Abstract
Purpose
The bradycardia produced by pyridostigmine and physostigmine in an animal model of acute cardiac denervation was examined according to its relation to cholinesterase inhibition and sensitivity to block by cholinergic receptor antagonists.
Methods
Cats were anaesthetised, vagotomised and propranolol-treated. Heart rate was continuously recorded. Erythrocyte cholinesterase activity of arterial blood was measured using a radiometric technique. Nicotinic and muscarinic M1 receptors were blocked with hexamethonium and pirenzepine, respectively. M2 receptors were blocked with gallamine, pancuronium and AFDX-116.
Results
With pyridostigmine and physostigmine, the dose-response relationship for the decrease in heart rate (ED50 1.05 ± 0.25 and 0.198 ± 0.03 mg·kg−1, respectively) was shifted to the right of that for the inhibition of cholinesterase activity (ED50 0.094 ± 0.03 and 0.032 ± 0.01 mg·kg−1, respectively). The decrease in cholinesterase activity reached a plateau at a cumulative dose of 0.56 ± 0.08 and 0.32 ± 0.08 mg·kg−1, respectively. In contrast, there did not appear to be a plateau in the bradycardic effect. The bradycardia produced by pyndostigmine and physostigmine was blocked by hexamethonium (ED50 10 ± 1.3 and 15.3 ± 2.4 mg·kg−1, respectively), pirenzepine (ED50 68 ± 16 and 138 ± 32 μg·kg−1. respectively), gallamine (56 ± 11 and 67 ± 17 μg·kg−1, respectively ), pancuronium (32 ± 10 and 30 ± 4 μg·kg−1, respectively), and AFDX-116 (31 ± 4 and 28 ± 4 μg·kg−1, respectively).
Conclusion
The bradycardia produced by reversible anticholinesterase drugs containing a carbamyl group is not dearly related to the degree of cholinesterase activity, and has a low sensitivity to nicotinic and muscannic M1 and a high sensitivity to muscarinic M2 receptor antagonists.
Résumé
Objectif
Examiner si la bradycardie provoquée par la physostigmine et la pyndostigmine sur un modèle de dénervation cardiaque animal est en rapport avec l’inhibition de la cholinestérase et la sensibilité au bloc du récepteur cholinergique par ses antagonistes.
Méthodes
Des chats ont été anesthésiés, vagotomisés et traités au propanolol. Leur fréquence cardiaque a été enregistrée continuellement. Une technique radiométnque a permis de mesurer dans le sang artériel l’activité de la cholinestérase érythrocytaire. On a bloqué les récepteurs nicotiniques avec de l’hexaméthonium et les récepteurs muscariniques M1 avec de la pirenzépine. Les récepteurs M2 étaient bloqués avec de la gallamine, du pancuronium et de l’AFDX-116.
Résultats
Avec la pyridostigmine et la physostigmine, la relation dose-effet en rapport avec la baisse de la fréquence cardiaque (ED50 respective de 1,05 ± 0,25 et de 0,198 ± 0,03 mg·kg−1) a dévié vers la droite de celle de l’inhibition de l’activité cholinestérasique (ED50 respective de 0,094 ± 0,03 et 0,032 ± 0.01 mg·kg−1). La baisse de l’activité cholinestérasique a atteint un plateau à la dose cumulative respective de 0,56 ± 0,08 et 0,32 ± 0,08 mg·kg−1. Par contre, il ne semblait pas y avoir de plateau en ce qui concerne l’effet bradycardisant. La bradycardie provoquée par la pyridostigmine et la physostigmine était bloquée par l’héxaméthonium (ED50 respective de 10 ± 1,3 et de 15,3 ± 2,4 mg·kg−1), la pérenzépine (ED50 respective de 68 ± 16 et de 138 ± 32 μg·kg−1), la gallamine (respectivement 56 ± 11 et 67 ± 17 μg·kg−1), le pancuronium (respectivement 32 ± 10 et 30 ± 4 μg·kg−1) et l’AFDX-116 (respectivement 31 ± 4 et 28 ± 4 μg·kg−1).
Conclusion
La bradycardie provoquée par les anticholinestérases réversibles porteuses d’un groupe carbamyl n’a pas de relation certaine avec le degré d’activité cholinestérasique et est faiblement sensible aux antagonistes du récepteur nicotinique et muscarinique M1, et fortement sensible aux antagonistes du récepteur muscarinique M2.
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This work was supported by grants from the Canadian Anaesthetists’ Society and the Royal Victoria Hospital Research Institute to SBB and from the Medical Research Council to BC. Preliminary results presented in part at the CAS 1994 Annual Meeting in Edmonton, Alberta).
An erratum to this article is available at http://dx.doi.org/10.1007/BF03012039.
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Stein, R.D., Backman, S.B., Collier, B. et al. Bradycardia produced by pyridostigmine and physostigmine. Can J Anaesth 44, 1286–1292 (1997). https://doi.org/10.1007/BF03012778
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DOI: https://doi.org/10.1007/BF03012778