Hemorrhagic shock worsens neuromuscular recovery in a porcine model of hind limb vascular injury and ischemia-reperfusion

Abstract

In order to advance beyond basic statistical limb salvage to improved functional or quality limb salvage, a better understanding of the ischemic threshold of the limb is required. To date, models of extremity ischemia and reperfusion involve small animals and few include survival with physiologic measures of nerve and muscle recovery. In addition, the effect of hemorrhagic shock on the ischemic threshold of the extremity is unknown. This study characterized the effect of class III hemorrhagic shock on the ischemic threshold of the extremity in a large-animal model of neuromuscular recovery. Yorkshire/Landrace-cross swine (weight, 70-90 kg) were randomized to iliac artery repair either immediately or at 1, 3, or 6 hours after vessel loop occlusion and arteriotomy. A fifth group underwent excision of the arterial segment without repair to represent ligation. Class III shock was created by removing 35% of total blood volume using a variable rate model. Animals were monitored for 14 days to serially collect markers of functional recovery. Animals with ≤1 hour ischemia (control) had clinically normal limb function by the end of the 2-week observation period, with minimal muscle and nerve changes on histology. Separate analysis of contralateral, nonexperimental limbs revealed normal histology and function. After 3 hours of ischemia, functional recovery was impaired, with moderate-to-severe degeneration of nerve and muscle noted on histology. Animals undergoing 6 hours of ischemia or ligation had minimal electromyelography response and severe systemic inflammation, which correlated with severe muscle and nerve degeneration. Concurrent class III hemorrhagic shock was associated with a decrement in neuromuscular recovery across all groups but was greatest in groups undergoing ≥3 hours of extremity ischemia (P < .01). This study demonstrates the feasibility of combined hemorrhagic shock and extremity ischemia-reperfusion in a large-animal survival model. The presence of hemorrhagic shock compounds the effect of extremity ischemia, reducing the ischemic threshold of the limb to <3 hours. Strategies to improve functional salvage after extremity vascular injury in the setting of shock should include attempts at restoration of flow ≤60 minutes.