Effect of Aprotinin on Changes in Plasma Thromboxane B2 and Endothelin-1 Concentratin after Extracorporeal Circulation / 대한흉부외과학회지

ABSTRACT

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.