Protective effect of aprotinin on ischemic hepatocellular damage.
During hepatic resection, occlusion of the hepatoduodenal ligament has been frequently applied to prevent intraoperative bleeding. To reduce hepatocellular ischemic damage in this procedure, we pretreated animals with Aprotinin. Three hours after an intravenous injection of 40,000 KIU Aprotinin in SD rats, we occluded the afferent hepatic vessels for 50-min and 60-min periods. 92% of occluded animals could sustain life after 60 min. Without premedication only 17 of 25 animals (68%) survived the 50-min occlusion, and 18 of 32 (56%) the 60-min occlusion. Biochemical analysis of sera was carried out 12 hr after a 40- and 60-min occlusion of the hepatoduodenal ligament with Aprotinin pretreatment. Furthermore we induced compensatory cirrhosis by application of CCL4 and biochemical analysis of sera was carried out after a 30-min occlusion. The elevation of SGOT and SGPT values was drastically reduced in the animals with Aprotinin medication in comparison with those without treatment. These observations suggest the highly protective effect of Aprotinin in the case of warm ischemic hepatic damage, especially in the cirrhotic liver. After pretreatment of LEW rats with Aprotinin (40,000 KIU i.v.), we perfused the livers with chilled Ringer solution containing 40,000 KIU Aprotinin/20 ml. We transplanted the livers orthotopically into LEW rats. With the application of Aprotinin liver preservation time increased to 10-15 hr. However, without Aprotinin the livers could be successfully preserved for only 4-6 hr. Our results indicated that premedication with high doses of Aprotinin provided highly protective effects against warm and cold ischemic damage of the liver.
Lie
T S
TS
Department of Surgery, University of Bonn, Federal Republic of Germany.
Seger
R
R
Hong
G S
GS
Preissinger
H
H
Ogawa
K
K
D000818:Animals; D007611:Aprotinin / Q000627:therapeutic use*; D007511:Ischemia / Q000628:therapy*; D008099:Liver / Q000098:blood supply / Q000601:surgery*; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology / Q000601:surgery; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007611:Aprotinin