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: BackgroundRecent studies have shown that platelets play an important role in the pathogenesis of reperfusion injury. Using an inferior epigastric artery skin flap as a flap ischemia/reperfusion (I/R) injury model, we investigated whether the administration of a nitric oxide (NO) donor, nitrosoglutathione (GSNO), could decrease platelet activation and modulate the NO synthase (NOS) activity of platelets and promote flap survival.: MethodsThirty minutes before flap reperfusion, normal saline (1 mL), nitrosoglutathione (GSNO 0.2, 0.6, 3 mg/kg), or NG-nitro-l-arginine-methyl ester (450 mg/kg) was injected intravenously in 10 rats, respectively. The p-selectin (CD62P) expression of platelet activation was detected by a flow cytometry. Immunohistochemical staining was performed to investigate the CD62P deposition on the microvasculature of the flap vessels. NOS isoform expression in the platelets was evaluated by Western blot. Tissue perfusion was monitored by using laser-Doppler flowmetry. Survival areas were assessed at 7 days postoperatively: ResultsAn optimal dose of GSNO (0.6 mg/kg), significantly decreased in CD62P expression on platelets (P < 0.001) and its deposition on the flap vessels, selectively suppressed iNOS induction of platelet, and significantly improved blood perfusion and the flap survival rate (59.8 ± 4.9% versus 22.1 ± 6.1%, P < 0.001). In contrast, the NO synthase inhibitor, NG-nitro-l-arginine methyl ester, although inhibiting iNOS expression of platelets, compromised platelet activation, tissue perfusion, and flap survival.: ConclusionThis study suggests that GSNO can appropriately donate NO to suppress platelet activation and platelet iNOS induction, resulting in less platelet activation, better blood perfusion, and flap survival after I/R injury. [Copyright &y& Elsevier]

Background. Evidence has shown that platelets play an important role in the pathogenesis of flap failure. Employing a rat inferior epigastric artery skin flap as a flap reperfusion injury model, we investigated whether platelet activation was involved in the skin flap failure and whether administration of abciximab (ReoPro, chimeric 7E3 Fab) could decrease platelet activation/aggregation and promote flap survival.Methods. Normal saline and abciximab (0.06 mg/kg; 0.2 mg/kg; 1 mg/kg) were injected intravenously into skin flaps 30 min before reperfusion and 1 h after reperfusion (each subgroup n = 6). Platelet activation as demonstrated by P-selectin (CD62P) was analyzed by flow cytometry. P-selectin expression on flap vessels was detected by immunohistochemical staining. Platelet aggregation was induced with adenosine diphosphate (ADP). Laser Doppler flowmetry monitored tissue perfusion. The surviving area was evaluated 7 days postoperatively.Results. CD62P progressively increased after reperfusion. The peak CD62P occurred after reperfusion for 12 h. Immunohistochemical staining showed CD62P significantly deposited on the endothelium after reperfusion. Administration of abciximab (1 mg/kg) effectively improved flap survival rate (P = 0.003), significantly decreased ADP-induced platelet aggregation (P < 0.001), and suppressed CD62P expression on blood platelets (P = 0.002) and its deposition on the flap vessels.Conclusion. Abciximab promotion of skin flap survival is due to blocked platelet activation/aggregation and decreased activated-platelet deposition on the vascular endothelium. Thus, administration of a platelet glycoprotein IIb/IIIa receptor antagonist such as abciximab may save the skin flap from reperfusion injury after a long period of ischemia. [Copyright &y& Elsevier]

