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J M K H Wierda

Publications and source records attributed to J M K H Wierda.

3 recordsLinked to original sources
PubMed2005

Decreased number of acetylcholine receptors is the mechanism that alters the time course of muscle relaxants in myasthenia gravis: a study in a rat model.

BACKGROUND: In myasthenic patients, the time course of action of non-depolarizing neuromuscular blocking agents is prolonged and the sensitivity is increased. We used our antegrade perfused rat peroneal nerve anterior tibialis muscle model to investigate if this altered time course of effect and sensitivity can be explained by the decreased acetylcholine receptor concentration that is caused by the disease. METHODS: Functional acetylcholine receptors were reduced by administration of alpha-bungarotoxin or by injecting monoclonal antibodies against rat acetylcholine receptors (experimental autoimmune myasthenia gravis). After induction of anaesthesia, the model was set up and perfusion of the tibialis anterior muscle with blood was started. After stabilization of the twitch, rocuronium or pancuronium were infused until 90% block was obtained. Twitch data and infusion data were recorded and used to calculate the time course of effect and potency. RESULTS: The potency of neuromuscular blocking agents was increased and the offset of the neuromuscular block was prolonged in both the alpha-bungarotoxin groups and the experimental autoimmune myasthenia gravis groups compared to controls. CONCLUSION: This study shows that the increased sensitivity to neuromuscular-blocking agents in myasthenia gravis can be accounted for by a decreased number of acetylcholine receptors. It also shows that the antegrade perfused rat peroneal nerve anterior tibialis muscle model is a suitable model to study the effects of myasthenia gravis on the time course of effect of neuromuscular blocking agents.

Androstanols↗
PubMed2004

Model to describe the degree of twitch potentiation during neuromuscular monitoring.

BACKGROUND: Neuromuscular block is estimated by comparing the evoked peak twitch with a control value measured in the absence of neuromuscular block. In practice, this control value is often difficult to determine because repeated motor nerve stimulation enhances the evoked mechanical response of the corresponding muscle, resulting in an increased twitch response. This is known as twitch potentiation or the staircase phenomenon. It is probably the result of myosin light chain phosphorylation creating an increased twitch force for a given amount of Ca(2+) released at each action potential. Modelling of potentiation may improve studies of neuromuscular blocking agents using mechanomyography or accelerometry. METHODS: We used one- and two-exponential models to describe the degree of myosin light chain phosphorylation and associated twitch potentiation. These models were fitted to accelerographic twitch force measurements for various stimulation patterns and frequencies used in neuromuscular monitoring. RESULTS: Fitting a two-exponential model to twitch data for various stimulation rates and patterns provides better prediction than a one-exponential model. A one-exponential model performs poorly when the stimulation rate varies during measurement. CONCLUSIONS: We conclude that a two-exponential model can predict the degree of twitch potentiation for the stimulation patterns and frequencies tested more accurately than a one-exponential model. However, if only one stimulation frequency is used, a one-exponential model can provide good accuracy. We illustrate that such a potentiation model can improve the ability of pharmacodynamic-pharmacokinetic neuromuscular block models to predict twitch response in the presence of a neuromuscular blocking agent.

Electric Stimulation↗