Effect of haemodynamic changes on epithelium-related intestinal injury in off-pump coronary surgery.

OBJECTIVES: Intestinal injury is thought to play a central role in the occurrence of multiorgan dysfunction after on-pump coronary surgery. Clinical benefits of off-pump revascularisation remain, however, controversial. MATERIAL AND METHODS: Hepatic enzymes and plasmatic IL-6, IL-8 and intestinal-type fatty acid binding protein (I-FABP) were determined in 20 patients (age 65-75) undergoing either on-pump (n = 10) or off-pump (n = 10) coronary surgery. Haemodynamic and biochemical parameters, catecholamine and volume therapy were monitored. RESULTS: Central venous pressure (CVP) was significantly higher in the off-pump group during and 12h after operation (9.5 ± 1.35 vs. 6.21 ± 0.63 mmH2O, p = 0.012). Higher GGT and GLDH levels occurred in the off-pump group and correlated with the elevated I-FABP levels at 24h (935.8 ± 83.7 vs. 370.4 ± 67.7 pg/mL, p<0.001). CVP correlated with I-FABP peak values (Pearson's coefficient 0.852). IL-6 and IL-8 were released to a lower extent in the off-pump group compared to on pump (p<0.05) at 24h (139.3 ± 27.7 vs. 279.4 ± 56.2 and 15.3 ± 7.4 vs. 38.5 ± 13.8 pg/mL) and at 72 h post-operatively (4.5 ± 2.1 vs. 30.1 ± 12.1 and 7.8 ± 1.2 vs. 17.1 ± 5.2 pg/mL). CONCLUSIONS: While inflammatory activation is reduced with CPB avoidance, elevated CVP during off-pump surgery is followed by temporary postoperative enterocyte damage that may threaten the normal function of the gastrointestinal system and lead - in certain groups of high risk patients--to irrecoverable injury.

Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits.

N-methyl-D-aspartate receptor (NMDAR) composition in granule cells changes characteristically during cerebellar development. To analyze the importance of NR2B replacement by NR2C and NR2A subunits until the end of the first month of age, we generated mice with lasting NR2B expression but deficiency for NR2C (NR2C-2B mice). Mutant phenotype was different from NR2C knock-out mice as loss of granule cells and morphological changes in NR2C/2B cerebellar architecture were already evident from the second postnatal week. Increased NR2B subunit levels led also to a gradual down-regulation of cerebellar NR2A levels, preceding the development of motor impairment in adult animals. Therefore, cerebellar NR2A is important for proper motor coordination and cannot be replaced by long-term expression of NR2B. Consequently, the physiological exchange of NMDA receptor subunits during cerebellar granule cell maturation is important for accurate postnatal development and function.