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Home > Vascular Annual Meeting > tormod_limb_ischemia_iliac

Limb Ischemia After Iliac Ligation In Aged Mice Stimulates Angiogenesis Without Arteriogenesis

Tormod S. Westvik1, Akihito Muto1, Tamara N. Fitzgerald1, Stephen P. Maloney2, Jose M. Pimiento2, Tiffany T. Fancher2, Dania Magri1, Hilde H. Westvik1, Omaida C. Velazquez3, Alan Dardik.1,4
1Yale University School of Medicine, New Haven, Conn.;2Saint Mary's Hospital, Waterbury, Conn.;3The Miller School of Medicine at the University of Miami, Miami, Fla.;4VA Connecticut Healthcare System, West Haven, Conn.
OBJECTIVES: Older patients are thought to tolerate acute ischemia more poorly than younger patients. Since aging may depress both angiogenesis and arteriogenesis, we determined the effects of age on both angiogenesis and arteriogenesis, in a model of severe acute limb ischemia.

METHODS: Young adult (3 month) and aged (18 month) C57BL/6 mice underwent right common iliac artery and vein ligation and transection. Data were collected on days 0, 7 and 14. Perfusion was measured with laser Doppler and compared to the contralateral limb. Functional deficits were evaluated with the Tarlov scale. Capillary density and endothelial progenitor cell (EPC) number were determined by direct counting; angiography was performed to directly assess arteriogenesis.

RESULTS: Young adult and aged mice had a similar degree of decreased perfusion after iliac ligation (young, n=15: 20.4±1.9%, vs. old, n=20: 19.6±1.3%; p=.72, ANOVA); however, young mice recovered faster and to a greater degree than aged mice (day 7, 35±6% vs. 17±4%, p=.046; day 14, 60±5% vs. 27±7%, p=.0014). Aged mice had worse functional recovery by day 14 compared to young mice (2.3±.3 vs. 4.3±.4; p=.0021). Aged mice had increased capillary density (day 7, 12.9±4.4 vs. 2.8±0.3 capillaries/hpf; p=.02) and EPC number (day 7, 8.1±0.9 vs. 2.5±1.9 cells; p=0.007) compared to young mice, but diminished collateral supply to the ischemic limb.

CONCLUSIONS: After severe hindlimb ischemia, aged animals become ischemic to a similar degree as young animals, but aged animals have significantly impaired arteriogenesis and functional recovery compared to younger animals. These results suggest that strategies to stimulate arteriogenesis may complement those that increase angiogenesis, and may result in improved relief of ischemia.
AUTHOR DISCLOSURES: T.S. Westvik, None; A. Muto, None; T.N. Fitzgerald, None; S.P. Maloney, None; J.M. Pimiento, None; T.T. Fancher, None; D. Magri, None; H.H. Westvik, None; O.C. Velazquez, None; A. Dardik, None.