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J Thorac Cardiovasc Surg 2009;138:1002-1007
© 2009 The American Association for Thoracic Surgery

Evolving Technology/Basic Science

Cerebral tumor necrosis factor {alpha} expression and long-term neurocognitive performance after cardiopulmonary bypass in rats

Bettina Jungwirth, MDa,*, Kristine Kellermann, DVMa, Ma Qing, MDb, G. Burkhard Mackensen, MDb, Manfred Blobner, MDa, Eberhard F. Kochs, MDa

a Klinik für Anaesthesiologie, Technische Universität München, Klinikum rechts der Isar, München, Germany
b Department of Anesthesiology, Duke University Medical Center, Durham, NC

Received for publication October 7, 2008; revisions received May 20, 2009; accepted for publication June 20, 2009.

* Address for reprints: Bettina Jungwirth, MD, Klinik für Anaesthesiologie, Technische Universität München, Klinikum rechts der Isar, Ismaningerstrasse 22, 81675 München, Germany. (Email: b.jungwirth{at}lrz.tum.de).

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 {alpha} 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 {alpha}–expressing cells (immunohistochemistry) and cerebral tumor necrosis factor {alpha} 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 {alpha} activation in the late postoperative period.

Results: Expression of tumor necrosis factor {alpha} mRNA was increased 4 hours after cardiopulmonary bypass and the sham operation, with higher expression in the cardiopulmonary bypass group ({chi}2 [2] = 25.08, P < .001). Both experimental groups demonstrated larger numbers of tumor necrosis factor {alpha}–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 {alpha} 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.

Abbreviations and Acronyms CPB = cardiopulmonary bypass; MAP = mean arterial pressure






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