group D was elevated two skin flap and one flap was control, the other flap was applied 0.075% capsaicin ointment for 7 days. Group A demonstrate 46.2+ 2.5% flap survival rate. Group B demonstrate 48.8+/-7.8% of flap survival rate, group C demonstrate 53.3+/-7.0% of flap survival rate. Control flap on group D demonstrate 43.5+/-3.5% of flap survival rate, 0.075% capsaicin applied flap demonstrate 52.9+/-7.2% of flap survival rate. Compared to the control group, increase in survival rate in group B was not statistically significant. The mean flap survival rate in group C was significantly increased than control group (p < 0.05). Compared to the control flap in group D, 0.075% capsaicin applied flap showed significantly higher flap survival rate. Based upon this data, local application of 0.075% capsaicin ointment demonstrate significantly increased value of survival area and survival rate on skin flap in rat (p < 0.05). And further studies may be needed for the evaluation of correct action mechanisms of capsaicin.

The Advantage of the Skin Flap Survival Effected by Moxibustion Stimulation / 日本東洋医学雑誌

Augmentation of skin flap survival remains one of the principle concerns in the field of reconstructive plastic surgery. Moxibustion was thought to have potential in this area because it is known to induce proliferation of the blood capillaries of the skin. The authors therefore investigated the effects of moxibustion on skin flap survival in rats.<br>Male Wistar rats of about 200g were divided into four groups: Group I was stimulated before the operation, II after the operation, III both before and after the operation and Group IV served as an unstimulated control. Ten spots were selected for five days of stimulation with moxibustion (Kamayamini) on the skin flap, however, no stimulation was given the day before or the day of the operation. The caudal skin flap (9cm×3cm) was made under pentobarbital anesthesia (intraperitoneal; 26m<i>l</i>/kg).<br>A significant increase in the survival area in Groups I and II when compared with Group IV. It was therefore concluded that stimulation with moxibustion may be a valuable method of improving skin flap survival. For clinical application, further improvements such as exclusion of scar formation may be necessary.