Hepatotoxicity and metabolism of isoflurane in rats with cirrhosis.
A rat model was used to determine whether isoflurane exacerbates liver dysfunction and whether its metabolism is changed in the presence of cirrhosis. Male Wistar rats were gavaged weekly with carbon tetrachloride until cirrhosis was well advanced. They and control rats without pretreatment with carbon tetrachloride and without cirrhosis were then exposed to 1.45% (1 MAC) isoflurane for 3 hours. Blood and urine samples were taken before, immediately, as well as 4, 24, 48, and 72 hours after anesthesia to measure liver function and isoflurane defluorination. After the last samples had been obtained, the rats were sacrificed and the liver removed for histologic examination and in vitro metabolic studies. Serum levels of SGOT and SGPT and inorganic fluoride production in rats with cirrhosis were similar to those in control rats without cirrhosis. Concentrations of cytochromes b5 and p-450 and specific activities of microsomal defluorinase and several cytosolic enzymes were significantly lower in cirrhotic than in noncirrhotic liver, but their total amounts in whole liver were the same. The results imply that cirrhosis does not increase the risk of acute hepatotoxicity of isoflurane. They also demonstrate that metabolism of isoflurane and perhaps other volatile anesthetics may be unaffected in rats with cirrhosis, even though liver architecture is severely disrupted.
Baden
J M
JM
Department of Anesthesia, Stanford University School of Medicine, California.
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005459:Fluorides / Q000378:metabolism; D007530:Isoflurane / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D007530:Isoflurane; D005459:Fluorides