title: Assessment of mouse hind limb endothelial function by measuring femoral artery blood flow responses.
abstract: OBJECTIVE
  Substantial progress has been made in cell therapy strategies and in gene- and cytokine-introduced angiogenesis using a variety of mouse models, such as hind limb ischemia models. Endothelial function is an important target in evaluating the effects and outcomes of these potential therapies. Although animal models have been established for estimating endothelium-dependent function by measuring the blood flow responses in carotid and renal arteries and the abdominal aorta, a model specific for an indicated hind limb by measuring femoral artery blood flow (FABF) has not yet been established.
  
  
  METHODS
  A 2-day protocol was designed, including exploration of the segmental femoral artery on the first day, and evaluation of endothelium-dependent vasodilatation function the next day. By placing a transonic flow probe around the left femoral artery, the FABF in response to endothelium-dependent and endothelium-independent vasodilatory stimulations was reproducibly measured. Hemodynamic measurements, including the left FABF and mean arterial pressure, were recorded.
  
  
  RESULTS
  In normal controls, the baseline left FABF averaged 0.12 ± 0.01 mL/min. Acetylcholine increased the FABF up to 0.41 ± 0.02 mL/min. Rose bengal-associated photochemical injury was titrated to cause endothelial dysfunction but without disturbing the integrity of the endothelial layer. The response to acetylcholine significantly decreased 10 minutes after photochemical injury and was further impaired after 1 and 24 hours. However, the response to nitroprusside was preserved. A femoral and iliac artery wire-injury model was also introduced to cause endothelial and smooth muscle cell injury. One day after the wire injury, the responses to acetylcholine and nitroprusside injections were both remarkably attenuated.
  
  
  CONCLUSIONS
  This model can be widely used to analyze the in vivo endothelium-dependent vasodilatation function before and after a variety of therapeutic interventions on a mouse hind limb.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan. bearty@adm.cgmh.org.tw
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Wang
authors.forename: Kuo-Ti
authors.initials: KT
authors.lastname: Chen
authors.forename: Hsiu-Fu
authors.initials: HF
authors.lastname: Mei
authors.forename: Ju-Fang
authors.initials: JF
authors.lastname: Lee
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Cherng
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000293:injuries / Q000503:physiopathology*; D005263:Femoral Artery / Q000293:injuries / Q000503:physiopathology*; D006614:Hindlimb; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000098:blood supply*; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow; D012395:Rose Bengal; D013997:Time Factors; D057772:Vascular System Injuries / Q000209:etiology / Q000503:physiopathology*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D012395:Rose Bengal; D000109:Acetylcholine