von Willebrand factor and urinary albumin excretion are possible indicators of endothelial dysfunction in cardiopulmonary bypass.
OBJECTIVE
Experimental evidence suggests that cardiopulmonary bypass (CPB) associated inflammatory response leads to endothelial injury and increased permeability, but this has been difficult to show clinically. We have investigated the use of von Willebrand factor (vWF), and urinary albumin excretion, as measured by the urinary albumin creatinine ratio (ACR), to demonstrate this.


METHODS
A total of 23 patients undergoing elective coronary artery bypass grafting were studied. Complement fragment C3a, leukotrienne B4 (LTB4), interleukin 6 (IL6), neutrophil elastase, vWF and ACR were measured on anaesthetic induction (baseline), 20 min after starting CPB, 5 min after cross-clamp removal, 5 min, 2, 6 and 24 h after termination of CPB. Anaesthetic, CPB and myocardial protection techniques were standardised. ANOVA was performed by using the distribution free Friedman test for each measured parameter. When significance differences were found (P < 0.05), post hoc analysis with Wilcoxon signed rank test was used for comparison of each time point with the base line level and differences were only accepted as significant following the Bonferroni correction (P < 0.008). Summary measures of peak versus peak and area under the cure were also analysed for ACR with vWF.


RESULTS
Peak vs. baseline levels for C3a were 4.9 vs. 2.1 microg/ml (P < 0.0001), LTB4 was 800 vs. 20 pg/ml (P < 0.0001), neutrophil elastase was 250 vs. 115 ng/ml (P < 0.001), IL6 was 620 vs. 1.4 pg/ml (P < 0.0001), vWF was 2.2 vs. 1.3 IU/ml (P < 0.0001) and ACR was 17.6 vs. 2.0 mg/mmol (P < 0.0001). C3a, LTB4 and ACR peaked during the operation. Neutrophil elastase peaked at 2 h following CPB. IL6 and vWF peaked at 6 h following CPB. The correlation coefficient between vWF and ACR following peak versus peak analysis was 0.48 (P = 0.035), and area under the curve analysis was 0.6 (P < 0.01).


CONCLUSIONS
These results demonstrate that endothelial permeability and injury, as measured by urinary albumin excretion and vWF, respectively, are related and the use of these easily detectable and sensitive biochemical markers warrants further investigation.
Tsang
G M
GM
Cardiothoracic Surgery Unit, University Hospital, Edgbaston, Birmingham, UK. g.m.k.tsang@bham.ac.uk
Allen
S
S
Pagano
D
D
Wong
C
C
Graham
T R
TR
Bonser
R S
RS
D000368:Aged; D000419:Albuminuria / Q000209:etiology* / Q000503:physiopathology; D000787:Angina Pectoris / Q000601:surgery; D015415:Biomarkers / Q000652:urine; D002199:Capillary Permeability; D002315:Cardiopulmonary Bypass; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000652:urine; D007387:Internal Mammary-Coronary Artery Anastomosis; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000652:urine; D014841:von Willebrand Factor / Q000652:urine*
D015415:Biomarkers; D015850:Interleukin-6; D014841:von Willebrand Factor