Tetrahydropalmatine: Orchestrating survival - Regulating autophagy and apoptosis via the PI3K/AKT/mTOR pathway in perforator flaps.

BACKGROUND: Introduced in clinical practice in 1989, perforator flaps are vital for tissue defect repair, but they are challenged by distal necrosis. Tetrahydropalmatine (THP) from celandine is renowned for its anti-inflammatory and analgesic effects. This study investigates THP's use in perforator flaps. METHODS: Thirty rats were divided into a control group and four THP concentration groups, while seventy-eight rats were categorized as control, THP, THP combined with rapamycin (RAP), and RAP alone. We created 11 cm by 2.5 cm multi-regional perforator flaps on rat backs, assessing survival blood flow and extracting skin flap tissue for autophagy, oxidative stress, apoptosis, and angiogenesis markers. RESULTS: The THP group exhibited significantly reduced distal necrosis, increased blood flow density, and survival area on the seventh day compared to controls. Immunohistochemistry and Western blot results demonstrated improved anti-oxidative stress and angiogenesis markers, along with decreased autophagy and apoptosis indicators. Combining THP with RAP diminished flap survival compared to THP alone. This was supported by protein expression changes in the PI3K-AKT-mTOR pathway. CONCLUSION: THP enhances flap survival by modulating autophagy, reducing tissue edema, promoting angiogenesis, and mitigating apoptosis and oxidative stress. THP offers a potential strategy for enhancing multi-regional perforator flap survival through the PI3K/AKT/mTOR pathway. These findings highlight THP's promise in combatting perforator flap necrosis, uncovering a novel mechanism for its impact on flap survival.

Improvement of multiterritory perforator flap survival supported by a hybrid perfusion mode: A novel strategy and literature review.

Perforator flaps have been widely used in clinical Settings, however, unexpected necrosis was still commonly encountered in the distal portions of multiterritory flaps known as Choke zone III. In this study, we introduced a novel hybrid perfusion technique which is different from the established one of arterial supercharging or venous superdrainage to improve multiterritory flap survival with success. In order to ensure the entire flap survival of multiterritory flaps extending to choke zone III, a "hybrid perfusion" mode by anastomosing a distal vein of the flap with a recipient artery was carried out in two cases based on our previous basic study. In addition, a systematic literature review regarding the established microsurgical assistant techniques of arterial supercharging and venous superdrainage techniques were performed. Both flaps survived uneventfully. At a minimal follow-up of six months, both patients were satisfied with the results. This novel hybrid perfusion technique provides a simple new concept in solving partial necrosis of multiterritory flaps. Further practice is guaranteed for better understanding this unconventional attempt.

Diametric Comparison between the Thoracodorsal Vessel and Deep Inferior Epigastric Vessel in Breast Reconstruction.

BACKGROUND: In microvascular anastomosis, size discrepancy is common and can increase thrombotic complications. If size differences can be predicted, then vessels of the appropriate size can be selected. This study documented the difference in diameter between the thoracodorsal (TD) vessel and deep inferior epigastric perforator (DIEP) pedicle in each patient who underwent breast reconstruction using free tissue transfer. Patients and Methods. This retrospective study included 32 anastomoses (27 breasts including five cases of supercharged anastomosis) of breast reconstruction with the free DIEP flap and TD recipient between August 2018 and June 2019. In the microscopic view, the caliber of the TD vessel, the largest branch to the serratus anterior muscle, the descending branch, the largest and the second largest branches to the latissimus dorsi muscle, and the DIEP pedicle were measured. RESULTS: The diameter of the deep inferior epigastric artery was similar to that of the descending branch, and their anastomosing rate was 56.3%. The diameter of the deep inferior epigastric vein was similar to the branch to the serratus anterior muscle and the descending branch, and their anastomosing rates were 29.3% and 29.3%, respectively. All flaps were survived; however, in one case, a reoperation was needed to remove the hematoma, in which case fat necrosis occurred as the only complication. CONCLUSION: TD branches of similar size to the DIEP pedicle were prioritized in anastomosis. The descending branch and the branch to the serratus anterior muscle are expected to be good candidates as recipients in breast reconstruction with DIEP free flap. Moreover, supercharged anastomosis of DIEP pedicles can be achieved within TD branches.

