Etiology of cecal and hepatic lesions in mice after administration of gas-carrier contrast agents used in ultrasound imaging.
The aim of the study was to investigate the etiology of cecal and hepatic lesions in mice and rats after intravenous administration of gas-carrier contrast agents (GCAs). A modified fluorescein flowmetry technique and 24 h necropsy were used in mice (conventional and germ free), rats, and guinea pigs after GCA administration. Different diets and oral nonabsorbable antibiotics were used. Nonfluorescence, edema, congestion, hemorrhage, and mucosal erosion in cecum and colon and nonfluorescent areas in the liver were observed from 16 min after GCA administration in conventional mice on standard diet. Numerous gas bubbles (>50 microm) were observed in the vasculature around the nonfluorescent areas of cecum and colon and in mesenteric vessels draining to the portal vein. Acute inflammation, edema, hemorrhage, and ulceration of the cecum and colon and liver necrosis were seen 24 h after GCA administration in conventional mice on standard diet. When mice were maintained on either a diet with glucose as the only carbohydrate source or on a standard diet supplemented with antibiotics, uniform fluorescence and no organ lesions were observed after GCA administration. Uniform fluorescence and no organ lesions were observed in germ-free mice, rats, and guinea pigs dosed with GCAs and in control animals (mice, rats, and guinea pigs) dosed with sucrose. The results indicate that intravascular growth of GCA microbubbles occurs in the cecal and colonic wall of mice, leading to occlusive ischemia and necrosis in these intestinal segments and secondary gas embolisation in the liver. Transmural gas supersaturation in the cecal wall may explain the intravascular bubble growth in mice.
Rasmussen
H
H
Research and Development, Amersham Health AS, N-0401, Oslo, Norway. henrik.rasmussen@amersham.com
Dirven
H A A M
HA
Grant
D
D
Johnsen
H
H
Midtvedt
T
T
D000418:Albumins / Q000493:pharmacokinetics / Q000633:toxicity; D000821:Animal Feed; D000818:Animals; D002429:Cecal Diseases / Q000139:chemically induced* / Q000473:pathology; D002432:Cecum / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury; D003287:Contrast Media / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005290:Ferric Compounds / Q000493:pharmacokinetics / Q000633:toxicity; D005466:Fluorocarbons / Q000493:pharmacokinetics / Q000633:toxicity; D005740:Gases / Q000633:toxicity*; D006168:Guinea Pigs; D007275:Injections, Intravenous; D007501:Iron / Q000493:pharmacokinetics / Q000633:toxicity; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D010087:Oxides / Q000493:pharmacokinetics / Q000633:toxicity; D011134:Polysaccharides / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms; D014018:Tissue Distribution; D014463:Ultrasonography / Q000009:adverse effects*
D000418:Albumins; D003287:Contrast Media; C099458:FS 069; D005290:Ferric Compounds; D005466:Fluorocarbons; D005740:Gases; D010087:Oxides; D011134:Polysaccharides; C069727:Sonazoid; C059891:SHU 508; D007501:Iron