Vasorelaxation effect and mechanism of action of vascular endothelial growth factor-165 in isolated perfused human skin flaps.

BACKGROUND: Experimental evidence is accumulating to indicate that local acute vascular endothelial growth factor-165 (VEGF(165)) therapy is effective in attenuation of skin ischemia and increase in skin viability in rat skin flap surgery and the mechanism involves vasodilation induced by VEGF(165). So far, the vasodilator effect and mechanism of action of VEGF(165) have not been studied in human skin. The objective of this project is to test the hypothesis that VEGF(165) is also a potent vasodilator in human skin vasculature. MATERIALS AND METHODS: We used an established isolated perfused human skin flap model and pharmacologic probes to demonstrate that VEGF(165) is a potent vasodilator in human skin vasculature and the mechanism involves activation of receptors and postreceptor signaling pathway, which in turn stimulates local synthesis/release of endothelial vasodilators. RESULTS: We observed that VEGF(165) induced a concentration-dependent vasorelaxation in human skin flaps preconstricted with norephinephrine (8 × 10(-7)M; n = 7) or endothelin-1 (3 × 10(-9)M; n = 6). The vasorelaxation potency of VEGF(165) (pD(2) = 12.02 ± 0.25; n = 7) was higher (P < 0.05) than that of acetylcholine (pD(2) = 6.76 ± 0.06; n = 5) in human skin flaps preconstricted with 8 x 10(-7)M of norepinephrine. Using pharmacologic probes, we also detected that the vasorelaxation effect of VEGF(165) in the isolated perfused human skin flaps (n = 4) was triggered by activation of VEGF receptor-2. Furthermore, the postreceptor signaling pathway involved activation of Src family tyrosine kinase, phospholipase C, protein kinase C, an increase in inositol 1,4,5-triphosphate activity, a release of the intracellular Ca(2+) store, and finally synthesis/release of the endothelial nitric oxide (eNO) and prostacyclin and eNO predominantly mediated the vasodilator effect of VEGF(165) in the effector mechanism. CONCLUSION: These findings support our hypothesis that VEGF(165) is a potent vasodilator in human skin vasculature and also provide important insights into the clinical study of local acute VEGF(165) therapy for prevention/treatment of skin ischemia in skin flap surgery.

Abdominoplasty: a comparison of outpatient and inpatient procedures shows that it is a safe and effective procedure for outpatients in an office-based surgery clinic.

BACKGROUND: Abdominoplasty is one of the most commonly performed aesthetic procedures. In our practice, it has recently shifted toward outpatient care as the standard. In this study, the authors investigated the difference in short-term complications in outpatient and inpatient procedures in an office-based surgery clinic. METHODS: A total of 69 consecutive abdominoplasty patients from a plastic surgeon's office-based surgery clinic were reviewed retrospectively. Of these, there were 37 inpatients (mean age at time of operation, 41.2 years; range, 26 to 54 years) and 32 outpatients (mean age at time of operation, 37.5 years; range, 21 to 58 years). Each patient was reviewed for short-term complications, which included wound infection, wound dehiscence, seroma, and/or hematoma. Complications were correlated to inpatient and outpatient groups. RESULTS: Four inpatients (10.8 percent) and one outpatient (3.1 percent) had wound infections, whereas two inpatients (5.4 percent) and two outpatients (6.2 percent) had wound dehiscence/marginal necrosis (a small area of surgical wound opening). The most common perioperative complication was seroma formation, which was seen in seven inpatients (18.9 percent) and eight outpatients (25.0 percent). The overall complication rate in this study was 30.4 percent (29.7 percent in inpatients and 31.2 percent in outpatients). There was no correlation between short-term complications and inpatient/outpatient status. CONCLUSION: These results demonstrate that abdominoplasties can be safely and effectively performed in an outpatient surgery clinic.

Vasodilator effect and mechanism of action of vascular endothelial growth factor in skin vasculature.

Various laboratories have reported that local subcutaneous or subdermal injection of VEGF(165) at the time of surgery effectively attenuated ischemic necrosis in rat skin flaps, but the mechanism was not studied and enhanced angiogenesis was implicated. In the present study, we used the clinically relevant isolated perfused 6 x 16-cm pig buttock skin flap model to 1) test our hypothesis that VEGF(165) is a potent vasodilator and acute VEGF(165) treatment increases skin perfusion; and 2) investigate the mechanism of VEGF(165)-induced skin vasorelaxation. We observed that VEGF(165) (5 x 10(-16)-5 x 10(-11) M) elicited a concentration-dependent decrease in perfusion pressure (i.e., vasorelaxation) in skin flaps preconstricted with a submaximal concentration of norepinephrine (NE), endothelin-1, or U-46619. The VEGF(165)-induced skin vasorelaxation was confirmed using a dermofluorometry technique for assessment of skin perfusion. The vasorelaxation potency of VEGF(165) in NE-preconstricted skin flaps (pD(2) = 13.57 +/- 0.31) was higher (P < 0.05) than that of acetylcholine (pD(2) = 7.08 +/- 0.24). Human placental factor, a specific VEGF receptor-1 agonist, did not elicit any vasorelaxation effect. However, a specific antibody to VEGF receptor-2 (1 microg/ml) or a specific VEGF receptor-2 inhibitor (5 x 10(-6) M SU-1498) blocked the vasorelaxation effect of VEGF(165) in NE-preconstricted skin flaps. These observations indicate that the potent vasorelaxation effect of VEGF(165) in the skin vasculature is initiated by the activation of VEGF receptor-2. Furthermore, using pharmacological probes, we observed that the postreceptor signaling pathways of VEGF(165)-induced skin vasorelaxation involved activation of phospholipase C and protein kinase C, an increase in inositol 1,4,5-trisphosphate activity, release of the intra-cellular Ca(2+) store, and synthesis/release of endothelial nitric oxide, which predominantly triggered the effector mechanism of VEGF(165)-induced vasorelaxation. This information provides, for the first time, an important insight into the mechanism of VEGF(165) protein or gene therapy in the prevention/treatment of ischemia in skin flap surgery and skin ischemic diseases.