Visualizing the Pharmacologic Preconditioning Effect of Botulinum Toxin Type A by Infrared Thermography in a Rat Pedicled Perforator Island Flap Model.

BACKGROUND: Surgical delay can improve flap viability, leading to vasodilation, neovascularization, and vessel reorganization. Experiments suggest a similar positive effect of botulinum toxin type A on pedicled flap viability. However, whether it may convert choke anastomoses into true anastomoses and how to identify the optimal timing for flap transfer remain unclear. METHODS: One hundred fifty-four Sprague-Dawley rats were divided into a control group, three saline injection groups, and three botulinum toxin type A injection groups defined by time of injection (2, 3, and 4 weeks before flap harvest). A pedicled 11 × 3-cm flap was marked on the unilateral dorsum of each rat. Before flap harvest, the flap donors were assessed by infrared thermal imaging, postmortem arteriography, immunohistochemical staining of CD31, and enzyme-linked immunosorbent assay. Flap survival area percentage was measured on postoperative day 7. RESULTS: In the control and saline groups, infrared thermography showed three independent white hotspots interspaced by red zones over flaps, whereas it presented a continuous white band in the botulinum toxin type A groups. There was a significant increase in flap survival area, flap surface temperatures, numbers of identifiable vessels in the choke zones, microvascular density, and vascular endothelial growth factor concentration in the botulinum toxin type A groups. CONCLUSIONS: Botulinum toxin type A can convert choke anastomoses into true anastomoses, and its preconditioning effect cannot increase over time; it is appropriate to choose the timing point when the infrared thermal images show a continuous white band existing over flaps for flap transfer.

A New and Innovative Method of Preoperatively Planning and Projecting Vascular Anatomy in DIEP Flap Breast Reconstruction: A Randomized Controlled Trial.

BACKGROUND: In deep inferior epigastric perforator (DIEP) flap breast reconstructions, a free tissue flap from the abdomen is shaped into a breast and transferred to the thorax. Survival of this free flap relies on minuscule blood vessels, so-called perforators, providing blood supply to this newly molded breast. Preoperative mapping of these randomly distributed blood vessels is essential to avoid complications. The purpose of this study was to investigate whether the preoperative projection of a virtual three-dimensional plan based on computed tomographic angiography onto the abdomen leads to more correctly identified perforator locations and less operative time spent on dissecting the free flap compared to the commonly used Doppler ultrasound planning method. METHODS: The authors conducted a randomized, open, single-center, superiority trial in patients undergoing DIEP flap breast reconstruction with 1-week follow-up. Randomized participants were 60 adults (projection method, n = 33; Doppler method, n = 27) undergoing DIEP flap breast reconstruction without lymph node transfer. RESULTS: Sixty patients provided 69 DIEP flaps for analysis. The projection method is capable preoperatively of displaying significantly more perforators compared to the Doppler method (61.7 ± 7.3 percent versus 41.2 ± 8.2 percent, respectively; p = 0.020)). During the procedure, flap harvest time is decreased by 19 minutes (136 ± 7 minutes versus 155 ± 7 minutes; p = 0.012). Complications were comparable across both groups. CONCLUSION: Not only can more perforators be identified intraoperatively using the projection method compared with Doppler ultrasound, there is also a significant time reduction in harvesting the DIEP flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The Skin Bridge Is More Important as an Additional Venous Draining Route in a Perforator-Plus Flap.

BACKGROUND: The skin bridge in the perforator-plus flap is considered as an additional source for arterial input and venous drainage apart from the perforator. However, its exact role requires further elucidation. MATERIALS AND METHODS: Forty rats that underwent flap elevation with a size of 9 × 3 cm on the dorsum were evenly divided into a perforators-intact group with an intact vascular pedicle, an artery-deficient group with the artery ligated, a vein-deficient group with the vein ligated, and a perforators-deficient group with both vessels ligated. The blood perfusion was measured using a laser Doppler flowmeter. On the seventh day, the necrosis rate of the flaps was calculated and the diameter of vessels in the skin bridge was measured. RESULTS: The perfusion pattern was similar between the perforators-intact group and vein-deficient group, as well as between the perforators-deficient group and artery-deficient group. The blood perfusion was much more robust in the perforators-intact and vein-deficient groups. The necrosis rate in the perforators-deficient group (26 ± 1%) was not significantly different from that in the artery-deficient group (29 ± 1%), both of which was significantly larger than that in the perforator-intact (11 ± 3%) and vein-deficient groups (12 ± 4%) (P ˂ 0.001). The venous network of the skin base in the vein-deficient and perforators-deficient groups dilated dramatically, whereas the arterial network in the artery-deficient and perforators-deficient groups had a very modest expansion. CONCLUSIONS: The skin base in a perforator-plus flap is much more important as an additional route for vein drainage than for arterial input.

Bioactive nanoparticle-based formulations increase survival area of perforator flaps in a rat model.

BACKGROUND: Distal flap necrosis is a frequent complication of perforator flaps. Advances in nanotechnology offer exciting new therapeutic approaches. Anti-inflammatory and neo-angiogenic properties of certain metal oxides within the nanoparticles, including bioglass and ceria, may promote flap survival. Here, we explore the ability of various nanoparticle formulations to increase flap survival in a rat model. MATERIALS AND METHODS: A 9 x 3 cm dorsal flap based on the posterior thigh perforator was raised in 32 Lewis rats. They were divided in 4 groups and treated with different nanoparticle suspensions: I-saline (control), II-Bioglass, III-Bioglass/ceria and IV-Zinc-doped strontium-substituted bioglass/ceria. On post-operative day 7, planimetry and laser Doppler analysis were performed to assess flap survival and various samples were collected to investigate angiogenesis, inflammation and toxicity. RESULTS: All nanoparticle-treated groups showed a larger flap survival area as compared to the control group (69.9%), with groups IV (77,3%) and II (76%) achieving statistical significance. Blood flow measurements by laser Doppler analysis showed higher perfusion in the nanoparticle-treated flaps. Tissue analysis revealed higher number of blood vessels and increased VEGF expression in groups II and III. The cytokines CD31 and MCP-1 were decreased in groups II and IV. CONCLUSIONS: Bioglass-based nanoparticles exert local anti-inflammatory and neo-angiogenic effects on the distal part of a perforator flap, increasing therefore its survival. Substitutions in the bioglass matrix and trace metal doping allow for further tuning of regenerative activity. These results showcase the potential utility of these nanoparticles in the clinical setting.

The protective effect of Irisin against ischemia-reperfusion injury after perforator flap grafting in rats.

BACKGROUND: Ischemia-reperfusion injury is one of the reasons for failure of flap grafting. In the present study, we investigated the protective effect of irisin on the survival of perforator flaps in rats. METHODS: A total of 48 adult Sprague-Dawley rats were divided into 2 groups and subjected to vascular clipping of perforator flap. Rats in the experimental group (n = 24) received daily tail intravenous injection of irisin (2 ng/g) for 3 days, while the rest rats in the control group (n = 24) received injection of saline solution of the same dose. On the 7th post-operative day, the surviving area of the flaps were recorded as the percentage of the total flap area. Histology study with haematoxylin and eosin staining were performed in all flaps. Flaps were also evaluated with lead oxide-gelatine-enhanced flap angiography. Immunohistochemical study was performed to evaluate the expression of ErG, a marker of vascular endothelial cells. The tissue of "choke vessels" was excised for quantification of p-Akt/Akt by western blot assay on the 7th post-operative day. RESULTS: On the 7th post-operative day, the percentage of surviving flap area was significantly larger in the rats with irisin administration (experimental group), compared with the control group (P = 0.011). The density of microvessels was significantly higher in the experimental group (P = 0.03) in the histological study and angiography, with a higher expression level of ErG in the immunochemical study (P = 0.01). The p-Akt/Akt was also higher in the experimental group in Western blotting analysis (P < 0.001). CONCLUSION: Irisin has a beneficial effect on protecting perforator flaps from ischemic-reperfusion injury following the flap grafting surgery. It was potentially achieved by promoting proliferation of vascular endothelial cells after flap revascularization. Upregulation of the PI3K/Akt signaling pathway was potentially related with this process.

