title: Effect of autonomic blocking agents on the respiratory-related oscillations of ventricular action potential duration in humans.
abstract: Ventricular action potential duration (APD) is an important component of many physiological functions including arrhythmogenesis. APD oscillations have recently been reported in humans at the respiratory frequency. This study investigates the contribution of the autonomic nervous system to these oscillations. In 10 patients undergoing treatment for supraventricular arrhythmias, activation recovery intervals (ARI; a conventional surrogate for APD) were measured from multiple left and right ventricular (RV) endocardial sites, together with femoral artery pressure. Respiration was voluntarily regulated and heart rate clamped by RV pacing. Sympathetic and parasympathetic blockade was achieved using intravenous metoprolol and atropine, respectively. Metroprolol reduced the rate of pressure development (maximal change in pressure over time): 1,271 (± 646) vs. 930 (± 433) mmHg/s; P < 0.01. Systolic blood pressure (SBP) showed a trend to decrease after metoprolol, 133 (± 21) vs. 128 (± 25) mmHg; P = 0.06, and atropine infusion, 122 (± 26) mmHg; P < 0.05. ARI and SBP exhibited significant cyclical variations (P < 0.05) with respiration in all subjects with peak-to-peak amplitudes ranging between 0.7 and 17.0 mmHg and 1 and 16 ms, respectively. Infusion of metoprolol reduced the mean peak-to-peak amplitude [ARI, 6.2 (± 1.4) vs. 4.4 (± 1.0) ms, P = 0.008; SBP, 8.4 (± 1.6) vs. 6.2 (± 2.0) mmHg, P = 0.002]. The addition of atropine had no significant effect. ARI, SBP, and respiration showed significant coupling (P < 0.05) at the breathing frequency in all subjects. Directed coherence from respiration to ARI was high and reduced after metoprolol infusion [0.70 (± 0.17) vs. 0.50 (± 0.23); P < 0.05]. These results suggest a role of respiration in modulating the electrophysiology of ventricular myocardium in humans, which is partly, but not totally, mediated by β-adrenergic mechanisms.
authors.affiliation: Department of Mechanical Engineering, University College London, London, UK;
authors.forename: Stefan
authors.initials: S
authors.lastname: van Duijvenboden
authors.affiliation: Department of Mechanical Engineering, University College London, London, UK;
authors.forename: Ben
authors.initials: B
authors.lastname: Hanson
authors.affiliation: Department of Cardiology, Guy's and St. Thomas's Hospital, London, UK; and.
authors.forename: Nick
authors.initials: N
authors.lastname: Child
authors.affiliation: Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Michele
authors.initials: M
authors.lastname: Orini
authors.affiliation: Department of Cardiology, Guy's and St. Thomas's Hospital, London, UK; and.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Rinaldi
authors.affiliation: Department of Cardiology, Guy's and St. Thomas's Hospital, London, UK; and.
authors.forename: Jaswinder S
authors.initials: JS
authors.lastname: Gill
authors.affiliation: Institute of Cardiovascular Science, University College London, London, UK p.taggart@ucl.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Taggart
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001340:Autonomic Nerve Block; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D015656:Respiratory Mechanics; D013617:Tachycardia, Supraventricular / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D001285:Atropine; D008790:Metoprolol
keywords: cardiac electrophysiology; parasympathetic blockade; respiration; β-adrenergic blockade