Collateral Development and Arteriogenesis in Hindlimbs of Swine After Ligation of Arterial Inflow

Gao, Yue; Aravind, Shruthi; Patel, Nishant; Fuglestad, Matthew A.; Ungar, Joshua S.; Mietus, Constance J.; Li, Shuai; Casale, George P.; Pipinos, Iraklis I.; Carlson, Mark A.

doi:10.1016/j.jss.2019.12.005

Cited by 16 publications

(14 citation statements)

References 27 publications

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“…Further, tourniquet application never results in chronic ischemia even though it produces acute ischemia making the animal model useful only to limited applications. To overcome these shortfalls, an animal model of surgical ligation followed by excision of major supply artery closer to the aorta at the level of the common iliac artery and the ablation of potential sources of collateral supply to produce profound chronic effects rather than performing simple distal occlusion of common femoral artery is demonstrated previously in rabbits (Gao et al, 2020;Waters et al, 2004). This technique documents a persistent model preventing short-bridging collateral vessel formation by ligating above the level of inguinal ligament.…”

Section: Discussionmentioning

confidence: 99%

A report on less-severe, long-duration persistent hind-limb ischemia surgical rabbit model

HARIKRISHNAN¹,

SHENOY²,

RANARAJ³

et al. 2022

J Hellenic Vet Med Soc

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Development of a persistent hind limb ischemia rabbit model without excessive adverse symptoms and compromised animal welfare. New Zealand White (n=18, male and female) rabbits of 3-4 months of age and 3.0± 0.1 Kg body weight were used. The surgical technique for ischemia avoided the ligation of vessels above the inguinal ligament and included only the ligation and complete excision of the common and superficial femoral arteries along with all their branches up to popliteal and saphenous arteries. Study duration was 84 days. All animals completed the study period uneventfully. The activity of the animals remained unaffected throughout the study except for the first post-operative day. Adverse symptoms of other models such as loss of limb due to necrosis, loss of nails and necrosis of skin were not observed while successful ischemia was confirmed. There was a significant decrease (P=0.0381) in ischemic right limb circumference.Terminal angiography by abdominal aortic cannulation in the animals demonstrated negligible amount of angiogenesis at the distal ischemic thigh in comparison to the control limb (P=0.001). This study reports successful development of a refined chronic hindlimb ischemia rabbit model.

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Section: Discussionmentioning

confidence: 99%

A report on less-severe, long-duration persistent hind-limb ischemia surgical rabbit model

HARIKRISHNAN¹,

SHENOY²,

RANARAJ³

et al. 2022

J Hellenic Vet Med Soc

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“…20,21,74−78 They have also determined the optimal sites of arterial disruption in swine to produce an accurate and clinically relevant mimic of human claudication. 79,80 We would like to further validate our hydrogels and evaluate the choice of the injection site, timing, and dose of hydrogels in the swine PAD model. 11 All of these will provide valuable knowledge about our hydrogels as a potential translational therapy for human PAD patients.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, while mice or rats are useful in evaluating the biocompatibility and efficiency of hydrogels, the small size of the animal (and its arteries, muscles, and organs) may limit our evaluation of more applicable patient-centered delivery methods and invasive diagnostic and functional testing. Our next step is to validate our optimized hydrogels in a clinically-relevant swine PAD model. , The team of Dr. Pipinos has demonstrated the ability of swine to recapitulate the most important pathophysiologic characteristics of human PAD, including persistently decreased hindlimb hemodynamics/perfusion, decreased treadmill performance, and ischemic myopathy. ,,− They have also determined the optimal sites of arterial disruption in swine to produce an accurate and clinically relevant mimic of human claudication. , We would like to further validate our hydrogels and evaluate the choice of the injection site, timing, and dose of hydrogels in the swine PAD model . All of these will provide valuable knowledge about our hydrogels as a potential translational therapy for human PAD patients.…”

Section: Discussionmentioning

confidence: 99%

Antioxidative and Angiogenic Hyaluronic Acid-Based Hydrogel for the Treatment of Peripheral Artery Disease

