Effects of urinary protease inhibitor on inflammatory response during on-pump coronary revascularisation. Effect of ulinastatin on inflammatory response.
OBJECTIVE
Cardiac surgery in patients undergoing cardiopulmonary bypass (CPB) provokes a vigorous inflammatory response with substantial clinical implications. Once the inflammatory response is triggered by CPB, leukocytes and platelets are activated by multiple stimuli. The administration of a urinary trypsin inhibitor (ulinastatin) during CPB is hypothesized to reduce cytokine release and platelet activation and to decrease pulmonary injury. We performed a prospective randomized study to investigate the influence of high-dose ulinastatin on cytokines and platelet activation and on respiratory function during and after CPB.


METHODS
In this pilot, prospective, randomized and double-blinded study, 30 first-time three-vessel coronary artery disease (CAD) patients undergoing coronary artery bypass graft (CABG) were randomly divided into 2 groups: U group (n=15) received a total dose of 1000000 U ulinastatin and C group (n=15) received placebo. Blood samples were withdrawn from the central vein to measure polymorphonuclear neutrophil elastase (PMNE), tumour necrosis factor-alpha (TNF-a), interleukin-6 (IL-6) and interleukin-8 (IL-8), before induction, 30 min following clamping (T2), reperfusion 3 h (T3), reperfusion 6 h (T4) and reperfusion 12 h (T5). Whole blood samples were taken for CD62P immediately before induction (as baseline), at the end of CPB (before protamine administration), 1 h after heparin neutralization by protamine and 24 h after the operation. In addition, alveolo-arterial oxygen difference (A-aDO(2)) in pulmonary gas exchange function was calculated by obtaining arterial blood gas samples before and after CPB.


RESULTS
There were no differences in preoperative parameters between the groups. After CPB, the levels of PMNE, TNF-alfa, IL-6 and IL-8 increased in both groups over baseline values (P<0.01). The levels of PMNE, TNF-alfa, IL-6 and IL-8 in U group were significantly lower than those in C group (P<0.05). No significant differences in CD62p expression between the 2 groups during CPB were found. A-aDO(2) in U group significantly decreased compared with C group (P<0.05) and the duration of mechanical ventilation was shorter than C group (P<0.05).


CONCLUSIONS
Results suggest that ulinastatin may inhibit proinflammatory cytokine (PMNE, TNF-alfa, IL-6 and IL-8) release, reduce reperfusion lung injury and preserve pulmonary function but it fails to inhibit platelet activation and to prevent blood loss during CPB.
Bingyang
J
J
Department of Cardiopulmonary Bypass, Cardiovascular Institute and Fuwai Hospital, PUMC & CAMS, Beijing, China. bingyangji@psu.edu
Jinping
L
L
Mingzheng
L
L
Guyan
W
W
Zhengyi
F
F
D000368:Aged; D001784:Blood Gas Analysis; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000097:blood* / Q000601:surgery; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D019272:Leukocyte Elastase / Q000097:blood; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010865:Pilot Projects; D015539:Platelet Activation / Q000187:drug effects*; D011446:Prospective Studies; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D016207:Cytokines; D006023:Glycoproteins; D018836:Inflammation Mediators; D019007:P-Selectin; D014361:Trypsin Inhibitors; D019272:Leukocyte Elastase; C028665:urinastatin