Reconstruction of a Sacral Pressure Ulcer With an Inferior Gluteal Artery Perforator Flap After Failed Reconstruction Using Bilateral V-Y Advancement Flaps.

Many types of flaps are available if surgical reconstruction of a pressure ulcer is indicated, including a gluteus maximus flap, V-Y advancement flap, and superior gluteal artery perforator flap. Regional flap failure can complicate treatment, requiring additional flap surgery. An 80-year old woman with a 2-year history of being unconscious following a cerebrovascular accident presented with a Stage 4 sacral pressure ulcer of 2 months' duration with eschar and abscess formation. Because the wound measured 15 × 10 cm2, bilateral V-Y advancement flaps were used for surgical closure. However, 1 week later, ischemic change of the wound edges and wound dehiscence were observed. The wound was subsequently closed with an artery perforator (IGAP) flap, an approach that took into consideration religious preference of keeping the body intact. The patient was discharged with a healed wound 6 weeks postoperatively; long-term postoperative surveillance was hindered by the patient's distance from the care facility (she lived on an outlying island). This is the first case report to describe IGAP flap application in a patient with a sacral pressure ulcer after failed reconstruction using bilateral V-Y advancement flaps.

Studying the blood pressures of antegrade and retrograde internal mammary vessels: Do they really work as recipient vessels?

BACKGROUND: The proximal ends of internal mammary (IM) vessels are now the most common recipient vessels for breast reconstruction. On the other hand, bilateral deep inferior epigastric artery perforator (DIEP) flaps are often needed according to the territory and the volume required for reconstruction. The usefulness of retrograde IM vessels as second recipients has recently been reported, but there are very few quantitative studies on the hydrodynamics of the retrograde IM vessels. Because the flow is dependent on the pressure differential, the blood pressures of the antegrade IM artery (AIMA), antegrade IM vein (AIMV), retrograde IM artery (RIMA), retrograde IM vein (RIMV), and recirculated intraflap vein (FV) were investigated to solve this question and to confirm the reliability and usefulness of the retrograde IM vessels. METHODS: Ten free flap breast reconstructions were included in this study. The IM vessels were exposed, and the pressures were measured. After recirculation, the FV pressures were measured when the flap was not ischemic or congestive. Systemic blood pressure was also recorded during the whole measurement period. RESULTS: The AIMA and RIMA pressures were 70.4 ± 8.2 mmHg and 54.0 ± 8.6 mmHg (p = 0.000003), respectively, while the systemic pressure was 65.1 ± 10.0 mmHg. The AIMV pressure was always smaller than the RIMV pressure; the mean AIMV pressure was 5.3 ± 1.6 mmHg. In addition, the FV pressure was greater (p = 0.03) than the RIMV pressure (17.7 ± 9.9 mmHg), while the RIMV pressure was 8.7 ± 2.0 mmHg. CONCLUSIONS: Both the RIMA and RIMV are useful and reliable as second recipients for bipedicled free flap transfers. This is a great benefit because it would provide two recipients in one surgical site and would be especially useful in thin patients or patients with previous abdominal scars requiring double pedicled DIEP flaps. LEVEL OF EVIDENCE: Therapeutic Study, Level IV.

