Therapeutic Limb Hypothermia Preserves Neurophysiologic Function and Reduces Tissue Injury in a Novel Porcine Survival Model of Acute Hindlimb Ischemia

Background: Acute limb ischemia carries high morbidity and risk of limb loss. Prior animal models were limited to non-survival designs and biochemical endpoints, precluding assessment of long-term outcomes. We developed a porcine survival model of ischemia–reperfusion injury to evaluate therapeutic limb hypothermia with functional, neurophysiologic, and histopathologic endpoints. Methods: Ten female Yorkshire pigs underwent unilateral hindlimb ischemia via balloon occlusion of the ipsilateral external and internal iliac arteries for six hours, confirmed by angiography, and were randomized to hypothermia (5°C) or normothermia, with the contralateral limb as control. Hypothermia was applied via a closed-loop limb-cooling device to achieve goal muscle temperature. Animals were monitored for 7 days with daily Tarlov assessment and underwent terminal neurophysiologic testing and muscle/nerve biopsy on day 7. Results: Hypothermia-treated limbs showed significantly preserved sensory and motor nerve conduction at POD7 versus marked loss in controls (p = 0.008 for both SNAP and CMAP preservation), and markedly reduced histologic muscle injury across degeneration, necrosis, inflammation, and regeneration (cumulative score, p < 0.001). Nerve histologic injury did not differ significantly between groups (p = 0.45), and gait recovery showed a favorable but non-significant trend versus controls (p = 0.34). Conclusion: Localized limb hypothermia preserves neurophysiologic function and reduces tissue injury after acute limb ischemia (p ≤ 0.008 for both), with a favorable but non-significant trend in functional recovery. This novel large-animal model is relevant for studying human acute limb ischemia and reperfusion injury in traumatic or embolic settings.