Fast rewarming after deep hypothermic circulatory arrest in rats impairs histologic outcome and increases NFκB expression in the brain

Objective: Deep hypothermia is used as a neuroprotectant during cardiac surgery utilizing deep hypothermic circulatory arrest (DHCA), although the ideal rewarming strategy is not known yet. Some of the neuroprotective properties of hypothermia seem to be mediated by Nuclear Factor Kappa B (NFκB) as an important transcription factor. The current study was designed to investigate the effect of the rewarming rate on histologic outcome and cerebral NFκB expression one day following DHCA in rats. Methods: With IRB approval, 20 rats were cannulated for cardiopulmonary bypass (CPB), cooled to a rectal temperature of 15-18°C, subjected to 45min of DHCA and randomly assigned to either a slow (40 min) or a fast (20 min) rewarming protocol. At 24 hours post DHCA, the number of eosinophilic neurons was analyzed with hematoxylin and eosin (HE) staining, and NFκB expression immunohistochemically. The two experimental groups were compared with untreated control rats. Results: HE staining showed more eosinophilic neurons in the motor cortex following fast rewarming (60 [15-388]) compared to slow rewarming (15 [10—21]) (p<0.05). Neuronal expression of NFκB was increased in the fast rewarming group in both brain areas, the motor cortex (fast: 258 [135-393]; slow: 165 [80—212]; control: 73 [44-111]) as well as the hippocampus (fast: 243 [209-314]; slow: 202 [187-239]; control: 86 [68-108]) (p<0.05). Hyperthermic episodes were strictly avoided. Conclusions: Fast rewarming with strict avoidance of hyperthermia after DHCA in rats was accompanied by pronounced histologic damage and accentuated cerebral NFκB expression.

[1]  T. Nichols NF-kappaB and reperfusion injury. , 2004, Drug news & perspectives.

[2]  J. Coselli,et al.  Temperature management after hypothermic circulatory arrest. , 2002, The Journal of thoracic and cardiovascular surgery.

[3]  R. Giffard,et al.  Inflammation and NFκB activation is decreased by hypothermia following global cerebral ischemia , 2009, Neurobiology of Disease.

[4]  M. Yenari,et al.  Influence of hypothermia on post-ischemic inflammation: Role of nuclear factor kappa B (NFκB) , 2006, Neurochemistry International.

[5]  S. Hirai Systemic inflammatory response syndrome after cardiac surgery under cardiopulmonary bypass. , 2003, Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia.

[6]  W. Mcbride,et al.  Cytokine balance and immunosuppressive changes at cardiac surgery: contrasting response between patients and isolated CPB circuits. , 1995, British journal of anaesthesia.

[7]  G. Clifton,et al.  Relationship between body and brain temperature in traumatically brain-injured rodents. , 1991, Journal of neurosurgery.

[8]  D. Shera,et al.  Preoperative Brain Injury in Transposition of the Great Arteries Is Associated With Oxygenation and Time to Surgery, Not Balloon Atrial Septostomy , 2009, Circulation.

[9]  F. Dexter,et al.  Rapid Rewarming Causes an Increase in the Cerebral Metabolic Rate for Oxygen that Is Temporarily Unmatched by Cerebral Blood Flow: A Study during Cardiopulmonary Bypass in Rabbits , 1996, Anesthesiology.

[10]  Manfred Blobner,et al.  Neurologic outcome after cardiopulmonary bypass with deep hypothermic circulatory arrest in rats: description of a new model. , 2006, The Journal of thoracic and cardiovascular surgery.

[11]  S. Abbasi,et al.  Factors affecting postoperative morbidity and mortality in isolated coronary artery bypass graft surgery , 2008, Surgery Today.

[12]  E. Kochs,et al.  Long-term assessment of NFκB expression in the brain and neurologic outcome following deep hypothermic circulatory arrest in rats , 2009, Perfusion.

[13]  J. Blumenthal,et al.  The Rewarming Rate and Increased Peak Temperature Alter Neurocognitive Outcome After Cardiac Surgery , 2002 .