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 a gents remains unclear. This study was undertaken to examine the effect s 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 mu mol litre(-1) induced antagonism of these agents w as also investigated. Phrenic nerve-hemidiaphragm preparations of rats were mounted in modified Krebs solution, maintained at 37 degrees C a nd aerated with a 5% carbon dioxide-95% oxygen gas mixture, and at 27 degrees C with 4% carbon dioxide to maintain the carbon dioxide conten t of the solution constant. Phrenic nerves were stimulated with 0.1-Hz supramaximal impulses of 0.2-ms duration and the elicited tension of the diaphragm recorded. The potencies of the steroidal neuromuscular b locking agents (rocuronium, vecuronium, pancuronium and pipecuronium) increased significantly at 27 degrees C (P < 0.05), while the potencie s of the benzylisoquinolinium agents (tubocurarine and dimethyltubocur arine) did not change. Neostigmine-induced antagonism of the steroidal agents did not differ significantly between each other but differed s ignificantly from the benzylisoquinolinium agents (P < 0.05) at both t emperatures. The ratios of IC50 (inhibitory concentration, 50%) with a nd without neostigmine at hypothermia were slightly higher for the ste roidal agents, indicating slight enhancement of antagonism by neostigm ine at 27 degrees C. In contrast, the ratios were significantly greate r at 27 degrees C (P < 0.05) for isoquinolinium agents, implying signi ficant enhancement of antagonism. Our results indicate that at 27 degr ees C the potency of all steroidal agents increased and neostigmine-in duced antagonism was slightly enhanced. With the isoquinolinium agents , hypothermia caused no change in potency although neostigmine-induced antagonism was enhanced significantly. These findings suggest that th e relative effects of steroidal and isoquinolinium agents on the neuro muscular junction are different or that they have a different mechanis m of action on the neuromuscular junction.