The Concepts of Propeller, Perforator, Keystone, and Other Local Flaps and Their Role in the Evolution of Reconstruction.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand the history and physiology of perforator flaps. 2. Understand the concept of "free-style" perforator flaps and principles in design and harvest. 3. Understand the uses of perforator flaps in reconstruction and applications in new settings. 4. Understand new principles in single and multiple perforator flap harvest and adjunct techniques that can be used in perforator flaps. 5. Highlight pertinent anatomy and techniques for selected perforator flaps described. SUMMARY: Extended knowledge of vascular anatomy has propagated the development of perforator flaps, which preserve muscle function and reduce morbidity. This has been achieved through the exemplary works of Manchot, Salmon, Milton, Taylor, and many others. With over 350 clinically relevant perforators in the body, this has created new flap options and a sense of creative freedom for reconstruction tailored toward a specific defect, without constraints of specific landmarks and using a "free-style" approach. Dominant perforators may be found in zones of high perforator density or "hot spots," which can help to conceptualize local flap options and aid flap design. This article aims to outline the history, physiology, and principles of flap design and harvest, and highlight traditional and evolving concepts and modifications of contemporary and traditional flaps that are changing reconstructive practice. This is a broad overview focusing on clinical applications, highlighting key concepts in a selection of new or evolving flaps being used in clinical practice and providing source references to acquire detailed flap descriptions.

The Effect of Inducible Nitric Oxide Synthase on Multiterritory Perforator Flap Survival in Rats.

Background Inducible nitric oxide synthase (iNOS) plays an important role in vasodilation, angiogenesis, and ischemia-reperfusion injury. We investigated the effects of iNOS on the survival and choke vessels of multiterritory perforator flaps in rats. Methods In this study, 84 rats were divided into two groups of 42 rats each and subjected to multiterritory perforator flap operations. Rats in group A received daily intraperitoneal doses of 100 mg per kg of aminoguanidine (AG) and rats in group B received daily intraperitoneal injections of the same volume of saline solution. On postoperative day 7, the surviving flap area was calculated as a percentage of the total flap dimensions using DP2-BSW software. The diameter and density of microvessels in the second choke zone of the flap were calculated from histology studies. The nitric oxide (NO) content was measured using NO concentration assay kits, and the levels of vascular endothelial growth factor (VEGF) and iNOS were assessed using western blotting. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured using test kits. Laser Doppler imaging was used to evaluate flap perfusion in the second choke zone for 7 days after surgery. Results The flap survival area, diameter and density of microvessels, iNOS and VEGF levels, NO content, blood perfusion, and MDA content were significantly higher in the control group compared with the AG group, whereas SOD activity was significantly lower in the control group. Conclusions iNOS has a beneficial effect on the survival of multiterritory perforator flaps.

Real-time and long-time in vivo imaging in the shortwave infrared window of perforator vessels for more precise evaluation of flap perfusion.

Effective real-time and long-time in vivo imaging for flap perfusion requires bright and stable imaging agents whose emissions can effectively penetrate live tissues without photobleaching. Compared to the standard imaging agent today - intraoperative indocyanine green (ICG), quantum dots (QDs) is a more attractive alternative due to its excellent optical properties including broad emission spectrum and stability against photobleaching. Recent studies have confirmed that the shortwave infrared window (SWIR) between 1000 and 2300 nm is the most sensitive spectral range for in vivo imaging due to its extremely low tissue absorption and autofluorescence. Here, we, for the first time, report a novel approach of flap perfusion assessment that provides real-time and long-time in vivo imaging using lead sulfide (PbS) QDs. Our results show that PbS QDs, as an imaging agent, can improve the stability of in vivo high-resolution images in a sustained manner, thus facilitating the precise evaluation of flap perfusion. In summary, compared to current imaging reporters, SWIR QDs have high photostability and deep tissue penetration, which makes them as promising in vivo imaging agents for more precise evaluation of flap perfusion.

Myosonographic study of abdominal wall dynamics to assess donor site morbidity after microsurgical breast reconstruction with a DIEP or an ms-2 TRAM flap.

