Physiological assessment of augmented vascularity induced by VEGF in ischemic rabbit hindlimb.
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.
Bauters
C
C
Department of Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135.
Asahara
T
T
Zheng
L P
LP
Takeshita
S
S
Bunting
S
S
Ferrara
N
N
Symes
J F
JF
Isner
J M
JM
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
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D010208:Papaverine