An isolated, antegrade, perfused, peroneal nerve anterior tibialis muscle model in the rat: a novel model developed to study the factors governing the time course of action of neuromuscular blocking agents.
BACKGROUND
A model of an antegrade, perfused, isolated rat peroneal nerve anterior tibial muscle was developed to study potentially important factors governing the time course of action of (nondepolarizing) neuromuscular blocking agents such as concentration, blood flow, and temperature. The model allows observation of the effects of selective changes in these factors.


METHODS
The authors isolated the anterior tibial muscle and cannulated the anterior tibial artery and vein, providing a way for single-pass perfusion with blood from a donor rat. A force transducer was connected to the tibialis anterior muscle and a stimulator was connected to the tibial nerve. The influence of intrinsic potency (EC90) and muscle blood flow rate on the time course of pancuronium and rocuronium was investigated.


RESULTS
The model remained stable for at least 4 h with respect to twitch height, muscle structure and function, and blood chemistry. Doubling the muscle-blood flow resulted in a significantly faster onset and offset for both pancuronium and rocuronium. Trebling the intrinsic potency (EC90) was not associated with significant changes in the time course of action of the relaxants.


CONCLUSIONS
The authors developed and validated a model that allows us to study biophase kinetics of neuromuscular blocking agents in the anterior tibial muscle of the rat. In this model, muscle-blood flow rather than EC90 appears to predominantly determine the onset and offset time of nondepolarizing muscle relaxants.
De Haes
Ann
A
Research Group for Experimental Anesthesiology and Clinical Pharmacology, University of Groningen, Groningen, The Netherlands.
Houwertjes
Martin C
MC
Proost
Johannes H
JH
Wierda
J Mark K H
JM
D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D010197:Pancuronium / Q000494:pharmacology; D010477:Perfusion; D010543:Peroneal Nerve / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D000077123:Rocuronium; D013977:Tibia
D000732:Androstanols; D009466:Neuromuscular Blocking Agents; D010197:Pancuronium; D000077123:Rocuronium