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


METHODS
C57BL/6 mice were subjected to TAR under hypothermic (34 degrees C) or normothermic (38 degrees 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.


RESULTS
Normothermic 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.


CONCLUSIONS
Systemic 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.
Kang
Jeanwan
J
Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Mass, USA.
Albadawi
Hassan
H
Casey
Patrick J
PJ
Abbruzzese
Thomas A
TA
Patel
Virendra I
VI
Yoo
Hyung-Jin
HJ
Cambria
Richard P
RP
Watkins
Michael T
MT
D000818:Animals; D000870:Anterior Horn Cells / Q000473:pathology / Q000503:physiopathology; D001013:Aorta, Thoracic / Q000601:surgery*; D002470:Cell Survival; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D007036:Hypothermia, Induced; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000276:immunology; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009460:Neurologic Examination; D010243:Paralysis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012720:Severity of Illness Index; D020760:Spinal Cord Ischemia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors
D018925:Chemokines; D018836:Inflammation Mediators; D015850:Interleukin-6; C074302:keratinocyte-derived chemokines; D009195:Peroxidase