Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival.

BACKGROUND: The local skin flap procedure is very useful for reconstruction. However, flap necrosis caused by circulatory failure can occur at its distal portion. Hypoxia-inducible factors (HIFs) in endothelial cells (ECs) help to maintain ECs and promote vascularization, and HIF-2α is abundantly expressed in ECs. However, the mechanisms of action of HIF-2α in ECs are not yet fully understood. The aim of this study was to evaluate the in vivo effects of overexpression of HIF-2α in ECs on skin flap survival. METHODS: A random pattern skin flap (1.0 × 3.0 cm) was elevated on the dorsum of transgenic mice (Tg mice) with EC-specific HIF-2α conditional overexpression and wild-type littermate control mice (n = 6). Flap survival was evaluated on postoperative day 7. Tissue samples from the skin flaps were harvested and analyzed using Western blotting, quantitative reverse transcriptase-polymerase chain reaction, and immunohistochemistry. RESULTS: The HIF-2α mRNA and protein levels were significantly increased in the Tg mice when compared with control mice. Tg mice had significantly increased skin flap survival areas (72.0% ± 2.7%) when compared with wild-type mice (45.7% ± 1.1%). Moreover, histological examination revealed an increase in the subcutaneous blood vessel counts in the Tg mice. CONCLUSIONS: Specific overexpression of HIF-2α in ECs promoted vascularization and enhanced skin flap survival in vivo in a mouse model.

The internal pudendal artery perforator thigh flap: a new freestyle pedicle flap for the ischial region.

BACKGROUND: Recurrence and complication rates of pressure sores are highest in the ischial region, and other donor sites are needed for recurrent pressure sores. The potential of a new freestyle pedicle flap for ischial lesions, an internal pudendal artery perforator (iPap) thigh flap, was examined through anatomical and theoretical analyses and a case series using computed tomography angiography. METHODS: The skin flap was designed in the thigh region based on an iPap. The skin perforators were marked with a Doppler probe. One patient underwent computed tomography angiography with fistulography to identify the damage to or effects on the pedicle vessels of the flap. Debridement of ischial lesions and flap elevation were performed in the jackknife position. RESULTS: The iPap thigh flaps were performed in 5 patients, 4 with ischial pressure sores and 1 with calcinosis cutis of the ischial region. The width and length of the flaps ranged from 5 to 8 cm (mean, 6.6 cm) and 10 to 17 cm (mean, 12.6 cm), respectively. Three patients underwent partial osteotomy of the ischial bone. No complications, including flap necrosis or wound dehiscence of the donor and reconstructed sites, were observed. CONCLUSIONS: The perforator vessels of the internal pudendal artery are very close to the ischial tuberosity. Blood flow to the flap is reliable when careful debridement of the pressure sore is performed. The iPap thigh flap is a new option for soft-tissue defects in the ischial region, including ischial pressure sores.

Risk factors for complications after reconstructive surgery for sternal wound infection.

BACKGROUND: Although the utility of flaps for the treatment of sternal wound infections following median sternotomy has been reported for 30 years, there have been few reports on the risk factors for complications after reconstruction. The objective of this investigation was to identify factors related to complications after the reconstruction of sternal wound infections. METHODS: A retrospective analysis of 74 patients with reconstructive surgery after sternal wound infection over a 5-year period was performed. Clinical data including age, sex, body mass index (BMI), comorbidities, bacterial culture, previous cardiac surgery, wound depth, mortality rate, type of reconstructive procedure, and complication rate were collected. RESULTS: The patients' BMI ranged from 15.2 to 33.6 kg/m(2) (mean, 23.1±3.74 kg/m(2)). Wound closure complications after reconstructive surgery were observed in 36.5% of the cases. The mortality rate was 2.7%. Diabetes mellitus significantly affected the rate of wound closure complications (P=0.041). A significant difference in the number of complications was seen between Staphylococcus aureus (S. aureus) and coagulase-negative Staphylococci (P=0.011). There was a correlation between harvesting of the internal thoracic artery and postoperative complications (P=0.048). The complication rates of the pectoralis major flap, rectus abdominis flap, omentum flap, a combination of pectoralis major flap and rectus abdominis flap, and direct closure were 23.3%, 33.3%, 100%, 37.5%, and 35.7%, respectively. CONCLUSIONS: Diabetes mellitus, S. aureus, harvesting of the internal thoracic artery, and omentum flap were significant factors for complications after reconstruction. The omentum flap volume may be related to the complications associated with the omentum flap transfer in the present study.

Systemic preconditioning by a prolyl hydroxylase inhibitor promotes prevention of skin flap necrosis via HIF-1-induced bone marrow-derived cells.

BACKGROUND: Local skin flaps often present with flap necrosis caused by critical disruption of the blood supply. Although animal studies demonstrate enhanced angiogenesis in ischemic tissue, no strategy for clinical application of this phenomenon has yet been defined. Hypoxia-inducible factor 1 (HIF-1) plays a pivotal role in ischemic vascular responses, and its expression is induced by the prolyl hydroxylase inhibitor dimethyloxalylglycine (DMOG). We assessed whether preoperative stabilization of HIF-1 by systemic introduction of DMOG improves skin flap survival. METHODS AND RESULTS: Mice with ischemic skin flaps on the dorsum were treated intraperitoneally with DMOG 48 hr prior to surgery. The surviving area with neovascularization of the ischemic flaps was significantly greater in the DMOG-treated mice. Significantly fewer apoptotic cells were present in the ischemic flaps of DMOG-treated mice. Interestingly, marked increases in circulating endothelial progenitor cells (EPCs) and bone marrow proliferative progenitor cells were observed within 48 hr after DMOG treatment. Furthermore, heterozygous HIF-1α-deficient mice exhibited smaller surviving flap areas, fewer circulating EPCs, and larger numbers of apoptotic cells than did wild-type mice, while DMOG pretreatment of the mutant mice completely restored these parameters. Finally, reconstitution of wild-type mice with the heterozygous deficient bone marrow cells significantly decreased skin flap survival. CONCLUSION: We demonstrated that transient activation of the HIF signaling pathway by a single systemic DMOG treatment upregulates not only anti-apoptotic pathways but also enhances neovascularization with concomitant increase in the numbers of bone marrow-derived progenitor cells.

Calcifying aponeurotic fibroma of the elbow: a case report.

Calcifying aponeurotic fibroma is a rare soft tissue tumor that typically occurs in the distal extremities of children and adolescents. Because a calcifying aponeurotic fibroma is an ill-defined mass and has a tendency to infiltrate the surrounding tissue, local recurrence rates are 50%. We report a case of calcifying aponeurotic fibroma occurring in the elbow region, an uncommon site. The patient is followed up for 6 years without local recurrence of the tumor.