[Mechanisms of organ failure following cardiopulmonary bypass--preventive effects of ulinastatin].
The causes of organ failure following cardiopulmonary bypass (CPB) were multi-factorial. Damage was initiated by elastase which was released from activated granulocytes under conditions of significant reduction in the protease inhibitor level (p less than 0.01). Platelet aggregation, initiated by the CPB, altered the eicosanoid metabolism. As a result, the level of thromboxane A2 increased and became dominant in relation to prostaglandin I2. The increase in endothelin excretion observed during and after the CPB induced a further vasoconstrictive response in the microvasculature and accelerated ischemic cellular damage. Upon completion of the CPB, the elevation of the lysosomal enzyme beta-glucuronidase was influenced by the concentration of elastase (r = 0.78). The endothelin level correlated slightly with the elastase level (r = 0.4) during the CPB. This might indicate that there was an interaction between the activated granulocytes and endothelin production. The increase in the alveolar-arterial oxygen tension difference (Aa-DO2) only correlated with the elastase concentration (r = 0.55). Renal damage, which was detected by an increase in renal tubular enzymes (N-acetyl-beta-D-glucosaminidase and gamma-glutamyltranspeptidase), was affected by endothelin (r = 0.68, 0.58) and elastase (r = 0.61, 0.51) respectively, but not by thromboxane B2. Even after the CPB, damage was thought to be perpetuated by the continuous elevation of elastase and endothelin. Since thromboxane A2 dominance subsided immediately after the cardiopulmonary bypass, the effect of thromboxane A2 on the development of organ failure was possibly only influential during the CPB. The cardiac index demonstrated a negative correlation with endothelin (r = -0.69) and a positive correlation with the ratio of TxB2/PGF1 (r = 0.51).(ABSTRACT TRUNCATED AT 250 WORDS)
Hashimoto
K
K
Department of Cardiovascular Surgery, Jikei University School of Medicine, Tokyo, Japan.
Horikoshi
S
S
Miyamoto
H
H
Okuyama
H
H
Suzuki
K
K
Matsui
M
M
Arai
T
T
Kurosawa
H
H
D000328:Adult; D000368:Aged; D002315:Cardiopulmonary Bypass; D016232:Endothelins / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000627:therapeutic use*; D006349:Heart Valve Diseases / Q000378:metabolism / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D013928:Thromboxane A2 / Q000378:metabolism
D016232:Endothelins; D006023:Glycoproteins; D011480:Protease Inhibitors; D013928:Thromboxane A2; C028665:urinastatin