PHYSIOLOGICAL ASSESSMENT OF AUGMENTED VASCULARITY INDUCED BY VEGF IN ISCHEMIC RABBIT HINDLIMB

This study was designed to assess the physiological consequences of au gmented vascularity induced by administration of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, in a rabbi t model of hindlimb ischemia. Ten days after excision of the common an d superficial femoral arteries from one hindlimb of 24 New Zealand Whi te rabbits, VEGF (n = 15) or saline (control; n = 9) was selectively i njected into the ipsilateral internal iliac artery. Limb perfusion was evaluated immediately pre-VEGF (baseline) and again at days 10 and 30 . A Doppler guide wire was advanced to the internal iliac artery to re cord flow velocity at rest and at maximum flow velocity provoked by in tra-arterial injection of papaverine. At baseline and at day 10, no di fferences in flow parameters were observed between the control and the VEGF-treated animals. By day 30, however, flow at rest (P < 0.05), ma ximum flow velocity (P < 0.001), and maximum blood flow (P < 0.001) we re all significantly higher in the VEGF-treated group. These physiolog ical findings complement previous anatomic studies by providing eviden ce that a single intra-arterial bolus of VEGF augments flow, particula rly maximum flow, in the rabbit ischemic hindlimb. These data thus sup port the notion that VEGF administration represents a potential treatm ent strategy for certain patients with lower extremity ischemia.