title: Exacerbation of acute pancreatitis in the presence of chronic liver injury in rats, with special reference to therapeutic efficacy of prostaglandin E1.
abstract: The pathophysiology of acute pancreatitis accompanied by chronic liver injury, and the therapeutic efficacy of prostaglandin (PG)E1 were studied experimentally in rats. Chronic liver injury was produced by subcutaneous administration of CCl4. Acute pancreatitis was induced by the closed duodenal loop (CDL) method, immediately after which PGE1 (60 ng/kg/min) was infused intravenously via the jugular vein. Serum levels of amylase, alpha2-macroglobulin-trypsin complex (alpha2M-TRY), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were determined before and at 3 and 6 h after the onset of acute pancreatitis. Rats without administration of CCl4 served as controls. Serum amylase levels were lower in the liver injury (LI) group than in the normal liver (NL) group at 3 and 6 h. PGE1 had no effect on amylase levels in either group. Serum alpha2M-TRY levels were similar in the two groups at 3 h, but significantly higher in LI than in NL at 6 h. PGE1 tended to decrease alpha2M-TRY levels only in LI. Serum CRP levels were significantly more elevated in LI than in NL at 0, 3, and 6 h. PGE1 decreased CRP levels only in LI. Serum TNF-alpha concentrations were higher in LI, especially at 6 h. PGE1 reduced TNF-alpha levels in LI. Pancreatitis severity scores were significantly higher in LI. PGE1 significantly decreased the severity scores only in LI. Fat necrosis scores were significantly lower in LI. Histologically, interstitial edema was much more prominent in NL than in LI, whereas interstitial hemorrhage was more severe in LI at 3 and 6 h. PGE1 lessened the hemorrhage in LI. The extent of both vacuolization and necrosis of acinar cells was similar for both groups and tended to be improved by PGE1. It is concluded that acute pancreatitis becomes much more serious in the presence of chronic liver injury, and that PGE1 can ameliorate the exacerbated lesions, probably by improvements in blood flow through the pancreatic tissue.
authors.affiliation: Department of Surgery, National Sendai Hospital, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Imamura
authors.forename: Y
authors.initials: Y
authors.lastname: Mikami
authors.forename: H
authors.initials: H
authors.lastname: Yamauchi
mesh_terms: D000208:Acute Disease; D000527:Alprostadil / Q000008:administration & dosage / Q000627:therapeutic use*; D000681:Amylases / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity; D018450:Disease Progression; D007262:Infusions, Intravenous; D007601:Jugular Veins; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010195:Pancreatitis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; C028939:alpha-2-macroglobulin-trypsin complex; D000511:alpha-Macroglobulins; D002251:Carbon Tetrachloride; D000681:Amylases; D014357:Trypsin; D000527:Alprostadil