Studies of the toxicity of I-653, halothane, and isoflurane in enzyme-induced, hypoxic rats.
The physical stability and low blood solubility of the new inhaled anesthetic, I-653, imply that this agent produces limited or no toxic effects. To test this possibility, its effects were compared with those of other volatile agents on hepatic, renal, and pulmonary specimens taken from enzyme-induced, hypoxic rats. Male Sprague-Dawley rats were pretreated with phenobarbital and exposed for 1 hr to 12% O2 and no anesthesia (control) or to 1.2 MAC of one of three anesthetics: I-653, isoflurane, or halothane. Liver, kidney, and lung specimens were taken 24 hr after exposure concluded. The livers of all rats given halothane (n = 6) had swelling (20.5 +/- 5.7% of a lobule [mean +/- SD]) and centrilobular necrosis (6.7 +/- 2.1% of a lobule). Isoflurane produced only slight injury (6.7 +/- 3.5% swelling and 1.0 +/- 0.0% necrosis in 3 of 15 rats). No hepatic injury occurred in control rats (n = 20) or in those given I-653 (n = 16). Pulmonary and renal injury were not evident with any agent. Results suggest that I-653 has equivalent or less effect on hepatic, renal, and pulmonary integrity than currently available inhaled anesthetics.
Eger
E I
EI
Department of Anesthesia, University of California, San Francisco 94143-0542.
Johnson
B H
BH
Strum
D P
DP
Ferrell
L D
LD
D000777:Anesthetics / Q000633:toxicity; D000818:Animals; D000077335:Desflurane; D004790:Enzyme Induction / Q000187:drug effects; D006221:Halothane / Q000633:toxicity*; D000860:Hypoxia / Q000503:physiopathology; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats
D000777:Anesthetics; D000077335:Desflurane; D007530:Isoflurane; D006221:Halothane; D010634:Phenobarbital