Preclinical models of human peripheral arterial occlusive disease: implications for investigation of therapeutic agents

1 Division of Cardiology, Department of Medicine, Durham Department of Veterans Affairs and Duke University Medical Center, Durham, North Carolina 27705; 2 Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri 65212; and 3 Procter and Gamble Pharmaceuticals, Mason, Ohio 45069 Submitted 2 February 2004 ; accepted in final form 16 April 2004 Peripheral arterial occlusive disease (PAOD) is now recognized as a combination of clinical syndromes that are associated with significant morbidity and mortality. The primary pathophysiology of PAOD is impaired perfusion to the lower extremity. Effective pharmacotherapy designed to increase perfusion in PAOD is lacking, and revascularization options are suboptimal. New and more efficacious therapies that improve blood flow are definitely needed, and thus designing, describing, and validating these new therapies in preclinical PAOD models will be essential. This study describes the various preclinical PAOD models presently in use, correlates the models to human PAOD, and reviews the available end points that can be used to detect a response to therapy. angiogenesis; endothelial cells; growth factors; perfusion; vascular surgery Address for reprint requests and other correspondence: B. H. Annex, Durham VA and Duke University Medical Center, 508 Fulton St. (Box 111A), Durham, NC 27705 (E-mail: annex001{at}mc.duke.edu ).