Cerebral tumor necrosis factor α expression and long-term neurocognitive performance after cardiopulmonary bypass in rats
Received 7 October 2008; received in revised form 20 May 2009; accepted 20 June 2009. published online 30 July 2009.
Objective
Cerebral inflammatory reaction is discussed as a contributor to adverse cerebral outcome after cardiac surgery with cardiopulmonary bypass. This study was designed to determine the effect of cardiopulmonary bypass on both cerebral expression of tumor necrosis factor α and neurocognitive outcome in rats.
Methods
With institutional review board approval, 50 rats were randomly assigned to one of 3 groups: rats of the cardiopulmonary bypass group were subjected to 75 minutes of normothermic cardiopulmonary bypass. Sham-operated animals underwent identical preparation but were not connected to cardiopulmonary bypass, whereas rats of the control group were neither anesthetized nor cannulated. Ten rats per group survived 4 hours after cardiopulmonary bypass or the sham operation for immediate postoperative determination of tumor necrosis factor α–expressing cells (immunohistochemistry) and cerebral tumor necrosis factor α mRNA levels (polymerase chain reaction). The remaining animals survived 10 days for neurocognitive assessment by using the modified hole-board test and for analysis of cerebral tumor necrosis factor α activation in the late postoperative period.
Results
Expression of tumor necrosis factor α mRNA was increased 4 hours after cardiopulmonary bypass and the sham operation, with higher expression in the cardiopulmonary bypass group (χ2 [2] = 25.08, P < .001). Both experimental groups demonstrated larger numbers of tumor necrosis factor α–positive cells in the early and late postoperative periods (F [1] = 13.08, P ≤ .001) and an impaired neurocognitive performance on the first postoperative days compared with that seen in the control group (F [2, 24] = 4.26, P = .02).
Conclusions
Cerebral tumor necrosis factor α activation in both experimental groups during the early postoperative period was accompanied by transient neurocognitive impairment. Therefore cardiopulmonary bypass alone demonstrated no effect on cerebral inflammation and neurocognitive outcome.
ABSTRACT