The effects of systemic hypothermia on a murine model of thoracic aortic ischemia reperfusion

IntroductionHypothermia is widely used to mediate ischemia-reperfusion injury associated with repair of the thoracoabdominal aorta. Experiments were designed in a murine model of thoracic aortic ischemia-reperfusion (TAR) to evaluate the effect of moderate systemic hypothermia on neurologic function, spinal cord morphology, and indices of inflammation in critical organs.MethodsC57BL/6 mice were subjected to TAR under hypothermic (34°C) or normothermic (38°C) conditions, followed by 24 or 48 hours of normothermic reperfusion. Neurologic functions were assessed during reperfusion. Spinal cords were examined at 24 and 48 hours after reperfusion, and the degree of injury qualified by counting the number of viable motor neurons within the anterior horns. Keratinocyte chemokine, interleukin-6, and myeloperoxidase levels were measured from lung, liver, and kidney at 24 and 48 hours.ResultsNormothermic TAR resulted in a dense neurologic deficit in all mice throughout the reperfusion period. Mice subjected to TAR under hypothermic conditions had transient, mild neurologic deficit during the initial periods of reperfusion. Between 24 and 48 hours, delayed paralysis developed in half of these mice, whereas the other half remained neurologically intact. Spinal cord histology showed a graded degree of injury that correlated with neurologic function. There was no correlation between markers of inflammation in various organs and neurologic outcomes following TAR.ConclusionSystemic moderate hypothermia was protective against immediate paralysis after TAR in all cases and was associated with delayed paralysis in 50% of mice. This study suggests that delayed-onset paralysis may be the result of a local insult, rather than a systemic inflammatory event, precipitating spinal cord injury.

Clinical RelevanceSpinal cord injury is one of the most devastating complications of vascular surgery on the thoracoabdominal aorta. This study used a murine model that replicates the phenotypic and histologic characteristics of spinal cord injury in humans after thoracic aortic ischemia, followed by reperfusion. The findings indicate that subtle injury that exhibits minimal disability during the early periods after thoracic aortic ischemia-reperfusion may be a harbinger of delayed paralysis. This early injury, obvious in mice, may not be evident in an intubated critically ill patient. Delayed paralysis in mice was not associated with a delayed systemic inflammatory response but was associated with direct evidence of graded motor neuron injury. These data suggest that early intervention during the ischemic period may be necessary to avoid creating a scenario where the spinal cord will be susceptible to delayed injury.