BACKGROUND: Currently, autologous breast reconstruction with a free tissue transfer from the lower abdomen is considered to be a safe method that provides a stable long-term solution. The DIEP-flap and the ms-2-TRAM-flap reconstructions have helped reduce donor site morbidity. In order to assess the potential differences between these techniques, we carried out myosonographic evaluations that assessed the muscle dynamics pre- and post-operatively. In addition to investigating the properties of the rectus abdominis muscle post-operatively, this prospective study also allowed us to analyse the muscle preoperatively and to investigate the prospects for harvesting a DIEP-flap as opposed to a TRAM-flap. MATERIALS AND METHODS: Sixty patients underwent breast reconstruction with 71 (11 bilateral) free abdominal wall flaps (DIEP-: n = 48; ms-2-TRAM-flap: n = 23). Myosonographic examinations were performed preoperatively and at 3 and 6 months post-operatively. The thickness of the muscle at relaxation and maximum contraction and the difference between the muscle thickness measured at the two states were measured. A general-linear-model (GLM) was used for statistical analysis. The main variable was the surgical method, and the co-variables included BMI and patient age. The decision on whether to harvest a DIEP- or ms-2-TRAM-flap was made intra-operatively and based on the dominant perforator. RESULTS: It shows that the patients who underwent breast reconstruction with a DIEP-flap had significantly better muscle function (p < 0.05) in the follow-up. In addition, the analysis revealed that better muscle function before surgery made it more likely that a patient would undergo a DIEP-flap-reconstruction successfully. Patient age also had a highly significant effect on muscle recovery (p < 0.0005). CONCLUSIONS: This prospective study used a dynamic ultrasound evaluation of the abdominal wall and showed that the DIEP-flap significantly reduces donor site morbidity compared to the ms-2-TRAM-flap. The study also showed that good preoperative muscle function might increase the probability of surgeons performing a DIEP-flap reconstruction.

Comparison of the effects of different vasoactive and antiplatelet drugs on perforator flap viability. An experimental study.

Perforator flaps are very popular in the reconstruction of soft tissue defects. As these flaps generally depend on a single perforator, drugs that increase the perfusion of the flap and/or prevent vascular complications may increase flap survival. In this study, we compared the effects of systemically administered hydralazine (arterial vasodilator via potassium channels), nifedipine (arterial vasodilator via calcium channels), piracetam (antiplatelet and regulator of microcirculation) and alprostadil (vasodilator, antiplatelet, rheological and cytoprotective) on flap survival in a rat epigastric artery perforator flap model. The percentage of necrosis was measured on each flap and evaluated using one-way analysis of variance (Anova). Histopathological analyses were also performed. Mean flap survival area was 3.85 cm(2) in the control group. Mean flap survival area was 4.88 cm(2) in the nifedipine group, 4.69 cm(2) in the hydralazine group, 10.55 cm(2) in the piracetam group and 11.3 cm(2) in the alprostadil group. When compared with the control group, all drugs except hydralazine improved flap survival; piracetam and alprostadil yielded significantly better results than nifedipine. Only the alprostadil group showed signs of improved vascularity in the histological analysis. As far as perforator flap survival is concerned, drugs that regulate the microcirculation by a combination of different antiaggregation mechanisms appear more beneficial than single action vasodilators. Alprostadil, a synthetic PGE-1 analogue, has combined antiplatelet and vasoactive effects that further increase flap survival.

The Protective Effects of Botulinum Toxin A Against Flap Necrosis After Perforator Twisting and Its Underlying Molecular Mechanism in a Rat Model.

