title: Cardiopulmonary bypass and long-term neurocognitive dysfunction in the rat.
abstract: Neurologic and neurocognitive complications after cardiac surgery with cardiopulmonary bypass (CPB) have been reported repeatedly. To better understand its etiology and design protective strategies, an appropriate animal model may prove useful. Although impaired short-term neurocognitive function has been recently demonstrated after CPB in rats, the demonstration of persistent long-term neurocognitive changes would be more relevant from a clinical perspective. We hypothesized that CPB results in long-term impairment of neurocognitive performance in rats. Male rats were exposed to either 60 min of normothermic non-pulsatile CPB, using a roller-pump and a neonatal membrane oxygenator, or to cannulation only (sham animals). Long-term neurocognitive function was assessed at 4 to 7 weeks after CPB (Can test), and again after 12 weeks (Morris water maze) in both operated groups and in a non-operated control group, followed by histologic evaluation of the hippocampus. In separate groups of CPB and sham animals, we also measured TNF-alpha and IL-6 in plasma. There were no significant differences in long-term neurocognitive performance or histological outcome between the three groups. Cytokine patterns were also similar in both operated groups. We conclude that CPB did not appear to cause long-term neurocognitive dysfunction in this model of CPB in young healthy rats. The lack of long-term deficits may be due to the absence of clinically important etiologic factors such as atheromatous and gaseous embolization in this model. Similar cytokine patterns in both operated groups suggest that surgical trauma rather than exposure of blood to extra-corporeal circuit was probably responsible for the inflammatory response.
authors.affiliation: Division of Perioperative Care and Emergency Medicine, University Medical Center Utrecht, PO Box 85500, mail stop Q04.2.313, 3508 GA Utrecht, The Netherlands. S.Dieleman@UMCUtrecht.nl
authors.forename: Jan M
authors.initials: JM
authors.lastname: Dieleman
authors.forename: Fellery
authors.initials: F
authors.lastname: de Lange
authors.forename: Ralph J F
authors.initials: RJ
authors.lastname: Houston
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Biessels
authors.forename: P R
authors.initials: PR
authors.lastname: Bär
authors.forename: G Burkhard
authors.initials: GB
authors.lastname: Mackensen
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Grocott
authors.forename: Cor J
authors.initials: CJ
authors.lastname: Kalkman
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D006624:Hippocampus / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D009422:Nervous System Diseases / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012107:Research Design; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha