Use of a head dome system to compare i.v. methacholine-induced bronchoconstriction in conscious vs anesthetized rhesus monkeys.
The use of a newly developed head dome system has allowed measurement of pulmonary function in conscious monkeys. Such information is often desired, so that pharmacological or toxicological effects of administered compounds can be measured in the absence of effects from anesthetic agents. The current study was conducted to gain experience with this method and to allow the determination of the effects of sodium pentobarbital anesthesia (30 mg kg-1 i.v.) on the bronchoconstriction seen during i.v. infusion of methacholine in rhesus monkeys. Bronchoconstriction was measured as changes in respiratory resistance using a Buxco LS20 pulmonary mechanics computer. Four male rhesus monkeys (4.2-5.1 kg) were used. For the anesthetized exposures, the animals were intubated with a 4.0-mm cuffed endotracheal tube attached to a size 'O' Fleisch pneumotachograph. For the conscious exposures, the animals sat in restraining chairs with a custom-built head dome attached to the same pneumotachograph. In both cases, transthoracic pressure was monitored with an intrapleural catheter. Each monkey was infused with methacholine in stepwise doses, while anesthetized and conscious, until a 75% increase in respiratory resistance was seen. The ED50 values of 0.134 and 0.180 mg ml-1 methacholine were not significantly different in anesthetized vs conscious monkeys, respectively.
Allen
D L
DL
Toxicology Research Laboratory, Lilly Research Laboratories, Division of Eli Lilly and Company, Greenfield, IN 46140, USA.
Pollard
K R
KR
Hughes
B L
BL
Dorato
M A
MA
Wolff
R K
RK
D000403:Airway Resistance / Q000187:drug effects*; D000758:Anesthesia; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007262:Infusions, Intravenous; D008253:Macaca mulatta; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000633:toxicity*; D010424:Pentobarbital; D012129:Respiratory Function Tests; D012984:Software
D016210:Methacholine Chloride; D010424:Pentobarbital