Cellular mechanism of pituitary adenylate cyclase-activating polypeptide-induced atrial tachyarrhythmia in canine isolated arterially perfused right atria

Clin Exp Pharmacol Physiol. 2003 Dec;30(12):937-42. doi: 10.1111/j.1440-1681.2003.03940.x.

Abstract

1. Pituitary adenylate cyclase-activating polypeptide (PACAP) induces atrial tachyarrhythmia (AT). However, the cellular mechanism responsible for this remains unclear. 2. In six canine isolated arterially perfused right atria, high-resolution optical mapping techniques were used to measure action potentials during control conditions and after PACAP injection (1 nmol). 3. During steady state pacing at a cycle length of 300 msec, the action potential duration was shorter during PACAP than during control (P < 0.001). In addition, maximum repolarization gradients during PACAP (4 +/- 1 msec/mm) were similar to those during control (5 +/- 1 msec/mm; n = 6). Transmural repolarization gradients were also similar between the two groups. 4. After PACAP, AT was easily initiated with a single premature extrastimulus and was associated with a focal pattern of activation. However, AT was not initiated by a single premature stimulus during control. 5. In conclusion, the PACAP-induced AT is associated with a focal pattern of activation that is independent of local repolarization gradients. These data suggest that increased dispersion of repolarization is not necessarily required for the induction of AT.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Cardiac Pacing, Artificial / methods
  • Dogs
  • Electrophysiologic Techniques, Cardiac
  • Endocardium / drug effects
  • Endocardium / physiology
  • Heart Atria / drug effects
  • Heart Atria / physiopathology
  • Injections, Intra-Arterial
  • Male
  • Neuropeptides / administration & dosage
  • Neuropeptides / adverse effects*
  • Neuropeptides / chemistry
  • Pericardium / drug effects
  • Pericardium / physiology
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Refractory Period, Electrophysiological / drug effects
  • Tachycardia / chemically induced*
  • Tachycardia / physiopathology
  • Time Factors

Substances

  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide