Punam P Parikh1, Diego Castilla2, Roberta M Lassance-Soares2, Hongwei Shao2, Manuela Regueiro2, Yan Li2, Roberto Vazquez-Padron2, Keith A Webster3, Zhao-Jun Liu2, Omaida C Velazquez2. 1. DeWitt-Daughtry Family Department of Surgery, Division of Vascular Surgery, University of Miami Miller School of Medicine, Miami, FL. Electronic address: Pparikh@med.miami.edu. 2. DeWitt-Daughtry Family Department of Surgery, Division of Vascular Surgery, University of Miami Miller School of Medicine, Miami, FL. 3. Department of Molecular and Cellular Pharmacology and the Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, FL.
Abstract
BACKGROUND: Lack of a reliable hind limb gangrene animal model limits preclinical studies of gangrene, a severe form of critical limb ischemia. We develop a novel mouse hind limb gangrene model to facilitate translational studies. METHODS: BALB/c, FVB, and C57BL/6 mice underwent femoral artery ligation (FAL) with or without administration of NG-nitro-L-arginine methyl ester (L-NAME), an endothelial nitric oxide synthase inhibitor. Gangrene was assessed using standardized ischemia scores ranging from 0 (no gangrene) to 12 (forefoot gangrene). Laser Doppler imaging (LDI) and DiI perfusion quantified hind limb reperfusion postoperatively. RESULTS: BALB/c develops gangrene with FAL-only (n = 11/11, 100% gangrene incidence), showing mean limb ischemia score of 12 on postoperative days (PODs) 7 and 14 with LDI ranging from 0.08 to 0.12 on respective PODs. Most FVB did not develop gangrene with FAL-only (n = 3/9, 33% gangrene incidence) but with FAL and L-NAME (n = 9/9, 100% gangrene incidence). Mean limb ischemia scores for FVB undergoing FAL with L-NAME were significantly higher than for FVB receiving FAL-only. LDI score and capillary density by POD 28 were significantly lower in FVB undergoing FAL with L-NAME. C57BL/6 did not develop gangrene with FAL-only or FAL and L-NAME. CONCLUSIONS: Reproducible murine gangrene models may elucidate molecular mechanisms for gangrene development, facilitating therapeutic intervention.
BACKGROUND: Lack of a reliable hind limb gangrene animal model limits preclinical studies of gangrene, a severe form of critical limb ischemia. We develop a novel mouse hind limb gangrene model to facilitate translational studies. METHODS: BALB/c, FVB, and C57BL/6 mice underwent femoral artery ligation (FAL) with or without administration of NG-nitro-L-arginine methyl ester (L-NAME), an endothelial nitric oxide synthase inhibitor. Gangrene was assessed using standardized ischemia scores ranging from 0 (no gangrene) to 12 (forefoot gangrene). Laser Doppler imaging (LDI) and DiI perfusion quantified hind limb reperfusion postoperatively. RESULTS: BALB/c develops gangrene with FAL-only (n = 11/11, 100% gangrene incidence), showing mean limb ischemia score of 12 on postoperative days (PODs) 7 and 14 with LDI ranging from 0.08 to 0.12 on respective PODs. Most FVB did not develop gangrene with FAL-only (n = 3/9, 33% gangrene incidence) but with FAL and L-NAME (n = 9/9, 100% gangrene incidence). Mean limb ischemia scores for FVB undergoing FAL with L-NAME were significantly higher than for FVB receiving FAL-only. LDI score and capillary density by POD 28 were significantly lower in FVB undergoing FAL with L-NAME. C57BL/6 did not develop gangrene with FAL-only or FAL and L-NAME. CONCLUSIONS: Reproducible murinegangrene models may elucidate molecular mechanisms for gangrene development, facilitating therapeutic intervention.
Authors: Antoine J Ribieras; Yulexi Y Ortiz; Yan Li; Carlos T Huerta; Nga Le; Hongwei Shao; Roberto I Vazquez-Padron; Zhao-Jun Liu; Omaida C Velazquez Journal: Front Cardiovasc Med Date: 2022-06-16
Authors: Hallie J Quiroz; Samantha F Valencia; Hongwei Shao; Yan Li; Yulexi Y Ortiz; Punam P Parikh; Roberta M Lassance-Soares; Roberto I Vazquez-Padron; Zhao-Jun Liu; Omaida C Velazquez Journal: Front Cardiovasc Med Date: 2022-01-31
Authors: Huiyin Tu; Junliang Qian; Dongze Zhang; Aaron N Barksdale; Michael C Wadman; Iraklis I Pipinos; Yu-Long Li Journal: Front Physiol Date: 2022-09-16 Impact factor: 4.755