title: Towards a more relevant hind limb model of muscle ischaemia.
abstract: Critical limb ischaemia is a severe manifestation of peripheral arterial disease characterised by intractable pain and tissue gangrene. Conventional treatments include percutaneous angioplasty and surgical bypass but up to one third of patients are not amenable to these interventions and will ultimately require amputation. Therapeutic neovascularisation has been proposed as an alternative treatment in these 'no option' patients and both cytokines and cells have shown impressive efficacy in the laboratory. Clinical trials in man, however, have had modest results. This discrepancy has put into question the relevance of the pre-clinical assays that are used to test potential agents. One of the most widely used of these assays is the hind limb ischaemia model that is often performed in young, healthy animals. This review critiques the techniques used to induce and assess ischaemia in this model and outlines the reasons why healthy rodents cannot fully recapitulate critical limb ischaemia in aged patients. Strategies that may produce a hind limb model that better simulates the human condition are proposed.
authors.affiliation: Academic Department of Surgery, Cardiovascular Division, King's College London, BHF Centre of Excellence, NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, 1st Floor North Wing, St Thomas' Hospital, London SE1 7EH, United Kingdom.
authors.forename: Shamim
authors.initials: S
authors.lastname: Lotfi
authors.forename: Ashish S
authors.initials: AS
authors.lastname: Patel
authors.forename: Katherine
authors.initials: K
authors.lastname: Mattock
authors.forename: Stuart
authors.initials: S
authors.lastname: Egginton
authors.forename: Alberto
authors.initials: A
authors.lastname: Smith
authors.forename: Bijan
authors.initials: B
authors.lastname: Modarai
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply* / Q000601:surgery; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D008026:Ligation; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology; D016491:Peripheral Vascular Diseases / Q000628:therapy