British journal of anaesthesia
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We have examined the in vitro sensitivities of A, B and C fibres in rabbit vagus nerves to local anaesthetic block with a range of local anaesthetic drugs. The nerves were maintained at 37 degrees C and pH 7.4 using an electrolyte solution equilibrated with 5% carbon dioxide. A fibres were the most, and C fibres the least, sensitive to block at low frequency stimulation (0.0167 Hz). ⋯ With stimulation at high frequencies (20 and 40 Hz), C fibres were more sensitive to use-dependent block than A fibres; this effect was more marked with drugs containing an amide than an ester linkage. Molecular size and lipid solubility may inter-react to govern the ability to produce use dependent block. Agents which contain an amide linking group, have a high pKa and are of low lipid solubility, may be used to produce differential C fibre block.
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To quantify the neuromuscular blocking effect of vecuronium on the diaphragm and the adductor pollicis, single twitch stimuli were applied to the phrenic nerves at the neck and the ulnar nerve at the wrist in anaesthetized patients. The evoked responses were measured simultaneously by recording the transdiaphragmatic pressure with a differential pressure transducer and the adductor pollicis strength with a force displacement transducer. ⋯ The mean (SD) doses required to depress adductor pollicis and diaphragm responses to 50% (ED50) were 30 (9) micrograms kg-1 and 37 (12) micrograms kg-1, respectively. Corresponding values for 95% depression of the twitch response (ED95) were 48 (13) micrograms kg-1 and 67 (23) micrograms kg-1 (P less than 0.02), indicating that the diaphragm required approximately 40% more vecuronium for subtotal abolition of the single twitch response.
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The effects of Org 9426 (the 2-morpholino, 3-hydroxy, 16N-allyl pyrrolidino analogue of vecuronium) were studied in anaesthetized cats and pigs and in isolated nerve--muscle preparations using tension and intracellular recording techniques. In isolated preparations, the effects of Org 9426 were antagonized by neostigmine. No contracture of the chick muscle preparation occurred. ⋯ Ganglion block was seen only at doses several times those producing vagal block. In general the effects of Org 9426 on the cardiovascular system were slight, a small depressor effect occurring at high doses in the cat. The 17-hydroxy analogue, the potential metabolite of Org 9426, was approximately 20 times less potent than Org 9426 and is thus unlikely to contribute to the neuromuscular block produced by the parent compound.