Published Online
on June 30, 2003

A more recent version of this article appeared on July 22, 2003

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Submitted on January 27, 2003
Revised on April 1, 2003
Accepted on April 4, 2003

Altered Atrial Electrical Restitution and Heterogeneous Sympathetic Hyperinnervation in Hearts With Chronic Left Ventricular Myocardial Infarction. Implications for Atrial Fibrillation

Yasushi Miyauchi MD, Shengmei Zhou MD, Yuji Okuyama MD, Mizuho Miyauchi MD, Hideki Hayashi MD, Akira Hamabe MD, Michael C. Fishbein MD, William J. Mandel MD, Lan S. Chen MD, Peng-Sheng Chen MD, and Hrayr S. Karagueuzian PhD^*

From the Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center; Department of Pathology and Laboratory Medicine, University of California Los Angeles School of Medicine (M.C.F.); and The Children's Hospital, (L.-S.C.) Los Angeles, Calif.

^* To whom correspondence should be addressed. E-mail: Hrayr.Karagueuzian{at}cshs.org.

Background--The substrates for the increased incidence of atrial fibrillation (AF) in hearts with chronic left ventricular myocardial infarction (MI) remain poorly defined. We hypothesized that chronic MI is associated with atrial electrical and neural remodeling that enhances AF vulnerability.

Methods and Results--We created MI in 8 dogs by permanent occlusion of the left anterior descending (LAD) coronary artery. Seven dogs (3 with thoracotomy) that had no LAD occlusion served as controls. Eight weeks after surgery, the incidence and duration of pacing-induced AF in the open chest anesthetized state were significantly (P<0.05) higher in the MI than in control dogs. Multisite biatrial monophasic action potential (MAP) recordings showed increased heterogeneity of MAP duration (MAPD) and MAPD restitution slope. AF in the MI groups was preceded by significantly higher MAPD (P<0.01) and MAP amplitude (P<0.05) alternans in both atria compared with controls. Epicardial mapping using 1792 bipolar electrodes (1-mm spatial resolution) showed multisite wavebreaks of the paced wavefronts leading to AF in MI but not in control dogs. Multiple wavelets in MI dogs were associated with significantly higher incidence and longer duration of AF compared with control. The density of biatrial tyrosine hydroxylase (TH) and growth-associated protein43 (GAP43) nerves were 5- to 8-fold higher and were more heterogeneous in MI compared with control dogs.

Conclusions--Chronic ventricular MI with no atrial involvement causes heterogeneous alteration of atrial electrical restitution and atrial sympathetic hyperinnervation that might provide important substrates for the observed increased AF vulnerability.

Key words: nervous system • myocardial infarction • remodeling • atrium • fibrillation

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