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Cholinergic stimulation with pyridostigmine protects against exercise induced myocardial ischaemia
  1. R R T Castro1,*,
  2. G Porphirio2,,
  3. S M Serra2,,
  4. A C L Nóbrega1,*
  1. 1Department of Physiology and Pharmacology, Universidade Federal Fluminense, Niterói, Brazil
  2. 2Post-Graduate Program in Cardiology, Universidade Federal Fluminense, Niterói, Brazil
  1. Correspondence to:
    Dr A C L Nóbrega
    Rua Cinco de Julho, 318/1001, Niterói, RJ 24220-111, Brazil; anobregaurbi.com.br

Abstract

Objective: To determine the acute effects of pyridostigmine bromide, a reversible cholinesterase inhibitor, during exercise in patients with coronary artery disease.

Design: Double blind, randomised, placebo controlled, crossover study.

Setting: Outpatients evaluated in an exercise test laboratory.

Patients: 15 patients with exercise induced myocardial ischaemia.

Interventions: Maximal cardiopulmonary exercise test on a treadmill according to an individualised ramp protocol on three days. The first day was used for adaptation to the equipment and to determine exercise tolerance and the presence of exercise induced ischaemia. On the other two days, the cardiopulmonary exercise test was performed two hours after oral administration of pyridostigmine (45 mg) or placebo. All patients were taking their usual medication during the experiments.

Main outcome measures: Rate–pressure product and oxygen uptake during exercise.

Results: Pyridostigmine inhibited the submaximum chronotropic response (p  =  0.001), delaying the onset of myocardial ischaemia, which occurred at a similar rate–pressure product (mean (SE) placebo 20.55 (1.08) mm Hg × beats/min 103; pyridostigmine 19.75 (1.28) mm Hg × beats/min 103; p  =  0.27) but at a higher exercise intensity (oxygen consumption: placebo 18.6 (1.7) ml/kg/min; pyridostigmine 19.6 (1.8) ml/kg/min; p  =  0.03). Also, pyridostigmine increased peak oxygen consumption (placebo 23.6 (2) ml/kg/min; pyridostigmine 24.8 (2) ml/kg/min; p  =  0.01) and peak oxygen pulse (placebo 12.9 (1) ml/beat; pyridostigmine 13.6 (1) ml/beat; p  =  0.02).

Conclusions: Pyridostigmine improved peak exercise tolerance and inhibited the chronotropic response to submaximum exercise, increasing the intensity at which myocardial ischaemia occurred. These results suggest that pyridostigmine can protect against exercise induced myocardial ischaemia.

  • co2, carbon dioxide production
  • e, minute ventilation
  • o2, oxygen consumption
  • pyridostigmine
  • autonomic nervous system
  • stable angina
  • exercise test
  • maximum oxygen consumption

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Footnotes

  • * Also Post-Graduate Program in Cardiology, Universidade Federal Fluminense, Brazil

  • Also Aloysio de Castro State Institute of Cardiology, Rio de Janeiro, Brazil