Introduction: Vascular Endothelial Growth Factor (VEGF) reportedly improves ischemic flap survival when administered. The purpose of this study was to quantify endogenous VEGF expression in flaps after ischemia-reperfusion injury. In addition, VEGF expression was localized in muscle and skin.
Methods: Twelve Latissimus dorsi myocutaneous flaps (15x10 cm) were elevated bilaterally in six male pigs (25 kg). One flap was randomly assigned to 4 hrs of ischemia by occluding the pedicle, followed by 2 hrs of reperfusion. Contralateral flaps were controls. Skin perfusion in flap base, middle, and tip was measured as baseline, after elevation, after ischemia, and during reperfusion. Microvascular length density was measured in flap muscle using intravital microscopy. Biopsies were taken at the end from each flap zone and adjacent tissue for VEGF levels and immunohistochemistry.
Results: Perfusion differed among flap zones during ischemia and reperfusion. No differences were found in microvascular density in ischemic versus control flaps. VEGF levels (pg/mg protein; mean±SEM) were:
Muscle: Control: Base 71.0±14.6, Middle 53.1±7.0, Tip 43.2±9.7, Adjacent 39.0±5.9; Ischemic: Base 65.6±18.5, Middle 54.8±13.5, Tip 30.3±8.2.
Skin: Control: Base 2.2±1.4, Middle 3.4±1.7, Tip 6.8±1.9, Adjacent 5.0±4.9; Ischemic: Base 9.6±3.0, Middle 9.9±2.4, Tip 4.3±1.6
Muscle VEGF decreased from base to tip and exceeded skin VEGF. Flaps had higher VEGF than adjacent muscle (p£0.05). Ischemic skin VEGF was higher than controls in base and middle only (p£0.05). Flap epidermis was negative for VEGF staining, but dermis and subcutaneous tissue were positive. Flap muscle interfascicular septae stained well, with occasional myocyte staining. Ischemic flap skin showed increased VEGF staining compared to controls (p < 0.05). In muscle, only the base showed increased VEGF staining with ischemia (p < 0.05). Conclusion: Moderate ischemia stimulates VEGF protein expression in muscle and skin. However, endogenous levels do not reach reported levels following exogenous administration.