Faculty Bibliography

The impact of inhibitors of tumor angiogenesis (endostatin, angiostatin) on the neovascularization required for the healing of transferred tissue has not been examined. We investigated the effect of endostatin on the functional neovascularization of random pattern flaps. C57BL6 mice were pretreated with endostatin beginning 3 days prior to surgery (n = 10), and daily injections continued throughout the study. Dorsal random cutaneous flaps were raised in both treatment and control (saline-treated) groups. The remaining cranial attachment was divided on day 9. Oxygen tension (PO2) was measured using a microprobe on days 1, 3, 5 and 16. Flaps were harvested and the vasculature was stained with CD31 on day 16. We found that endostatin significantly decreased flap survival. Mice that were treated with endostatin had fewer CD31+ blood vessels, worse flap perfusion at all time points, and lower oxygen tensions throughout the length of the flap. These findings have potential implications for the patients undergoing antiangiogenesis therapy who require surgical reconstruction

Tissue ischemia remains a common problem in plastic surgery and one for which proangiogenic approaches have been investigated. Given the recent discovery of circulating endothelial stem or progenitor cells that are able to form new blood vessels, the authors sought to determine whether these cells might selectively traffic to regions of tissue ischemia and induce neovascularization. Endothelial progenitor cells were isolated from the peripheral blood of healthy human volunteers and expanded ex vivo for 7 days. Elevation of a cranially based random-pattern skin flap was performed in nude mice, after which they were injected with fluorescent-labeled endothelial progenitor cells (5 x 10(5); n = 15), fluorescent-labeled human microvascular endothelial cells (5 x 10(5); n = 15), or media alone (n = 15). Histologic examination demonstrated that endothelial progenitor cells were recruited to ischemic tissue and first appeared by postoperative day 3. Subsequently, endothelial progenitor cell numbers increased exponentially over time for the remainder of the study [0 cells/mm2 at day 0 (n = 3), 9.6 +/- 0.9 cells/mm2 at day 3 (n = 3), 24.6 +/- 1.5 cells/mm2 at day 7 (n = 3), and 196.3 +/- 9.6 cells/mm2 at day 14 (n = 9)]. At all time points, endothelial progenitor cells localized preferentially to ischemic tissue and healing wound edges, and were not observed in normal, uninjured tissues. Endothelial progenitor cell transplantation led to a statistically significant increase in vascular density in ischemic tissues by postoperative day 14 [28.7 +/- 1.2 in the endothelial progenitor cell group (n = 9) versus 18 +/- 1.1 in the control media group (n = 9) and 17.7 +/- 1.0 in the human microvascular endothelial cell group (n = 9; p < 0.01)]. Endothelial progenitor cell transplantation also showed trends toward increased flap survival [171.2 +/- 18 mm2 in the endothelial progenitor cell group (n = 12) versus 134.2 +/- 10 mm2 in the media group (n = 12) and 145.0 +/- 13 mm2 in the human microvascular endothelial cell group (n = 12)], but this did not reach statistical significance. These findings indicate that local tissue ischemia is a potent stimulus for the recruitment of circulating endothelial progenitor cells. Systemic delivery of endothelial progenitor cells increased neovascularization and suggests that autologous endothelial progenitor cell transplantation may have a role in the salvage of ischemic tissue

Microvascular free-tissue transfer has been a major advance in the treatment of complex traumatic defects of the upper extremity. One hundred and fifty microvascular free-tissue transfers were performed in 133 patients with complex traumatic upper extremity defects at Bellevue Hospital Center from 1976 to 2000. The indication for microvascular free tissue transfers was exposure of vital structure (81 percent), bone defect (11 percent), and functional deficit (8 percent). The parascapular region was the most common donor site used (26 percent). Microvascular free-tissue transfer was performed either emergently at the time of injury (9.3 percent), during days 1 to 5 post injury (19.3 percent), during days 6 to 21 (19.3 percent), or after day 21 (52 percent). The overall flap failure rate was 9 percent. A decreased incidence of flap failure was observed in patients treated from 6 to 21 days post injury (3 percent p<0.05). The most common acute complication was infection at the recipient site, observed in 14 percent of patients overall. A decreased incidence of recipient-site infection was seen in patients who received free flaps at days 6 to 21 (3 percent; p<0.05). In long-term follow-up, the incidences of osteomyelitis and nonunion were lowest in patients treated from 6 to 21 days post injury (0.0 percent and 11 percent, respectively; p<0.05). During the last 10 years, the timing of reconstruction has been altered, and now preferentially microvascular free flaps are performed 6 to 21 days post injury. The treatment algorithm has been simplified and now only four different flaps are used in the majority of patients (70 percent). With this, the authors have witnessed a decrease in failure rates from 11 percent to 4 percent, a decrease in recipient-site infections from 16 percent to 10 percent and a decrease in osteomyelitis from 12 percent to 4 percent. The preferred timing for microvascular free-tissue transfers to the upper extremity is concluded to be 6 to 21 days post injury