Effect of autonomic blocking agents on the respiratory-related oscillations of ventricular action potential duration in humans

Am J Physiol Heart Circ Physiol. 2015 Dec 15;309(12):H2108-17. doi: 10.1152/ajpheart.00560.2015. Epub 2015 Oct 16.

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.

Keywords: cardiac electrophysiology; parasympathetic blockade; respiration; β-adrenergic blockade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Adrenergic beta-Antagonists / pharmacology
  • Aged
  • Anti-Arrhythmia Agents / pharmacology
  • Atropine / pharmacology
  • Autonomic Nerve Block*
  • Blood Pressure / drug effects
  • Electrocardiography / drug effects
  • Female
  • Heart Rate / drug effects
  • Heart Ventricles / drug effects*
  • Heart Ventricles / physiopathology
  • Humans
  • Male
  • Metoprolol / pharmacology
  • Middle Aged
  • Muscarinic Antagonists / pharmacology
  • Parasympatholytics / pharmacology
  • Respiratory Mechanics*
  • Tachycardia, Supraventricular / physiopathology
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Right / drug effects

Substances

  • Adrenergic beta-Antagonists
  • Anti-Arrhythmia Agents
  • Muscarinic Antagonists
  • Parasympatholytics
  • Atropine
  • Metoprolol