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Cardiovascular Research 2001 49(3):626-633; doi:10.1016/S0008-6363(00)00199-1
© 2001 by European Society of Cardiology
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Copyright © 2001, European Society of Cardiology

Intramuscular administration of estrogen may promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia

Zenon S. Kyriakidesa,*, Pantelis Petinakisa, Loukas Kaklamanisa, Eftihia Sbarounia, Panagiotis Karayannakosb, Dimitrios Iliopoulosb, Ismene Dontasb and Dimitrios Th. Kremastinosa

a2nd Department of Cardiology and Department of Pathology, Onassis Cardiac Surgery Center, 356 Sygrou Ave., 17674 Athens, Greece
bLaboratory of Experimental Surgery and Surgical Research, School of Medicine, 15B Saint Thomas' str., 11528 Athens, Greece

* Corresponding author. Tel.: +30-1-949-3000, +30-1-949-3357, +30-1-681-3554; fax: +30-1-949-3357 zskyr{at}otenet.gr

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. Methods and 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-β estradiol plasma levels of day 15 (r = 0.58, P = 0.003) and of day 30 (r = 0.46, P<0.02). Conclusion: 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.

KEYWORDS Circulatory physiology; Angiogenesis; Microcirculation; Collateral circulation; Hormones


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