Molecular signatures of neurotoxicity in cardiac surgery with cardiopulmonary bypass
Background Neurobehavioral disorders, and stroke are frequently reported after cardiac surgery. Although cerebral neuronal damage may be caused by transient or outlasting hypoxia as a consequence of embolism, the underlying mechanisms remain unsettled. Objective: To analyze changes in the biochemical markers of neurotoxicity in 26 patients who underwent CABG (n=14), valve replacement (n=10) or other cardiac surgery (n=2) with cardiopulmonary bypass (CPB). Methods: The surgical protocol recorded the total perfusion time, cross-clamp time, minimum nasopharyngeal temperature and mean arterial pressure (MAP). Canadian stroke scale was evaluated prior surgery, at 24h and 48h after CPB. Blood samples were obtained immediately before surgery, just after surgery, at 6h, and at 24h after CPB. Mean perfusion time was 105±36 min, mean cross-clamp time was 67±27 min, and mean lower temperature was 30.6±1.7°C. MAP was lower than 50 mmHg in 4 patients, and remained between 50 and 90 mmHg in 22. Results: Glutamate concentrations increased four fold, and L-arginine and GABA levels decreased 30%, just after surgery (all p<0.001). Amino acid concentrations returned to normal values at 24h. Glutamate, L-arginine and GABA levels after surgery correlated with the cross-clamp time (r=0.86, r=-0.69, and r=-0.56, respectively) (all p<0.01), but not with the lower body temperature during intervention. Glutamate levels were higher in patients with MAP<50mmHg (p=0.022). The highest glutamate concentration was observed in a patient who developed a cerebral infarct. No significant changes were found in proinflammatory parameters in blood (IL-6, TNF-α, ICAM-1 and VCAM-1). Conclusions: CPB is associated with an important increase of excitatory, and decrease of inhibitory amino acids in the blood. L-arginine consumption might reflect nitric oxide generation. These findings suggest that cerebral excitotoxicity may occur in cardiac surgery. Prophylactic neuroprotection in CPB should be investigated in clinical trials.