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

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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.
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Keywords: atrial tachyarrhythmia; autonomic nervous system; effective refractoriness; pituitary adenylate cyclase-activating polypeptide

Document Type: Research Article

Affiliations: Department of Molecular Pharmacology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

Publication date: December 1, 2003

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