title: Pyridostigmine enhances atrial tachyarrhythmias in aging spontaneously hypertensive rats.
abstract: This study examined whether chronic administration of pyridostigmine, a reversible cholinesterase inhibitor, would exacerbate episodes of spontaneous atrial tachyarrhythmia (AT) in conscious, aging, spontaneously hypertensive rats (SHRs). Telemetric recordings of electrocardiogram (ECG, n = 5) and ECG/arterial pressure (n = 3) were performed in male 49-week old SHRs. After a 1-week period of continuous recording under baseline conditions, rats were implanted with osmotic minipumps that delivered pyridostigmine (15 mg/kg/day subcutaneously) for either 1 (n = 8) or 3 (n = 5) weeks. In the latter case, sympathovagal balance was assessed during the last infusion week by measuring heart rate (HR) changes in response to administration of cardiac autonomic blockers. An additional 1-week recording was performed after explantation of minipumps. Significant (P = 0.02) reductions in HR with no consistent changes in arterial pressure were observed. Frequency and duration of AT episodes were increased by pyridostigmine (0.01 ≤ P ≤ 0.07). This increase was sustained across the 3-week treatment period and reversible after cessation of treatment. Autonomic blockade revealed that intrinsic HR was above (P = 0.04) resting HR, pointing to a shift of sympathovagal balance towards vagal predominance. However, the respiratory-related component of HR variability (high-frequency power of RR interval) was lowered (P = 0.01) by pyridostigmine treatment, indicating reduced vagal modulation of HR. The results are consistent with a pathogenic role of the parasympathetic nervous system in the aging SHR model, and raise the possibility that sustained vagal activation may facilitate atrial arrhythmias.
authors.affiliation: Neurocardiology Unit, Medical School Lyon East, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Halil
authors.initials: H
authors.lastname: Sayin
authors.affiliation: Physiology Department, University of Medicine and Pharmacy of Tîrgu Mureș, Tîrgu Mureș, Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Scridon
authors.affiliation: Laboratory of Tissue Biology and Therapeutic Engineering, National Center for Scientific Research UMR 5305 and Technical Platform ANIPHY, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Oréa
authors.affiliation: Neurocardiology Unit, Medical School Lyon East, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Chapuis
authors.affiliation: Neurocardiology Unit, Medical School Lyon East, University Claude Bernard Lyon 1, Lyon, France.|Rhythmology Department, Louis Pradel Cardiology Hospital, Hospices Civils de Lyon, Bron, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chevalier
authors.affiliation: Neurocardiology Unit, Medical School Lyon East, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Barrès
authors.affiliation: Neurocardiology Unit, Medical School Lyon East, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Julien
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004562:Electrocardiography; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D013617:Tachycardia, Supraventricular / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D002800:Cholinesterase Inhibitors; D011729:Pyridostigmine Bromide
keywords: aging; atrial tachyarrhythmia; heart rate variability; hypertension; pyridostigmine; rat; sympathovagal balance