Cholinergic stimulation with pyridostigmine protects against exercise induced myocardial ischaemia.
OBJECTIVE
To determine the acute effects of pyridostigmine bromide, a reversible cholinesterase inhibitor, during exercise in patients with coronary artery disease.


METHODS
Double blind, randomised, placebo controlled, crossover study.


METHODS
Outpatients evaluated in an exercise test laboratory.


METHODS
15 patients with exercise induced myocardial ischaemia.


METHODS
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.


METHODS
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 x beats/min 10(3); pyridostigmine 19.75 (1.28) mm Hg x beats/min 10(3); 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.
Castro
R R T
RR
Department of Physiology and Pharmacology, Universidade Federal Fluminense, Niterói, Brazil.
Porphirio
G
G
Serra
S M
SM
Nóbrega
A C L
AC
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise; D017079:Exercise Tolerance; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000209:etiology / Q000517:prevention & control*; D010101:Oxygen Consumption; D011729:Pyridostigmine Bromide / Q000627:therapeutic use*
D002800:Cholinesterase Inhibitors; D011729:Pyridostigmine Bromide