Cerebral tumor necrosis factor alpha expression and long-term neurocognitive performance after cardiopulmonary bypass in rats.
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)  = 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  = 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.
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ABSTRACT: OBJECTIVE: Postoperative cognitive dysfunction occurs frequently after cardiac surgeries with cardiopulmonary bypass (CPB). Available data from rat CPB models are conflicting. However, none of them was designed to investigate the role of isoflurane (the main anesthetic in all of these studies) in the neurocognitive dysfunction after CPB. Isoflurane has documented neuroprotective effects so the present authors hypothesized that isoflurane prevents the neurocognitive dysfunction in rats after CPB. DESIGN: A prospective, interventional study. SETTING: A university research laboratory. PARTICIPANTS: Male Sprague-Dawley rats. INTERVENTIONS: Male Sprague-Dawley rats were divided into 5 groups: the isoflurane CPB group, the animals were anesthetized with isoflurane and underwent 60 minutes of normothermic CPB; the chloral hydrate CPB group, the animals were anesthetized with chloral hydrate and underwent 60 minutes of normothermic CPB; the isoflurane sham group, the animals were subjected only to cannulation and the same duration of anesthesia but no CPB; the chloral hydrate sham group, the animals received only cannulation and the same duration of anesthesia but no CPB; and the naive group, the animals received no treatment. The neurocognitive function of all rats was measured on days 4 to 6 (short-term) and 31 to 33 after CPB (long-term). After the behavior tests, the animals were sacrificed, and the brain was harvested for the measurement of acetylcholinesterase (AChE) and choline acetyltransferase protein levels. MEASUREMENTS AND MAIN RESULTS: Short-term (days 4-6 after CPB) learning and memory were impaired after CPB when the animals were anesthetized with chloral hydrate. When isoflurane was used, the learning and memory did not change after CPB. No long-term (days 31-33 after CPB) neurocognitive changes were found after CPB. AChE decreased significantly after isoflurane anesthesia regardless of whether CPB was performed. CONCLUSIONS: Isoflurane prevented the neurocognitive dysfunction induced by CPB, which might involve the cerebral cholinergic system.Journal of cardiothoracic and vascular anesthesia 11/2012; · 1.06 Impact Factor
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ABSTRACT: Postoperative cognitive dysfunction is receiving increasing attention, particularly as it mainly affects the (growing) elderly population. Until recently, cognitive deficits after cardiac surgery were thought to be caused by physiological disturbances associated with the cardiopulmonary bypass technique. Although the technique of 'off-pump' coronary revascularisation may potentially be associated with improved outcome, long-term follow-up studies have failed to demonstrate a significant reduction in the incidence of postoperative cognitive dysfunction. The focus of research is thus shifting from cardiopulmonary bypass to other factors common to both techniques, such as surgery, anaesthesia and patient-related predisposing factors. Priming of the immune system by ageing and atherosclerosis may result in an exaggerated systemic and cerebral inflammatory response to cardiac surgery and anaesthesia, causing neuronal loss or dysfunction resulting in cognitive dysfunction. We briefly discuss the evidence for cardiopulmonary bypass-related neuronal injuries in adult cardiac surgery patients, and review the evidence that immune priming is a key factor in the pathogenesis of cognitive dysfunction after cardiac surgery.Anaesthesia 03/2012; 67(3):280-93. · 3.49 Impact Factor
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ABSTRACT: PURPOSE OF REVIEW: To summarize recent studies of neurocognitive dysfunction after cardiac surgery, as well as to outline efforts and approaches toward advancing the field. RECENT FINDINGS: Observational studies have improved our understanding of the incidence and the trajectory of cognitive decline after cardiac surgery; however, the magnitude of this neurocognitive change remains controversial because of the inconsistent definitions and the lack of a gold-standard diagnostic modality. Nonetheless, physicians commonly see patients with functional and cognitive impairments after cardiac surgery, which utilize healthcare resources and impact quality of life. Novel approaches have utilized advanced neuroimaging techniques as well as innovative monitoring modalities to improve the efficiency of neuroprotective strategies during cardiac surgery. SUMMARY: Adverse cognitive and neurologic outcomes following cardiac surgery range from discrete neurocognitive deficits to severe neurologic injury such as stroke and even death. The elderly are at higher risk of suffering these outcomes and the public health dimension of this problem is expected to accelerate. Future studies should combine advanced neuroimaging with genomic, transcriptional, proteomic, and metabolomic profiling to improve our understanding of the pathophysiologic mechanisms and optimize the diagnosis, prevention, and treatment of neurocognitive injury.Current opinion in anaesthesiology 12/2012;