Cholinergic Stimulation Improves Autonomic and Hemodynamic Profile During Dynamic Exercise in Patients With Heart Failure

• Published in: Journal of cardiac failure 2009-03, Vol.15 (2), p.124-129
• Main Authors: Serra, Salvador Manoel, MD, ScD, Costa, Ricardo Vivacqua, MD, ScD, Teixeira De Castro, Renata Rodrigues, MD, MSc, Xavier, Sergio Salles, MD, ScD, Lucas Da Nóbrega, Antonio Claudio, MD, ScD
• Format: Article
• Language: English
• Subjects: acetylcholinesterase; Acetylcholinesterase - drug effects; Adaptation, Physiological; Analysis of Variance; Autonomic nervous system; Autonomic Nervous System - physiopathology; Cardiovascular; Cholinesterase Inhibitors - therapeutic use; Cross-Over Studies; Double-Blind Method; Exercise Test; Female; Heart Failure - drug therapy; Heart Failure - metabolism; Heart Failure - physiopathology; Heart Failure - rehabilitation; Hemodynamics; Humans; Male; Middle Aged; oxygen pulse; Pyridostigmine Bromide - therapeutic use; Receptors, Cholinergic - metabolism; Risk Factors; Stroke Volume; vagal
• ISSN: 1071-9164; 1532-8414
• DOI: 10.1016/j.cardfail.2008.10.018

Abstract Background Parasympathetic dysfunction is an independent risk factor for mortality in heart failure for which there is no specific pharmacologic treatment. This article aims to determine the effect of pyridostigmine, an anticholinesterase agent, on the integrated physiologic responses to dynamic exercise in heart failure. Methods and Results Patients with chronic heart failure (n = 23; 9 female; age = 48 ± 12 years) were submitted to 3 maximal cardiopulmonary exercise tests on treadmill in different days. The first test was used for adaptation and to determine exercise tolerance. The other tests were performed after oral administration of pyridostigmine (45 mg, 3 times/day, for 24 hours) or placebo, in random order. All patients were taking their usual medication. Pyridostigmine reduced cholinesterase activity by 30%, inhibited the chronotropic response throughout exercise, up to 60% of maximal effort (pyridostigmine = 108 ± 3 beats/min vs. placebo = 113 ± 3 beats/min; P = .040), and improved heart rate reserve (pyridostigmine = 73 ± 5 beats/min vs. placebo = 69 ± 5 beats/min; P = 0.035) and heart rate recovery in the first minute after exercise (pyridostigmine = 25 ± 2 beats/min vs. placebo = 22 ± 2 beats/min; P = .005), whereas peak heart rate was similar to placebo. Oxygen pulse, an indirect indicator of stroke volume, was higher under pyridostigmine during submaximal exercise. Conclusions Pyridostigmine was well tolerated by heart failure patients, leading to improved hemodynamic profile during dynamic exercise.