Brain expression of inducible cyclooxygenase 2 messenger RNA in rats undergoing cardiopulmonary bypass

Background: We hypothesized that systemic proinflammatory cytokines or endo toxemia, or both, associated with cardiopulmonary bypass (CPB) would increa se 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 tinder-went tracheoto my and controlled ventilation, arterial and venous pressure monitoring, ins ertion of a jugular venous outflow catheter, insertion of a subclavian arte rial inflow catheter, systemic anticoagulation (500 U/kg heparin) and, exce pt during CPB, servoregulation of pericranial temperature at 37.5 degreesC. Animals selected for CPB underwent I h of CPB at 165 nil . kg(-1) . min(-1 ) (31.8 +/- 0.21 degreesC), whereas animals having sham surgery underwent n o intervention during this Interval. Thereafter, all animals were given pro tamine and remained anesthetized for 4 more h. Brain and liver COX-2 and iN OS mRNA expression were determined by a ribonuclease protection assay with ribosomal L32 mRNA as a loading control. Arterial blood was analyzed for in terleukin 1 beta, 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 an imals (44 +/- 17 pg/ml) (P = 0.025). Brain COX-2 expression was significant ly 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 dete cted 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.