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

Klinik für Anaesthesiologie, Technische Universität München, Klinikum rechts der Isar, München, Germany.
The Journal of thoracic and cardiovascular surgery (Impact Factor: 4.17). 07/2009; 138(4):1002-7. DOI: 10.1016/j.jtcvs.2009.06.022
Source: PubMed

ABSTRACT 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.
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.
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 < or = .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).
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.

9 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neurologic and neurocognitive complications after cardiac surgery have been reported repeatedly. To better understand its etiology and design protective strategies, small animal models have been developed. This study describes the development of a survival rat cardiopulmonary bypass (CPB) model, along with the introduction of an appropriately sized oxygenator. This model led the way for even more complicated models with CPB, facilitating full cardiac arrest with anterograde cardioplegia administration, air embolization, and deep hypothermic circulatory arrest. In addition, the results of several of those rat CPB studies are summarized and their preclinical relevance is pointed out.
    Seminars in Cardiothoracic and Vascular Anesthesia 06/2010; 14(2):136-40. DOI:10.1177/1089253210370491
  • [Show abstract] [Hide abstract]
    ABSTRACT: Moxifloxacin reduces infectious complications after cerebral damage, such as ischemia and stroke. This study investigated whether moxifloxacin treatment influences cerebral inflammation and improves cognitive outcome after cardiopulmonary bypass with deep hypothermic circulatory arrest in rats. Rats were randomly assigned to deep hypothermic circulatory arrest (n = 40), sham operation (n = 40), and untreated control (n = 20) groups. Deep hypothermic circulatory arrest and sham groups were equally subdivided into moxifloxacin and placebo subgroups, receiving 6 × 100 mg/kg moxifloxacin or saline solution every 2 hours intraperitoneally. Hippocampal tumor necrosis factor α, nuclear factor κB, cyclooxygenase 2, and macrophages were assessed immunohistochemically. Histologic outcome was determined with hematoxylin and eosin. Neurologic outcome was assessed preoperatively and postoperatively. Cognitive performance was tested with the modified hole board test for 14 postoperative days. On postoperative day 14, deep hypothermic circulatory arrest moxifloxacin group was lower than deep hypothermic circulatory arrest placebo group in hippocampal neurons positive for tumor necrosis factor α (1.33, 0.73-2.37, vs 4.10, 2.42-18.67), nuclear factor κB (3.03, 1.33-5.20, vs 9.32, 2.53-24.14), and cyclooxygenase 2 (3.16, 0.68-6.04, vs 8.07, 3.27-19.91) and also had fewer macrophages than all other groups (72, 60-90, vs deep hypothermic circulatory arrest placebo 128, 76-203, sham moxifloxacin 89, 48-96, and sham placebo 81, 47-87). On postoperative day 14, both deep hypothermic circulatory arrest groups showed impaired motor, cognitive, and histologic outcomes relative to sham-operated groups, with no difference between deep hypothermic circulatory arrest subgroups. Moxifloxacin transiently reduces cerebral inflammatory reaction, but without impact on neurologic function, histologic outcome, or long-term cognitive performance.
    The Journal of thoracic and cardiovascular surgery 03/2011; 141(3):796-802. DOI:10.1016/j.jtcvs.2010.04.017 · 4.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autologous blood transfusion (ABT), for example, by means of cell saver equipment, is used to reduce the need for allogenic blood transfusion in patients with high perioperative blood loss. This study investigated the effect of blood/extracorporal surface interaction during withdrawal and retransfusion of shed autologous blood on cerebral inflammation in rats. Rats subjected to hypotension with cerebral ischemia served as positive controls. Eighty-eight male Sprague-Dawley rats were anesthetized with sevoflurane, instrumented, and randomly assigned to the following groups: sham-operation (SHAM), autologous blood withdrawal/transfusion only (ABT), or bilateral carotid artery occlusion and autologous blood withdrawal/transfusion (BCAO/ABT). Inflammatory gene expression was investigated with real-time RT-polymerase chain reaction at 6, 12, and 24 hours after SHAM, ABT, or BCAO/ABT in brain hippocampal tissue. Naive rats were investigated as reference. ABT alone had no impact on hippocampal inflammatory gene expression, whereas after BCAO/ABT tumor necrosis factor-alpha (10.7 fold at 24 h), interleukin-1β (2.1 fold at 6 h), interleukin-6 (35.7 fold at 24 h), COX-2 (9.3 fold at 6 h), and inducible nitric oxide synthase (3.4 fold at 24 h) increased compared with SHAM. ABT by itself did not provoke an inflammatory reaction in the healthy brain. However, in combination with cerebral ischemia the induction of a broad spectrum of inflammatory parameters indicates an inflammatory reaction of the hippocampus beginning after 6 hours and being most pronounced after 24 hours. Therefore, this study shows that cerebral inflammation is not induced by ABT after contact with extracorporal surfaces in rats.
    Journal of neurosurgical anesthesiology 07/2011; 23(3):215-21. DOI:10.1097/ANA.0b013e31821a1150 · 2.99 Impact Factor
Show more