Hyperammonemic coma after hepatectomy in germ-free rats.
Current theories on the pathogenesis of hepatic coma indicate that intestinal bacteria produce cerebral toxins, such as ammonia, mercaptans, and short-chain fatty acids. To test the hypothesis that elimination of anaerobic and aerobic intestinal bacteria retards the onset and alters the biochemical profile of acute hepatic coma, we determined the onset of coma and the ammonia concentration in blood and cecal contents in 7 germ-free and 10 normal dehepatized rats. Ammonia levels were also determined in a further group of 7 germ-free and 12 normal rats 24 hr after hepatic vascular exclusion was accomplished. Onset of coma for germ-free rats (x: 34 hr) was identical to that of normal rats (x: 36 hr). Arterial ammonia was equally elevated in germ-free rats (x: 834 mumol/liter) and in normal rats (x: 854 mumol/liter), although the ammonia concentration in the cecal contents was significantly lower in germ-free rats (x: 1762 mumol/liter) than in normal rats (x: 5572 mumol/liter). In germ-free animals, portal venous blood contained more ammonia than arterial blood (x A-V difference: -87 mumol/liter), indicating nonbacterial intestinal ammonia release. We conclude that intestinal bacteria toxins are of minor importance in the mechanism of acute hepatic coma of the liverless rat and that presumably bacterial toxins, such as ammonia, can be products of nonbacterial metabolism. Since hyperammonemia could be considered an important determinant of coma in our model, prevention of hyperammonemia in functionally anhepatic animals should be the next objective in unraveling the pathogenesis of acute hepatic coma.
D000641:Ammonia / Q000097:blood* / Q000378:metabolism; D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D001427:Bacterial Toxins / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005856:Germ-Free Life; D006498:Hepatectomy; D006501:Hepatic Encephalopathy / Q000209:etiology* / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D008297:Male; D011169:Portal Vein; D051381:Rats
D001427:Bacterial Toxins; D000641:Ammonia