title: Physiological assessment of augmented vascularity induced by VEGF in ischemic rabbit hindlimb.
abstract: This study was designed to assess the physiological consequences of augmented vascularity induced by administration of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, in a rabbit model of hindlimb ischemia. Ten days after excision of the common and superficial femoral arteries from one hindlimb of 24 New Zealand White rabbits, VEGF (n = 15) or saline (control; n = 9) was selectively injected 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 record flow velocity at rest and at maximum flow velocity provoked by intra-arterial injection of papaverine. At baseline and at day 10, no differences in flow parameters were observed between the control and the VEGF-treated animals. By day 30, however, flow at rest (P < 0.05), maximum flow velocity (P < 0.001), and maximum blood flow (P < 0.001) were all significantly higher in the VEGF-treated group. These physiological findings complement previous-anatomic studies by providing evidence that a single intra-arterial bolus of VEGF augments flow, particularly maximum flow, in the rabbit ischemic hindlimb. These data thus support the notion that VEGF administration represents a potential treatment strategy for certain patients with lower extremity ischemia.
authors.affiliation: Department of Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135.
authors.forename: C
authors.initials: C
authors.lastname: Bauters
authors.forename: T
authors.initials: T
authors.lastname: Asahara
authors.forename: L P
authors.initials: LP
authors.lastname: Zheng
authors.forename: S
authors.initials: S
authors.lastname: Takeshita
authors.forename: S
authors.initials: S
authors.lastname: Bunting
authors.forename: N
authors.initials: N
authors.lastname: Ferrara
authors.forename: J F
authors.initials: JF
authors.lastname: Symes
authors.forename: J M
authors.initials: JM
authors.lastname: Isner
mesh_terms: D000818:Animals; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D005263:Femoral Artery / Q000502:physiology*; D006614:Hindlimb / Q000098:blood supply; D007083:Iliac Artery / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology*; D008222:Lymphokines / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D009132:Muscles / Q000098:blood supply*; D010208:Papaverine / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D010208:Papaverine