Korean J Thorac Cardiovasc Surg.
2000 Mar;33(3):221-229.
Effect of Aprotinin on Changes in Plasma Thromboxane B2 and Endothelin-1
Concentratin after Extracorporeal Circulation
- Affiliations
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- 1Department of Thoracic and Cardiovascular Surgery, College of Medicine, University of Ulsan.
- 2Asan Institute for Life Sciences.
- 3Department of Biochemistry, College of Medicine, University of Ulsan.
- 4Department of Thoracic and Cardiovascular Surgery, College of Medicine, Seoul National University.
Abstract
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BACKGROUND: Thromboxane A2 and endothelin-1 are the potent vasoconstrictors affecting
pulmonary pathophysiology in response to whole body inflammatin following CPB. Aprotinin, as
an antiiflammatory agent, may decrease the release of such vasoactive substance from pulmonary
tissues, preventing pulmonary hypertension after cardiopulmonary bypass.
MATERIAL AND METHOD: Ten mongrel dogs(Bwt. ac. 20kg) were subjected to cardioupulmonary bypass
for 2 hours and postbypass pulmonary vascular resistance(0, 1, 2, 3 hours) were compared with
prebypass level. The dogs were divided into 2 groups; control group(n-5) and aprotinin
group(n=5). In the aprotinin group, aprotinin was administered as follows; 50,000 KIU/kg
mixed in pump priming solution, 50,000 KIU/kg prebypass intravenous infusion over 30 minutes,
10,000 KIU/kg/hour postbypass continuous infusion. Prebypass and postbypass 0, 1, 2, 3 hour
pulmonary vascular resistance were measured. At prebypass and postbypass 0, 90, 180 minutes,
blood samples were obtained from pulmonary arterial and left atrial catherers for the assay
of plasma thromboxane B2 a stable metabolite of thromboxane A2, and endothelin-1
concentrations.
RESULT: The ratios of pustbypass over prebypass pulmonary vascular at postbypass 0, 1, 2, 3
hours were 1.28+/-0.20, 1.82+/-0.23, 1.90+/-0.19, 2.14+/-0.18 in control group, 1.58+/-0.18,
1.73+/-0.01, 1.66+/-0.10, 1.50+/-0.08 in aprotinin group ; the ratios gradually increased in
control group while decreased or fluctuated after postbypass 1 hour in aprotinin group. There
was statistically significant difference between control group and aprotinin group at
postbypass 3 hours(P=0.014). Pulmonary arterial plasma concentration of thromboxane B2(pg/ml)
at prebypass, postbypass 0, 90, 180 minutes were 346.4+/-61.9, 529.3+/-197.6, 578.3+/-255.8,
493.3+/-171.3 in control group, 323.8+/-118.0, 422.6+/-75.6, 412.3+/-59.9, 394.5+/-154.0 in
aprotinin group. Left atrial concentrations were 339.3+/-89.2, 667.0+/-65.7, 731.2+/-192.7,
607.5+/-165.9 in control group, 330.0+/-111.2, 468.4+/-190.3, 425.4+/-193.6, 4.7.3+/-142.8 in
aprotinin group. These results showed decrement of pulmonary thromboxane A2 generation in
aprotinin group. Pulmonary arterial concentrations of endothelin-1(fmol/ml) at the same time
sequence were 7.84+/-0.31, 13.2+/-0.51, 15.0+/-1.22, 16.3+/-1.73 in control group, 7.76+/-0.12, 15.3+/-0.71, 22.6+/-6.62, 14.9+/-1.11 in aprotinin group. Left atrial concentrations were
7.61+/-17.2, 57.1+/-28.4, 18.9+/-18.2, 31.5+/-20.5 in control group, 5.61+/-7.61, 37.0+/-26.2,
28.6+/-21.7, 37.8+/-30.6 in aprotinin group. These results showed that aprotinin had no effect
on plasma endothelin-1 concentration after cardiopulmonary bypass.
CONCLUSIONS
Administration of aprotinin during cardiopulmonary bypass could attenuate the
increase in pulmonary vascular resistance after bypass. Inhibition of pulmonary thromboxane
A2 generation was thought to be one of the mechanism of this effect. Aprotinin had no effect
on postbypass endothelin-1 concentration.