Heart Rhythm
Volume 5, Issue 8 , Pages 1170-1177, August 2008

Intracellular calcium dynamics and acetylcholine-induced triggered activity in the pulmonary veins of dogs with pacing-induced heart failure

  • Chung-Chuan Chou, MD

      Affiliations

    • Second Section of Cardiology, Department of Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
    • ,
  • Bich Lien Nguyen, MD

      Affiliations

    • Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles California
    • ,
  • Alex Y. Tan, MD

      Affiliations

    • Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles California
    • ,
  • Po-Cheng Chang, MD

      Affiliations

    • Second Section of Cardiology, Department of Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
    • ,
  • Hui-Ling Lee, MD

      Affiliations

    • Department of Anesthesia, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
    • ,
  • Fun-Chung Lin, MD

      Affiliations

    • Second Section of Cardiology, Department of Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
    • ,
  • San-Jou Yeh, MD

      Affiliations

    • Second Section of Cardiology, Department of Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
    • ,
  • Michael C. Fishbein, MD

      Affiliations

    • Division of Anatomical Pathology, Department of Pathology, UCLA, Los Angeles, California
    • ,
  • Shien-Fong Lin, PhD

      Affiliations

    • Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
    • ,
  • Delon Wu, MD

      Affiliations

    • Second Section of Cardiology, Department of Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
    • ,
  • Ming-Shien Wen, MD

      Affiliations

    • Second Section of Cardiology, Department of Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
    • ,
  • Peng-Sheng Chen, MD, FHRS

      Affiliations

    • Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
    • Corresponding Author InformationAddress correspondence: Dr. Peng-Sheng Chen, Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, 1801 N. Senate Avenue, E475, Indianapolis, Indiana 46202.

Received 24 November 2007; accepted 9 April 2008. published online 14 April 2008.

Background

Heart failure increases autonomic nerve activities and changes intracellular calcium (Cai) dynamics.

Objective

The purpose of this study was to investigate the hypothesis that abnormal Cai dynamics are responsible for triggered activity in the pulmonary veins (PVs) during acetylcholine infusion in a canine model of heart failure.

Methods

Simultaneous optical mapping of Cai and membrane potential was performed in isolated Langendorff-perfused PV–left atrial (LA) preparations from nine dogs with ventricular pacing-induced heart failure. Mapping was performed at baseline, during acetylcholine (1 μmol/L) infusion (N = 9), and during thapsigargin and ryanodine infusion (N = 6).

Results

Acetylcholine abbreviated the action potential. In four tissues, long pauses were followed by elevated diastolic Cai, late phase 3 early afterdepolarizations, and atrial fibrillation (AF). The incidence of PV focal discharges during AF was increased by acetylcholine from 2.4 ± 0.6 beats/s (N = 4) to 6.5 ± 2.2 beats/s (N = 8; P = .003). PV focal discharge and PV–LA microreentry coexisted in 6 of 9 preparations. The spatial distribution of dominant frequency demonstrated a focal source pattern, with the highest dominant frequency areas colocalized with PV focal discharge sites in 35 (95%) of 37 cholinergic AF episodes (N = 8). Thapsigargin and ryanodine infusion eliminated focal discharges in 6 of 6 preparations and suppressed the inducibility of AF in 4 of 6 preparations. PVs with focal discharge have higher densities of parasympathetic nerves than do PVs without focal discharges (P = .01), and periodic acid–Schiff (PAS)-positive cells were present at the focal discharge sites.

Conclusion

Cai dynamics are important in promoting triggered activity during acetylcholine infusion in PVs from pacing-induced heart failure. PV focal discharge sites have PAS-positive cells and high densities of parasympathetic nerves.

Keywords: Acetylcholine, Atrium, Calcium, Fibrillation, Heart failure, Mapping

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 This study was supported by CMRPG33016 to Dr. Chou, a Piansky Endowment to Dr. Fishbein, a Pauline and Harold Price Endowment and Medtronic-Zipes Endowment to Dr. Chen. This study was supported in part by an AHA Established Investigatorship Award and by NIH Grants P01-HL78931, R01-HL58533, 66389, 78932, and 71140.

 This manuscript was processed by a guest editor.

PII: S1547-5271(08)00421-9

doi:10.1016/j.hrthm.2008.04.009

Heart Rhythm
Volume 5, Issue 8 , Pages 1170-1177, August 2008

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