Effect of hypothermia on the in vitro potencies of neuromuscular blocking agents and on their antagonism by neostigmine.
The effect of temperature on the potencies of neuromuscular blocking agents remains unclear. This study was undertaken to examine the effects of different neuromuscular blocking agents at 37 and 27 degrees C at a constant carbon dioxide content (alpha stat principle). The effect of neostigmine 1 mumol litre-1 induced antagonism of these agents was also investigated. Phrenic nerve-hemidiaphragm preparations of rats were mounted in modified Krebs solution, maintained at 37 degrees C and aerated with a 5% carbon dioxide-95% oxygen gas mixture, and at 27 degrees C with 4% carbon dioxide to maintain the carbon dioxide content of the solution constant. Phrenic nerves were stimulated with 0.1-Hz supra-maximal impulses of 0.2-ms duration and the elicited tension of the diaphragm recorded. The potencies of the steroidal neuromuscular blocking agents (rocuronium, vecuronium, pancuronium and pipecuronium) increased significantly at 27 degrees C (P < 0.05), while the potencies of the benzylisoquinolinium agents (tubocurarine and dimethyltubocurarine) did not change. Neostigmine-induced antagonism of the steroidal agents did not differ significantly between each other but differed significantly from the benzylisoquinolinium agents (P < 0.05) at both temperatures. The ratios of IC50 (inhibitory concentration, 50%) with and without neostigmine at hypothermia were slightly higher for the steroidal agents, indicating slight enhancement of antagonism by neostigmine at 27 degrees C. In contrast, the ratios were significantly greater at 27 degrees C (P < 0.05) for isoquinolinium agents, implying significant enhancement of antagonism. Our results indicate that at 27 degrees C the potency of all steroidal agents increased and neostigmine-induced antagonism was slightly enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
Aziz
L
L
Department of Anaesthesiology and Resuscitology, Okayama University Medical School, Japan.
Ono
K
K
Ohta
Y
Y
Morita
K
K
Hirakawa
M
M
D000818:Animals; D001831:Body Temperature; D002245:Carbon Dioxide; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009388:Neostigmine / Q000494:pharmacology*; D009466:Neuromuscular Blocking Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects; D010791:Phrenic Nerve / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D009466:Neuromuscular Blocking Agents; D002245:Carbon Dioxide; D009388:Neostigmine