Cui

Nie

Liu

et al. 2021

ACS Appl. Mater. Interfaces

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Peripheral arterial disease (PAD) is a progressive atherosclerotic disorder characterized by blockages of the arteries supplying the lower extremities. Ischemia initiates oxidative damage and mitochondrial dysfunction in the legs of PAD patients, causing injury to the tissues of the leg, significant decline in walking performance, leg pain while walking, and in the most severe cases, nonhealing ulcers and gangrene. Current clinical trials based on cells/stem cells, the trophic factor, or gene therapy systems have shown some promising results for the treatment of PAD. Biomaterial matrices have been explored in animal models of PAD to enhance these therapies. However, current biomaterial approaches have not fully met the essential requirements for minimally invasive intramuscular delivery to the leg. Ideally, a biomaterial should present properties to ameliorate oxidative stress/ damage and failure of angiogenesis. Recently, we have created a thermosensitive hyaluronic acid (HA) hydrogel with antioxidant capacity and skeletal muscle-matching stiffness. Here, we further optimized HA hydrogels with the cell adhesion peptide RGD to facilitate the development of vascular-like structures in vitro. The optimized HA hydrogel reduced intracellular reactive oxygen species levels and preserved vascular-like structures against H 2 O 2 -induced damage in vitro. HA hydrogels also provided prolonged release of the vascular endothelial growth factor (VEGF). After injection into rat ischemic hindlimb muscles, this VEGF-releasing hydrogel reduced lipid oxidation, regulated oxidative-related genes, enhanced local blood flow in the muscle, and improved running capacity of the treated rats. Our HA hydrogel system holds great potential for the treatment of the ischemic legs of patients with PAD.

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“…It is worth noting that very few studies have been performed in clinically relevant animals that have characteristics that are closer to human PAD such as size, comorbidities, metabolic syndrome, and increased age [ 60 , 61 ]. Recently Anderson et al have applied alginate hydrogels to provide sustained release of VEGF and insulin-like growth factor (IGF) into ischemic hind limbs in middle-aged and old mice and in young rabbits [ 62 ].…”

Section: Bioengineering Approaches For the Treatment Of Padmentioning

confidence: 99%

Bioengineering strategies for the treatment of peripheral arterial disease

Kitzerow

Nie

et al. 2021

Bioactive Materials

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Peripheral arterial disease (PAD) is a progressive atherosclerotic disorder characterized by narrowing and occlusion of arteries supplying the lower extremities. Approximately 200 million people worldwide are affected by PAD. The current standard of operative care is open or endovascular revascularization in which blood flow restoration is the goal. However, many patients are not appropriate candidates for these treatments and are subject to continuous ischemia of their lower limbs. Current research in the therapy of PAD involves developing modalities that induce angiogenesis, but the results of simple cell transplantation or growth factor delivery have been found to be relatively poor mainly due to difficulties in stem cell retention and survival and rapid diffusion and enzymolysis of growth factors following injection of these agents in the affected tissues. Biomaterials, including hydrogels, have the capability to protect stem cells during injection and to support cell survival. Hydrogels can also provide a sustained release of growth factors at the injection site. This review will focus on biomaterial systems currently being investigated as carriers for cell and growth factor delivery, and will also discuss biomaterials as a potential stand-alone method for the treatment of PAD. Finally, the challenges of development and use of biomaterials systems for PAD treatment will be reviewed.

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Collateral Development and Arteriogenesis in Hindlimbs of Swine After Ligation of Arterial Inflow

Cited by 16 publications

References 27 publications

A report on less-severe, long-duration persistent hind-limb ischemia surgical rabbit model

A report on less-severe, long-duration persistent hind-limb ischemia surgical rabbit model

Antioxidative and Angiogenic Hyaluronic Acid-Based Hydrogel for the Treatment of Peripheral Artery Disease

Bioengineering strategies for the treatment of peripheral arterial disease

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