title: Intramuscular administration of estrogen may promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia.
abstract: OBJECTIVE
  Promoting angiogenesis may be an effective treatment for patients with diffuse peripheral vascular disease. This study investigated whether estrogen can promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia.
  
  
  RESULTS
  Ischemia was induced in one hindlimb of 24 oophorectomized New Zealand White rabbits. Ten days later (day 0), they were randomized into 4 groups for intramuscular treatment in the ischemic limb: controls receiving saline at day 0; Estrogen-1 group receiving estradiol valerate, modified release (EVMR), 1 mg/kg at day 0; Estrogen-2 group receiving EVMR 1 mg/kg at days 0 and 15; and Estrogen-3 group receiving EVMR 2 mg/kg at day 0. Revascularization was evaluated by clinical indexes, such as ischemic/normal limb systolic blood pressure (BPR), and capillary density/muscle fiber in the abductor muscle of the ischemic limb at the time of death (day 30). At day 30 the BPR was increased in all groups (0.39+/-0.08 in the controls, 0.52+/-0.11 in the Estrogen-1 group, 0.65+/-0.13 in the Estrogen-2 group and 0.61+/-0.16 in the Estrogen-3 group, F=2.39, P=0.04). The capillary/muscle fiber at day 30 was 0.87+/-0.09, 1.08+/-0.15, 1.01+/-0.14 and 1.10+/-0.9 (F=5.01, P=0.01), respectively, in the 4 groups. The capillary/muscle fiber was related to BPR (r=0.48, P<0.02) and to 17-beta estradiol plasma levels of day 15 (r=0.58, P=0.003) and of day 30 (r=0.46, P<0.02).
  
  
  CONCLUSIONS
  Administration of estrogen promotes angiogenesis and perfusion in ischemic rabbit hindlimbs. Thus, estrogen may represent a new therapeutic modality in the management of arterial insufficiency.
authors.affiliation: 2nd Department of Cardiology and Department of Pathology, Onassis Cardiac Surgery Center, 356 Sygrou Ave., 17674, Athens, Greece. zskyr@otenet.gr
authors.forename: Z S
authors.initials: ZS
authors.lastname: Kyriakides
authors.forename: P
authors.initials: P
authors.lastname: Petinakis
authors.forename: L
authors.initials: L
authors.lastname: Kaklamanis
authors.forename: E
authors.initials: E
authors.lastname: Sbarouni
authors.forename: P
authors.initials: P
authors.lastname: Karayannakos
authors.forename: D
authors.initials: D
authors.lastname: Iliopoulos
authors.forename: I
authors.initials: I
authors.lastname: Dontas
authors.forename: D T
authors.initials: DT
authors.lastname: Kremastinos
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries; D003097:Collateral Circulation; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D007273:Injections, Intramuscular; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D017078:Laser-Doppler Flowmetry; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D018919:Neovascularization, Physiologic; D010052:Ovariectomy; D010477:Perfusion; D011817:Rabbits; D011897:Random Allocation; D012044:Regression Analysis
chemical_list: D003692:Delayed-Action Preparations; D004958:Estradiol