PURPOSE: The purpose of this study was to examine our hypotheses that botulinum toxin A (BoTA) protect necrosis of perforator flap from perforator twisting. METHODS: Twenty-four rats were randomly divided into 2 groups. Twelve International Units of BoTA versus 1.2 mL normal saline was injected subdermally 3 days before flap elevation. In each group, bilateral before deep inferior epigastric perforator (DIEP) flaps, 5 × 3 cm in size, were created. The right and left (180 and 360 degrees of perforator twisting) DIEP flaps were separated. At 1 and 3 days postoperatively, skin above the perforator of the DIEP flaps was harvested to examine the degrees of gene expressions. Final survival percentage of flap and histology were assessed at postoperative day 5. RESULTS: The survival percentage of flap was significantly higher in the BoTA group than in the control group at both DIEP flaps after 180 and 360 degrees of perforator twisting at postoperative day 5 (95.23 ± 2.85% vs 91.00 ± 3.77%; P = 0.021 and 91.59 ± 2.87% vs 30.03 ± 6.91%; P < 0.001, respectively).Higher fibroblast density, enhanced epithelial necrosis, and inflammation were noted in the control group than in the BoTA group. In 180 degrees of perforator twisting group, BoTA may augment angiogenesis possibly via nuclear factor-κB-induced destabilization and the nuclear factor-κB/hypoxia-inducible factor 1-α/vascular endothelial growth factor pathway, whereas in the 360 degrees of perforator twisting group, the mechanistic target of rapamycin/hypoxia-inducible factor 1-α/vascular endothelial growth factor pathway may participate in BoTA-induced effective angiogenesis. CONCLUSIONS: We demonstrated that pretreatment with BoTA protects perforator flap caused by perforator at the pathological and molecular level using an experimental rat model.

Role of the NO/cGMP pathway in postoperative vasodilation in perforator flaps.

BACKGROUND: The nitric oxide (NO)/cyclic guanylyl monophosphate (cGMP) pathway is one of the most important regulators of tissue perfusion. Here, we sought to elucidate the protective effects of the NO/cGMP pathway on the microcirculation of axial pattern skin flaps. MATERIAL AND METHODS: Overall 40 rats were divided into four groups (n = 10 each): group A, sildenafil was administered orally at 10 mg/kg daily; group B, sildenafil citrate (10 mg/kg, oral) and nitro-amino-methyl-L-arginine (L-NAME, intraperitoneal injection), a nitric oxide synthase inhibitor, were administered daily; group C, L-NAME was administered alone; and group D, no drugs were administered. After surgery, the surviving flap area was calculated as a percentage of total flap dimensions using the paper template technique. Angiography and imaging were performed to compare the macrovascular changes of the choke zones in the flaps. Histological examinations were performed to compare the differences in microvascular changes between the two choke zones. RESULTS: A significant improvement of flap survival area and a significant dilation of vessels in both choke zones were found after administration of sildenafil. We also found that the postoperative vasodilation of choke vessels could be altered by inhibition of NO synthase (NOS). Moreover, the vasodilatory effect prolonged by the phosphodiesterase 5 inhibitor sildenafil was attenuated after administration of L-NAME. L-NAME significantly reversed the protection afforded by sildenafil. CONCLUSIONS: Targeting the NO/cGMP pathway can dilate vessels along the axis of the flap, including the choke vessels, thus augmenting flap viability. Therefore, targeting of this pathway may have therapeutic applications.

[Effects of surgical delay procedure on the survival of perforator flap with three angiosomes in rat and lits mechanism].

