Ariyan Tabesh, Sahil Patel, Tripti Mathur, Priya Dhawan, Zosia Zawacki, Diana Bauer, Pedro Ruivo, Rachel M Russo, Shahram Aarabi
In our porcine survival model, a minimally invasive dual internal-external iliac balloon occlusion technique consistently induced profound hindlimb ischemia consistent with prolonged ALI. The resulting ischemic insult was validated through longitudinal assessment of gait function, neuroelectrophysiologic testing, and terminal histopathologic analysis. This model provides a robust representation of human ALI, enabling study of its long-term functional and histological deficits. By avoiding laparotomy and open arterial clamping, our model minimizes additional surgical insult, reduces systemic injury and eliminates confounding collateral flow.
OBJECTIVE: Large-animal models are essential for studying acute limb ischemia (ALI), yet most existing porcine ALI models are nonsurvival designs intended for short-term physiologic or metabolic investigation. In contrast, current survival models predominantly replicate chronic limb ischemia by surgically ligating the external iliac artery (EIA) or common femoral artery (CFA), an approach that does not generate a complete acute ischemic insult. In our previous studies, single-segment occlusion of the external iliac artery or CFA failed to produce profound unilateral ischemia because of robust collateral reconstitution through the internal iliac system and pelvic vasculature. To address this limitation, we developed a reproducible, minimally invasive survival model of unilateral hindlimb ALI using simultaneous balloon occlusion of the ipsilateral internal artery and EIA (ie, "dual internal-external iliac balloon occlusion"), enabling reliable 7-day survival and longitudinal assessment of functional, electrophysiologic, and histologic outcomes of ALI.
METHODS: Female Yorkshire pigs (50-55 kg) underwent general anesthesia, surgical exposure and vascular access of the common carotid artery, and percutaneous vascular access of the CFA using the Seldinger technique. Angiography confirmed the characteristic porcine anatomy, demonstrating an aortic trifurcation with right and left EIAs and a single internal iliac trunk providing extensive collateral flow. Iterative testing compared tourniquet application, distal aortic balloon occlusion, selective external iliac balloon occlusion, and simultaneous EIA and internal iliac artery balloon occlusion. Sustained 6-hour unilateral hindlimb ischemia was ultimately achieved with balloon occlusion of both the external and internal iliac arteries and validated by angiography, Doppler ultrasound study, and pulse oximetry. Primary outcomes included Tarlov gait score, electrophysiologic testing, and blinded terminal histologic analysis of peroneus tertius muscle and tibial nerve at 7 days postoperatively.
RESULTS: Dual internal-external iliac balloon occlusion consistently produced complete hindlimb ischemia for 6 hours without mortality or systemic morbidity. Pulse oximetry and Doppler ultrasound study confirmed absent distal flow during occlusion, with angiographic validation of no reconstitution. Pigs survived to day 7, exhibiting immediate postoperative functional impairment. Histology showed acute ischemic injury with myofiber necrosis, inflammatory infiltration, coagulative necrosis, mineralization and architectural disruption. Nerve conduction studies demonstrated complete loss of compound muscle action potentials in most specimens.
CONCLUSIONS: In our porcine survival model, a minimally invasive dual internal-external iliac balloon occlusion technique consistently induced profound hindlimb ischemia consistent with prolonged ALI. The resulting ischemic insult was validated through longitudinal assessment of gait function, neuroelectrophysiologic testing, and terminal histopathologic analysis. This model provides a robust representation of human ALI, enabling study of its long-term functional and histological deficits. By avoiding laparotomy and open arterial clamping, our model minimizes additional surgical insult, reduces systemic injury and eliminates confounding collateral flow.
CLINICAL RELEVANCE: Acute limb ischemia is a vascular emergency that can lead to limb loss, long-term disability, and death if not treated promptly. Progress in this field has been limited in part by the lack of a reliable large-animal survival model that reproduces severe acute ischemia. In swine, single-vessel occlusion often fails because pelvic collateral vessels restore distal blood flow. In this study, we developed a minimally invasive dual internal-external iliac balloon occlusion model that produces consistent unilateral hindlimb ischemia with measurable functional, electrophysiologic, and histologic injury. This model may be useful for studying ischemia-reperfusion injury and testing new therapies for acute limb ischemia.