Effects of ulinastatin treatment on the cardiopulmonary bypass-induced hemodynamic instability and pulmonary dysfunction.
OBJECTIVE
To examine the association between decreased release of proinflammatory cytokines in response to urinary trypsin inhibitor pretreatment and decreased myocardial and lung injury after cardiopulmonary bypass.


METHODS
A prospective, randomized, double-blind study.


METHODS
University hospital.


METHODS
Thirty patients on cardiopulmonary bypass undergoing coronary artery bypass grafting.


METHODS
Patients received 5000 units/kg intravenous urinary trypsin inhibitor (n = 15) or 0.9% saline (control, n = 15) immediately before aortic cannulation for cardiopulmonary bypass.


RESULTS
Neutrophil elastase, tumor necrosis factor-alpha, interleukin-6, and interleukin-8 were measured after intubation (T1), immediately before aortic cannulation (T2), after separation from cardiopulmonary bypass (T3), at the end of surgery (T4), and on postoperative days 1 (T5), 3 (T6), and 5 (T7). Simultaneous hematocrit values were obtained at all sample times. Isoenzyme of creatine kinase with muscle and brain subunits, troponin-T, and myosin light chain I were also measured. Various hemodynamic and pulmonary data were obtained perioperatively. Levels of neutrophil elastase and cytokines were corrected for hemodilution. Interleukin-6 and interleukin-8 levels were lower at T3 and T4 in the urinary trypsin inhibitor group than in the control group. Stroke volume index was significantly decreased in the control group at T3, and statistical difference was found between groups at T3 (p < .01). Respiratory index and intrapulmonary shunt were significantly higher in the control group than in the urinary trypsin inhibitor group at T3. Changes in respiratory index and intrapulmonary shunt correlated with interleukin-8 levels at T3 (r = .52, p < 00001; r = .37, p < 0001, respectively) and T4 (r = .44, p < .001; r = .24, p < .05, respectively). Neutrophil elastase levels and cardiac marker responses to coronary artery bypass grafting surgery were similar in both groups.


CONCLUSIONS
Prepump administration of urinary trypsin inhibitor attenuates the elevation of interleukin-6 and interleukin-8 release immediately after cardiopulmonary bypass.
Department of Anesthesiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. n-kazu@nms.ac.jp
Kazuhiro
K
Nakanishi
Shinhiro
S
Takeda
Atsuhiro
A
Sakamoto
Akira
A
Kitamura
D000704:Analysis of Variance; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D001026:Coronary Artery Bypass; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D019272:Leukocyte Elastase / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000517:prevention & control*; D020107:Troponin T / Q000097:blood / Q000187:drug effects; D014361:Trypsin Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D016207:Cytokines; D006023:Glycoproteins; D020107:Troponin T; D014361:Trypsin Inhibitors; D019272:Leukocyte Elastase; C028665:urinastatin