OBJECTIVE: To observe the effects of surgical delay procedure on the survival of perforator flap with three angiosomes in rat, and to explore its possible mechanism. METHODS: The flap model was a perforator flap with three angiosomes which located on the right dorsal side of a rat based on the right deep circumflex iliac vessel. The two connection areas between the three angiosomes were successively named choke zone (CZ) 1 and CZ 2 beginning from the pedicle to the remote area. A total of 110 SD rats were divided into routine flap group (RF, n = 40), delay only group (DO, n = 30), and delay flap group (DF, n =40) according to the random number table. (1) In group RF, 30 rats were selected according to the random number table, and flap surgery was performed directly. Six rats were sacrificed on post operation day (POD) 0, 1, 2, 3, 7 respectively to collect the full-thickness skin samples at both CZs for HE staining to measure the vascular density and diameter. The rest 10 rats underwent flap surgery immediately after a catheter was successfully implanted into their external jugular vein. A volume of 1.5 mL sodium fluorescein solution (100 g/L) was injected to the 10 rats on POD 0 (5 rats) or POD 1 (5 rats) each time with a 2-day interval to learn the change in flap circulation. Each rat was injected for 4 times. The flap survival rate of the 10 rats was calculated on POD 7, and the configuration and distribution of the vessels in the flap were observed through angiography with the improved perfusion method of lead oxide-gelatin. (2) In group DO, the right thoracodorsal perforators of all the rats were surgically ligated through a small skin incision, and 6 rats were sacrificed on POD 0, 1, 2, 3, 7 respectively. The skin samples of each rat at the same area as in group RF were harvested to measure the vascular density and diameter. (3) In group DF, rats were treated with ligation surgery as in group DO, and then they were assigned and treated as in group RF on POD 7 with corresponding indexes detected later. Data were processed with group t test, analysis of variance with factorial design, and SNK test. RESULTS: (1) Significant differences of vascular density at both CZ 1 and CZ 2 were found on POD 7 among the three groups ( with F values respectively 2. 69 and 2. 76, P values below 0.05). The vascular density values of CZ 1 and CZ 2 of rats in group DF were (29 ± 7) and (31 ± 8) per mm on POD 7, which were significantly higher than those of group RF [(23 ± 5) and (23 ± 3) per mm2, with q values respectively 5.67 and 6.01, P values below 0.05] and those within group DF on POD 0 (with q values respectively 6.42 and 7. 14, P values below 0. 05). On POD 3 and 7, the vascular diameter values of CZ 1 of rats in groups RF and DF were significantly higher than those of group DO (with q values from 8. 15 to 11.13, P values below 0.05). The vascular diameter values of CZ 2 of rats in group DF onPOD 0, 1, 2, 3,7 [(65 ± 8), (63 ± 13), (69 ± 9), (67 ± 8), (64 ± 13) 230m] and in group DO on POD 3 and 7 were significantly higher than those in group RF [respectively (46 ± 10) , (40 ± 9), (43 ± 13), (46 ± 12), (47 ± 11) µm on POD 0, 1,2, 3, 7 ] at corresponding time point (withqval- ues from 7.29 to 10.79, P values below 0.05). The difference in vascular diameter between CZ 1 and CZ 2 was statistically significant in groups RF and DO on POD 3 and 7, and in group DF on POD 0, 1 , and 2 (with q values from 5.32 to 9.56, P values below 0.05). Compared with that on POD 0 within each group, the vascular diameter of CZ 1 in groups RF and DF and that of CZ 2 in group DO increased significantly on POD 3 or 7 (with q values from 6.12 to 8.13, P values below 0.05). (2) In groups DF and RF, blood from the pedicle ran through CZ 1 and covered the dynamic territory successfully within POD 7. On POD 0, the blood within all flaps was blocked for about 3 min after going through CZ 1 at 1 cm distal from CZ 2 in group DF and around CZ 2 in group RF. (3) Flap survival rate of rats in group DF was (95 ± 12) % , which was statistically higher than that of group RF [(80 241 9) % , t = 2.91, P <0.01]. All the partial flap necrosis occurred in potential territory. (4) Compared with the vessels in the left dorsal side without surgery, the vessels of CZ 1 in group RF were dilated obviously, and the boundary between vascular trees became indistinct, but the vessels in CZ 2 changed slightly; the vessels in both CZs in group DF were dilated dramatically. CONCLUSIONS: The delay method could enhance the survival of potential territory in perforator flap with three angiosomes, and it acted mainly by dilating the choke vessels in CZ 2 before flap surgery.

Anatomy and physiology of perforator flaps of the upper limb.

Perforator flaps are an excellent reconstructive option for a functional upper limb reconstruction. This article explores the physiology and general principles of perforator flaps and their indications for use in reconstruction of the upper extremity. Workhorse perforator flaps of the upper extremity, such as the radial artery perforator, ulnar artery perforator, lateral arm perforator, posterior interosseous artery, first dorsal metacarpal artery perforator and perforator-based propeller flaps, are discussed in greater detail.