Brain expression of inducible cyclooxygenase 2 messenger RNA in rats undergoing cardiopulmonary bypass.
BACKGROUND
We hypothesized that systemic proinflammatory cytokines or endotoxemia, or both, associated with cardiopulmonary bypass (CPB) would increase expression of inducible cyclooxygenase (COX-2) or inducible nitric oxide synthase (iNOS) messenger RNA (mRNA), or both, in brain.


METHODS
Isoflurane-anesthetized Sprague-Dawley rats were randomly selected for CPB (n = 6) or sham surgery (n = 6). All animals underwent tracheotomy and controlled ventilation, arterial and venous pressure monitoring, insertion of a jugular venous outflow catheter, insertion of a subclavian arterial inflow catheter, systemic anticoagulation (500 U/kg heparin) and, except during CPB, servoregulation of pericranial temperature at 37.5 degrees C. Animals selected for CPB underwent 1 h of CPB at 165 ml x kg(-1) x min(-1) (31.8 +/- 0.2 degrees C), whereas animals having sham surgery underwent no intervention during this interval. Thereafter, all animals were given protamine and remained anesthetized for 4 more h. Brain and liver COX-2 and iNOS mRNA expression were determined by a ribonuclease protection assay with ribosomal L32 mRNA as a loading control. Arterial blood was analyzed for interleukin 1beta, interleukin 6, and endotoxin concentrations.


RESULTS
Endotoxin concentrations did not increase above baseline values in either group. At 4 h after the CPB interval, interleukin 6 concentrations were significantly greater in CPB animals (101 +/- 45 pg/ml) versus sham animals (44 +/- 17 pg/ml) (P = 0.025). Brain COX-2 expression was significantly greater in CPB animals (0.36 +/- 0.11) versus shams (0.19 +/- 0.08) (P = 0.013). Brain COX-2 expression correlated with interleukin 6 concentration 4 h after CPB (r = 0.91; P = 5 x 10(-5)). In brain, iNOS mRNA was not detected in any animal. Cardiopulmonary bypass animals had only trace COX-2 and iNOS mRNA induction in liver.


CONCLUSIONS
Cardiopulmonary bypass was associated with increased systemic interleukin 6 concentrations and increased brain COX-2 expression.
Hindman
B J
BJ
Department of Anesthesia, University of Iowa, College of Medicine, Iowa City, USA. Brad-Hindman@uiowa.edu
Moore
S A
SA
Cutkomp
J
J
Smith
T
T
Ross-Barta
S E
SE
Dexter
F
F
Brian
J E
JE
D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation; D000818:Animals; D001921:Brain / Q000201:enzymology; D002315:Cardiopulmonary Bypass; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000096:biosynthesis*; D004731:Endotoxins / Q000494:pharmacology; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis*; D007530:Isoflurane; D008099:Liver / Q000201:enzymology; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D023282:Nuclease Protection Assays; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018685:Anesthetics, Inhalation; D016207:Cytokines; D004731:Endotoxins; D007527:Isoenzymes; D012333:RNA, Messenger; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D003576:Electron Transport Complex IV