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Predictive Value of the Mouse Model of Critical Limb Ischemia: Methodological Differences May Dictate the Outcome of Preclinical Efficacy
Author(s) -
Brooks Ben,
McKee Jeff
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1092.22
Subject(s) - hindlimb , perfusion , ischemia , vasculogenesis , medicine , saline , anesthesia , endocrinology , chemistry , in vitro , endothelial stem cell , biochemistry
The mouse model of limb ischemia simulating peripheral vascular disease is used to evaluate the efficacy of therapeutics to promote vasculogenesis. One major criticism of this model is the absence of a well‐characterized positive control. Objectives To evaluate the use of sodium nitrite (NaNO 2 ) as a positive control in immunocompromised mice used routinely to evaluate human cell‐based, proangiogenic therapeutics. Methods Nude mice and C57BL/NHsd mice underwent surgically induced, unilateral hind limb ischemia. Animals received either 165 mg/kg NaNO 2 in phosphate buffered saline (PBS) or PBS intraperitoneally twice daily for 7 days. Hind limb perfusion was evaluated on days 1, 4, 7, and 14 post‐surgery. Results No increase in hind limb perfusion was observed in wild‐type or nude mice treated with NaNO 2 as compared with PBS controls. Interestingly, nude mice, in general, exhibited significantly lower LDI perfusion ratios over time as compared with wild‐type mice. Conclusions These data conflict a previous report indicating that sodium nitrite significantly increased hind limb perfusion in wild‐type mice using a similar mouse model of limb ischemia. The lower perfusion recovery profiles in nude mice suggest less preexisting collateral vessels and/or a reduced capacity to form new vessels as compared with wild‐type mice.