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Biomedical subjects

A J de Silva

Publications and source records attributed to A J de Silva.

6 recordsLinked to original sources

Interaction of neuromuscular blocking effects of neomycin and polymyxin B.

Neomycin and polymyxin B produce neuromuscular blocks with distinct features by different mechanisms of action. In eight anesthetized cats the authors studied their interaction by examining the neuromuscular block produced by an equipotent mixture. Values of onset, potency, dose-response relations, duration and reversibility of block, the train-of-four and tetanic responses during block, the frequency-block relationships, and the posttetanic twitch behavior were well approximated by averaging the corresponding values previously reported for each antibiotic. Edrophonium, 0.2 mg/kg, reversed the block by 8 to 35 per cent. 4-Aminopyridine, 0.6 mg/kg, completely reversed the block and caused a long-lasting overshoot of the twitch response. The authors conclude that neomycin and polymyxin B are additive in neuromuscular effects, not only in terms of potency and duration, but also in terms of the characteristics of the blocks produced.

Aminopyridines

Neuromuscular and cardiovascular depression produced by prolonged exposure to Polymyxin B.

It has been reported previously that in cats pre-treatment for 24 to 48 hours with neomycin sulphate resulted in a change in the pattern of neuromuscular block subsequently produced with this antibiotic. The unique characteristics of neomycin-induced neuromuscular block observed during acute exposure gave way to a pattern of block usually observed with tubocurarine. In a similar experiment on six cats we have demonstrated that with polymyxin B prolonged exposure did not result in a comparable time-dependent change in the nature of the neuromuscular block it produced, in terms of train-of-four, tetanic, and post-tetanic behaviour of the neurally-elicited muscle response. The differing characteristics of neuromuscular block seen with various antibiotics, e.g. the aminoglycoside neomycin as opposed to the polypeptide polymyxin B, during acute and sub-chronic exposure is stressed. Previously observed ability of 4 aminopyridine 0.6 mg/kg to reverse the neuromuscular and cardiovascular depression during acute exposure to polymyxin B persisted in prolonged exposure.

Animals

Neuromuscular refractoriness during blockage of transmission. A quantitative study.

The effects of suxamethonium and tubocurarine on the refractoriness of neuromuscular transmission were studied in 21 anaesthetized adult subjects under various levels of neuromuscular block. The ulnar nerve was stimulated every 12 s with twin supramaximal stimuli 4 ms apart. At any level of block, the refractory fraction (the fractional decrement of the compound electromyographic response of the adductor pollicis to the second twin stimulus, relative to the response to the first) was used to quantify neuromuscular refractoriness. The magnitude of block was determined by the response to the first stimulus. Correlation between refractoriness and the degree of block was sought. Without block, neuromuscular transmission averaged 23% (SEM 4) refractory with this twin interval. The refractory fraction was increased markedly by suxamethonium, reaching 0.69 (SEM 0.1) at 50% block. Complete refractoriness occurred during 25--75% block in eight of 11 instances. Tubocurarine did not significantly alter refractoriness, paired responses to the twin stimuli decreasing proportionately during block.

Adult

Multipeaking of the compound electromyographic response to single nerve stimulus: its occurrence and prevention in an experimental model.

The compound electromyographic response to a single nerve stimulus was examined in the cat tibialis anterior muscle preparation, to determine the cause of and to find a method of preventing multipeaking of the waveform. Bundles of the sciatic nerve were separated and stimulated while the response was detected by unipolar electrodes and analysed with an instrument specifically designed for this purpose. It was found that the most cephalad bundle of the sciatic nerve at the sciatic notch innervated the tibialis anterior muscle and that restriction of stimulation to this bundle most readily rendered the response single-peaked. It is concluded that nerve-branching is a common cause, and therefore a straightforward alternative to "repetitive response of the muscle" as the explanation, of multipeaking of the neurally-elicited compound electromyogram. A method of eliciting and recording the compound electromyogram in the cat tibialis anterior model is described.

Animals

Antagonism of polymyxin B-induced neuromuscular and cardiovascular depression by 4-aminopyridine in the anesthetized cat.

In an attempt to find a better antidote to polymyxin B-induced neuromuscular blockade, the authors tested 4-aminopyridine, 0.4--1 mg/kg, in ten anesthetized cats. The sciatic--tibialis anterior nerve--muscle preparation was used. The neuromuscular blockade was successfully reversed in all cats. Rapidity of reversal depended on the dose of 4-aminopyridine administered. At 0.6--1 mg/kg, reversal of the twitch response from 20 per cent of control to 80 per cent of control required 2.4 (SE, 0.5) min; to 100 per cent, 14.4 (SE, 3.7) min. An overshoot of the recovery of neuromuscular blockade of 6--10 hours' duration followed the reversal. The mechanical twitch response reached a peak of approximately 140 per cent of control at 2 hours. At a lower dosage, 0.4 mg/kg, two of three cats took more than an hour for complete recovery of the twitch response, and the overshoot was approximately 10 per cent of control. The hypotensive effect of polymyxin B was partially reversed, but the bradycardia was not. It is concluded that 4-aminopyridine is an effective antidote to polymyxin B-induced neuromuscular blockade in the cat.

Aminopyridines

Normocapnic ventilation using the circle system.

A formula is derived for maintaining normocapnia during controlled ventilation using a circle system without carbon dioxide absorption. In a series of 70 patients, unselected in terms of age, sex, obesity, ASA status, body position during operation, type of anaesthetic administered or type of circle system used, it was found that a total fresh gas flow of 50 ml/kg body weight/min and a minute ventilation of 120 to 150 ml/kg body weight at a rate of 10 to 12/min achieved normocapnia. For moderate hypocapnia a total fresh gas flow of 60 ml/kg body weight/min and a minute ventilation of 120 ml/kg at a rate of 10-12/min is suggested.

Adult