Effects of neuromuscular-blocking drugs in rats in vivo: direct measurements in the diaphragm and tibialis anterior muscle.
BACKGROUND
Effects of neuromuscular-blocking drugs are often investigated in rodents using both the diaphragm in vitro and the tibialis anterior muscle in vivo. Differences in the properties of these muscles cannot be neglected. We evaluated the neuromuscular effects of drugs on the rat diaphragm in vivo in comparison with the tibialis anterior muscle, directly measuring twitch tension with a force transducer.


METHODS
Respectively using sternotomy and an approach via the gluteal space, transducers were attached to the diaphragm and the tibialis anterior muscle. Phrenic and sciatic nerves were stimulated supramaximally by single square pulses to record isometric contraction of muscles. Pancuronium, vecuronium, or rocuronium was infused continuously at a rate adjusted repeatedly until stable tension was obtained. Effective doses for 50% (ED 50) and 90% (ED 90) depression of tension were calculated, using a cumulative infusion dosing method.


RESULTS
Isometric contraction of the diaphragm could be recorded despite movements of the heart and lungs. For all three drugs, both mean ED 50 and ED 90 were more than twice as large for the diaphragm as for the tibialis anterior (P<0.05). In addition, slopes of dose-response curves for the diaphragm were significantly less steep than those of the tibialis anterior for the three drugs.


CONCLUSIONS
Neuromuscular-blocking effects on the diaphragm can be recorded in vivo. According to direct contractile force measurement, the diaphragm is more resistant to non-depolarizing neuromuscular-blocking drugs than the tibialis anterior muscle.
Itoh
H
H
Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. hironori@med.kanazawa-u.ac.jp
Shibata
K
K
Matsumoto
T
T
Nitta
S
S
Nishi
M
M
Kobayashi
T
T
Yamamoto
K
K
D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009466:Neuromuscular Blocking Agents