Objective: Strong vascular endothelial growth factor (VEGF) expression of osteoprogenitors was found in callus site during fracture healing. The aim of this study was to investigate whether VEGF modulates the angiogenesis and osteogenesis in shockwave-promoted fracture healing in rabbits. Materials and Methods: Twenty-seven Japanese rabbits were used in the study. A fracture of left tibia with 5 mm gap was created, and the fracture was stabilized with an external fixator. The rabbits were randomly divided into three groups. Group I was the control group and received no shockwave therapy. Group II received shockwave therapy, and group III was pretreated with bevacizumab, a monoclonal antibody against VEGF, before receiving shockwave. Radiographs of the tibia were obtained at 1, 4, and 8 wk. Bone mineral density was performed at 8 wk. The rabbits were euthanized at 8 wk, and the bone specimens were subjected to histomorphological examination and immunohistochemical analysis. Results: At 8 wk, radiographs showed considerably better bone healing and remodeling of the fracture in group II compared with groups I and III, whereas no discernable difference was noted between group I and group III. The BMD values were significantly higher in group II than groups I and III, but no difference noted between group I and group III. In histomorphological examination, significant increases in bone tissue was were noted in group II compared with groups I and III, but no difference was noted between group I and group III. In immunohistochemical analysis, significant increases in VEGF, vWF, PCNA, BMP-2 and osteocalcin, and a decrease in TUNEL expression were observed in group II compared with groups I and III, but no statistical difference was noted between group I and group III. Conclusion: Significant increases in VEGF and angiogenic and osteogenic growth factors were noted in shockwave-promoted bone healing. Pre-treatment with bevacizumab inhibited VEGF and in turn, attenuated the effect of shockwave. It appears that VEGF modulates angiogenesis and osteogenesis in shockwave-promoted bone healing in rabbits. [Copyright &y& Elsevier]

Background: This prospective study compared extracorporeal shockwave treatment (ESWT) with hyperbaric oxygen therapy (HBO) in chronic diabetic foot ulcers. Patients and methods: Seventy-two patients with 72 chronic diabetic foot ulcers were randomly divided into two groups of similar demographics with 34 patients with 36 ulcers in the ESWT group and 36 patients with 36 ulcers in the HBO group. Patients in the ESWT group received 300 + 100/cm2 impulses of shockwave at 0.11 mJ/cm2 energy flux density every 2 wk for 6 wk, whereas patients in the HBO group received HBO daily for 20 treatments. The evaluations included clinical assessment of the ulcers with photo-documentation, blood flow perfusion scan, bacteriological examination, histological study, and immunohistochemical analysis. Results: The overall results showed completely healed in 31%, improved in 58%, and unchanged in 11% for the ESWT group and 22% completely healed, 50% improved, and 28% unchanged for the HBO group. The ESWT group showed significantly better clinical results and local blood flow perfusion, higher cell concentration, and activity than the HBO group. On immunohistochemical analysis, the ESWT group demonstrated significant increases in endothelial nitric oxide synthase, vessel endothelial growth factor, and proliferation cell nuclear antigen expressions and a decrease in transference-mediated digoxigenin-deoxy-UTP nick end-labeling expression than the HBO group. Conclusions: ESWT appears to be more effective than HBO in chronic diabetic foot ulcers. [Copyright &y& Elsevier]

Objective: Distal skin flap ischemic necrosis is a significant challenge in reconstructive surgery. This study assessed whether extracorporeal shock wave (ESW) treatment rescues compromised flap tissue by enhancing tissue perfusion and is associated with suppression of inflammatory response. Methods: This study used the dorsal skin random flap model in a rodent. Thirty-six male Sprague Dawley rats were divided into three groups. Group I, a control group, received no treatment. Group II was administrated 500 impulses of ESW treatment at 0.15 mJ/mm2 as a single treatment immediately postoperatively. Group III received 500 impulses of ESW at 0.15 mJ/mm2 applied immediately postoperatively and the day following surgery. Flap blood perfusion was detected by laser Doppler. Flap survival/necrosis area and histological staining of flap ischemia zone was performed on day 7 postoperatively. The tumor necrosis factor alpha, vascular endothelial growth factor, and proliferating cell nuclear antigen expression were evaluated with immunohistochemical staining. Results: Experimental results indicated that the necrotic area of the flaps in Group II was significantly reduced compared with that in the control group (13 ± 2.6% versus 42 ± 5.7%, P < 0.01). There was small and insignificant reduction in the necrotic area in Group III compared with the controls. Flap tissue blood perfusion was significantly increased postoperatively in Group II. Histological staining indicated that ESW treatment substantially increased vascular endothelial growth factor and proliferating cell nuclear antigen expressions, reduced leukocyte infiltration, and suppression of tumor necrosis factor alpha expression in flap tissue ischemic zones in Group II compared with that in controls. Conclusion: Optimal dosage of ESW treatment has a positive effect in rescuing ischemic zone of flap by increasing tissue perfusion and is associated with suppressing inflammatory response. [Copyright &y& Elsevier]