Genetic predisposition in patients undergoing cardiopulmonary bypass surgery is associated with an increase of inflammatory cytokines.
OBJECTIVE
Cardiopulmonary bypass (CPB) surgery induces a transient rise in pro-inflammatory cytokines typically released by activated monocytes. The E4 variant of apolipoprotein E is a recognized risk factor for atherosclerosis. It has recently been shown that apolipoprotein E affects monocyte functions in vitro and leads to higher levels of median lipoprotein (a) in humans. The aim of the study is to investigate if the E4 genetic variant of apolipoprotein E affects cytokine release after CPB surgery.


METHODS
22 patients were operated on with standard coronary artery bypass grafting. Concentrations of interleukin 8 (IL-8) and tumor necrosis factor (TNF-alpha) were measured by automated Immulite immunoassay at regular intervals within 48 h after surgery. Total apparent cytokine outputs were calculated as area under the curve. Results are expressed as mean+/-standard deviation and compared by unpaired t-test.


RESULTS
In the presented patient population 6 (27%) carried the E4 allele. Sixteen (63%) showed no E4 allele. Mean cross clamp time (CCT) was 56.2+/-13.5 min versus 55.7+/-12.1 min and CPB time was 91.8+/-17.5 versus 93.5+/-15.7 min. No statistical difference between E4-carriers and E4 non-carriers regarding CCT and CPB was observed. The total amount of IL-8 and TNF-alpha was higher in patients carrying the E4 genetic variant of apolipoprotein E in comparison to E4 non-carriers (P<0.08, P<0.039).


CONCLUSIONS
The presence of the E4 allele is associated with increased release of IL-8 and TNF-alpha after CBP surgery. The preoperative determination of E4 in patients undergoing cardiac surgery may lead to additional perioperative measures for the treatment of an increased systemic inflammatory response.
Drabe
N
N
Clinic for Cardiovascular Surgery, University Hospital Zürich, Zürich, Switzerland.
Zünd
G
G
Grünenfelder
J
J
Sprenger
M
M
Hoerstrup
S P
SP
Bestmann
L
L
Maly
F E
FE
Turina
M
M
D000368:Aged; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002315:Cardiopulmonary Bypass; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D018836:Inflammation Mediators; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha