Some effects of d-tubocurarine alone and combined with halothane or isoflurane on neuromuscular transmission.
The mechanisms contributing to the neuromuscular block produced by nondepolarizing muscle relaxants and inhaled anesthetics include: 1) receptor blockade, 2) open or closed ion channel block, 3) decreased transmitter release, and 4) receptor desensitization. In this study we investigated the contributions of receptor and ion channel block. We used the two microelectrode voltage clamp to evaluate miniature end-plate currents (MEPCs) for amplitude and time constant of decay (tau) before and after the application of 1) d-Tubocurarine (DTC) (10(-7)-10(-6) M) alone, and then 2) the same concentration of DTC plus 0.5% or 1.0% halothane or isoflurane delivered by passing compressed air through a flow and temperature compensated vaporizer. The electrodes were maintained in the same cell for the entire experiment. DTC alone decreased MEPC amplitude to 91.3% +/- 4.5% and 65.1% +/- 5.6% of control at 10(-7) and 10(-6) M, respectively. MEPC amplitude with 10(-6) M DTC decreased further to 52.4% +/- 7.6% and 37.4% +/- 7.0% of control after the addition of 0.5% and 1.0% halothane, respectively. After the application of DTC 10(-7) M tau was 94.7% +/- 3.1% of control and decreased to 73.7% +/- 7.1% of control with 10(-6) M DTC. After the application of DTC 10(-6) M the addition of 0.5% and 1% halothane decreased tau to 52.4% +/- 7.6% and 30.0% +/- 5.9% of control. Isoflurane produced similar changes. This study provides evidence that at least some of the augmentation of nondepolarizing relaxants by inhaled anesthetics can be explained by the additive effect of nondepolarizing muscle relaxants and inhaled anesthetics on MEPC amplitude and tau.
Sokoll
M D
MD
Department of Anesthesia Laboratories, University of Iowa College of Medicine, Iowa City, USA.
Bhattacharyya
B J
BJ
Davies
L R
LR
Zwagerman
D Q
DQ
D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018680:Cholinergic Antagonists; D006221:Halothane / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011898:Ranidae; D009435:Synaptic Transmission / Q000187:drug effects*; D014403:Tubocurarine / Q000008:administration & dosage / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D018680:Cholinergic Antagonists; D003473:Neuromuscular Nondepolarizing Agents; D007530:Isoflurane; D006221:Halothane; D014403:Tubocurarine