Cellular mechanism of pituitary adenylate cyclase-activating polypeptide-induced atrial tachyarrhythmia in canine isolated arterially perfused right atria.
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.
Hirose
Masamichi
M
Department of Molecular Pharmacology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan. hirose@sch.md.shinshu-u.ac.jp
Chiba
Shigetoshi
S
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods; D004285:Dogs; D022062:Electrophysiologic Techniques, Cardiac; D004699:Endocardium / Q000187:drug effects / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D007269:Injections, Intra-Arterial; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D010496:Pericardium / Q000187:drug effects / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013610:Tachycardia / Q000139:chemically induced* / Q000503:physiopathology; D013997:Time Factors
D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide