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Abstract

Medicine

Preclinical Model of Hind Limb Ischemia in Diabetic Rabbits

Published: June 2nd, 2019

DOI:

10.3791/58964

1Department of Biomedical Engineering, University of Texas at Austin, 2Division of Cardiology, University of Texas McGovern Medical School, 3Center for Laboratory Animal Medicine and Care, UT Health Science Center at Houston, 4Memorial Herman Heart and Vascular Center, Texas Medical Center, 5Institute for Cellular and Molecular Biology, University of Texas at Austin, 6The Institute for Computational Engineering and Sciences, University of Texas at Austin, 7Institute for Biomaterials, Drug Delivery and Regenerative Medicine, University of Texas at Austin

Abstract

Peripheral vascular disease is a widespread clinical problem that affects millions of patients worldwide. A major consequence of peripheral vascular disease is the development of ischemia. In severe cases, patients can develop critical limb ischemia in which they experience constant pain and an increased risk of limb amputation. Current therapies for peripheral ischemia include bypass surgery or percutaneous interventions such as angioplasty with stenting or atherectomy to restore blood flow. However, these treatments often fail to the continued progression of vascular disease or restenosis or are contraindicated due to the overall poor health of the patient. A promising potential approach to treat peripheral ischemia involves the induction of therapeutic neovascularization to allow the patient to develop collateral vasculature. This newly formed network alleviates peripheral ischemia by restoring perfusion to the affected area. The most frequently employed preclinical model for peripheral ischemia utilizes the creation of hind limb ischemia in healthy rabbits through femoral artery ligation. In the past, however, there has been a strong disconnect between the success of preclinical studies and the failure of clinical trials regarding treatments for peripheral ischemia. Healthy animals typically have robust vascular regeneration in response to surgically induced ischemia, in contrast to the reduced vascularity and regeneration in patients with chronic peripheral ischemia. Here, we describe an optimized animal model for peripheral ischemia in rabbits that includes hyperlipidemia and diabetes. This model has reduced collateral formation and blood pressure recovery in comparison to a model with a higher cholesterol diet. Thus, the model may provide better correlation with human patients with compromised angiogenesis from the common co-morbidities that accompany peripheral vascular disease.

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Keywords Hind Limb Ischemia

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