Animal experimental models of ischemic limbs - A systematic review.

BACKGROUND: The objective of this systematic review is to summarize the available animal models of ischemic limbs, and to provide an overview of the advantages and disadvantages of each animal model and individual method of limb ischemia creation. METHODS: A review of literature was conducted using the PubMed and Web of Science pages. Various types of experimental animals and surgical approaches used in creating ischemic limbs were evaluated. Other outcomes of interest were the specific characteristics of the individual experimental animals, and duration of tissue ischemia. RESULTS: The most commonly used experimental animals were mice, followed by rabbits, rats, pigs, miniature pigs, and sheep. Single or double arterial ligation and excision of the entire femoral artery was the most often used method of ischemic limb creation. Other methods comprised single or double arterial electrocoagulation, use of ameroid constrictors, photochemically induced thrombosis, and different types of endovascular methods. The shortest duration of tissue ischemia was 7 days, the longest 90 days. CONCLUSIONS: This review shows that mice are among the most commonly used animals in limb ischemia research. Simple ligation and excision of the femoral artery is the most common method of creating an ischemic limb; nevertheless, it can result in acute rather than chronic ischemia. A two-stage sequential approach and methods using ameroid constrictors or endovascular blinded stent grafts are more suitable for creating a gradual arterial occlusion typically seen in humans. Selecting the right mouse strain or animal with artificially produced diabetes or hyperlipidaemia is crucial in chronic ischemic limb research. Moreover, the observation period following the onset of ischemia should last at least 14 days, preferably 4 weeks.

Animal experimental models of ischemic wounds - A review of literature.

Critical limb ischemia is a serious form of peripheral arterial disease (PAD). The consequences of lower limb ischemia are pain, claudication and chronic non-healing wounds. Patients with diabetes are especially at a high risk for developing non-healing ulcers. The most serious complication is major amputation. For this reason, there is a significant medical requirement to develop new therapies in order to prevent the progression of PAD. For research purposes, it is crucial to find an appropriate model of chronic ischemia to explore the processes of wound healing. According to recently acquired information, rodents are currently the most commonly used animals in these types of studies. The main advantage of using small animals is the low financial cost due to the relatively small demand for food, water and living space. The disadvantage is their anatomy, which is different from that of humans. Larger animals have a more human-like anatomy and physiology, but they require more expense and space for housing. A bipedicle skin flap and its modifications are popular models for ischemic wounds. In order to secure healing through re-epithelisation, as opposed to contraction in rodents, there is a need to remove the panniculus carnosus muscle. Wounds in other experimental animals heal primarily through re-epithelisation. The application of a silicone mesh underneath the flap prevents vascular regrowth in ischemic tissue. There is an ongoing effort to create in vivo diabetic models for chronic ulcer research. This work presents an overview of existing animal models of ischemic wounds.