Dose-dependent effect of aprotinin on aggravated pro-inflammatory cytokines in patients with pulmonary hypertension following cardiopulmonary bypass.
BACKGROUND
To investigate the dose dependent effect of aprotinin on aggravated pro-inflammatory cytokines in patients with pulmonary hypertension (PH) after cardiopulmonary bypass (CPB).


METHODS
Thirty-two patients with pulmonary arterial pressure (PAP) above 60 mmHg were recruited. They were assigned randomly to control (Group A, n = 8), and treated groups (Group B with aprotinin = 0.5 x 10(5) KIU/Kg, and Group C with aprotinin = 1.0 x 10(5) KIU/Kg, n = 12 each group). Blood samples were collected at various intervals of time and analyzed, from "0" hour (before CPB as baseline), at the completion of CPB, 4 hours and 24 hours after CPB, to measure the concentrations of interleukin 1beta (IL-1beta), interleukin-8 (IL-8), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha).


RESULTS
All the biomarkers significantly increased after CPB. There was no significant difference in cytokine levels between Group A and group B after CPB. But IL-1beta, IL-8 and TNF-alpha of Group C were not only significantly lower than Group A (p < 0.05), but also lower than Group B at various time points after CPB (p < 0.05). IL-10 of group C was significantly higher than Group A and Group B after CPB (p < 0.05).


CONCLUSIONS
High dose aprotinin can suppress the release of pro-inflammatory cytokines IL-1beta, IL-8 and TNF-alpha, and enhance the release of IL-10 in patients with PH after CPB. For patients having PH, there exists a simple and potential way to reduce the inflammatory response by applying high dose aprotinin.
Lei
Ye
Y
Department of Surgery, National University Hospital, National University of Singapore, 117597 Singapore. yeleislp@yahoo.com
Haider
Husnain Kh
HKh
Chusnsheng
Wang
W
Zhiqiang
Cheng
C
Hao
Chen
C
Kejian
Hu
H
Qiang
Zhao
Z
D000368:Aged; D007611:Aprotinin / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D015415:Biomarkers; D016207:Cytokines; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin