Abstract-Techniques of arterial injury commonly used in animals to mimic endovascular procedures are not suitable for small mouse arteries. This has limited examination of the response to arterial injury in genetically modified mice. We therefore sought to develop a model of transluminal injury to the mouse femoral artery that would be reproducible and result in substantial levels of intimal hyperplasia. Mice of the C57BL/6 strain underwent bilateral femoral artery denudation by passage of an angioplasty guidewire. Intimal hyperplasia was observed in 10% of injured arteries at 1 week, in 88% at 2 weeks, and in 90% at 4 weeks. The mean intimal-to-medial area ratio reached 1.1Ϯ0.1 at 4 weeks. No intimal proliferation was found in control sham-operated arteries. One hour after injury, the denuded surface was covered with platelets and leukocytes, predominantly neutrophils. This was associated with the accumulation of P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. Expression of these adhesion molecules was not seen in the underlying medial smooth muscle cells. At 24 hours, few neutrophils remained on the denuded surface. At 1 week, macrophages and platelets were present in the vessel wall, partially covered by regenerated endothelium. Transluminal wire injury to the mouse femoral artery induces abundant intimal hyperplasia formation by 2 and 4 weeks and elicits the rapid accumulation of leukocytes and adhesion molecules on the denuded luminal surface. This model will be a valuable tool to study arterial injury in genetically modified mouse models.

Microvascular surgery has emerged as an attractive area for recent advances in the field of gene therapy. The present study investigated the survival of ischemic, experimental skin flaps after treatment with the gene encoding vascular endothelial growth factor (VEGF). In 30 Sprague-Dawley rats, anterior abdominal skin flaps supplied by the epigastric artery and vein were created. Ten animals were treated with a mixture of liposomes and the cDNA encoding the 121-amino acid isoform of VEGF. Another 10 animals were treated with control plasmid DNA and liposome transfection medium; a third group of 10 animals was given physiologic saline. Each solution was injected directly into the femoral artery distal to the origin of the epigastric pedicle supplying the flap. Four days after injection, the pedicle was ligated and blood flow in the flap was approximated using dye fluorescence. Seven days later, the amount of viable tissue within the flap was measured by planimetry. After the animals were killed, specimens from both the operated and nonoperated sides of the abdomen were harvested for immunohistologic evidence of VEGF protein expression. Average dye fluorescence indices of the three groups (VEGF cDNA, control plasmid, and saline) 2 hours after pedicle ligation were 35.9, 23.9, and 53.9 percent, respectively (p < 0.05). Compared with the two control groups, flaps receiving VEGF cDNA had significantly greater tissue viability at the end of 7 days: 93.9 versus 28.1 percent for the control plasmid DNA group and 31.9 percent for the saline group (p < 0.05). Immunohistochemical staining documented increased deposition of VEGF protein in flaps that were infused with the VEGF cDNA versus saline alone (p < 0.05). The results indicated that the survival of ischemic tissues can be enhanced by administration of a cDNA encoding VEGF, a protein known to be important in the process of angiogenesis and wound healing.

Early recognition of vascular compromise within microvascular free-tissue transfers is essential if reexploration is to prove successful. Tissue oxygen tension is increasingly recognized to be a sensitive and reliable index of tissue perfusion, and preliminary studies suggest that it may be of value in the assessment of free-flap viability. We describe our investigation into the application of an implantable microcatheter oxygen sensor in the monitoring of free flaps used in head and neck and extremity reconstruction. In a preliminary study using the rabbit model, we sought to evaluate the response of oxygen tension as an index of tissue perfusion in myocutaneous (n = 20) and osteomyocutaneous flaps (n = 5) under conditions of arterial and venous occlusion. A clinical study was then undertaken to evaluate the role of this method in the monitoring of surface and buried free flaps. In 30 heterogeneous free-tissue transfers, sensors placed intraoperatively were used to provide continuous information about flap oxygen tension (mean monitoring period 3.2 +/- 0.8 days). The data generated were correlated with changes in clinical parameters and routine flap observations. Results for experimental and clinical data have confirmed the efficacy of continuous tissue oxygen measurements using this device as a method that provides an objective, recordable index of free-tissue transfer viability in a variety of circumstances and vascular events. Tissue oxygen tension is a suitable index by which to evaluate flap viability with the probe placed in muscle or bone but is unreliable when used for the monitoring of revascularized cutaneous flaps.