Pharmacologic Cardioversion of Chronic Atrial Fibrillation in the Goat by Class IA, IC, and III Drugs

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Abstract
Recently, we reported that repetitive induction of atrial fibrillation (AF) in the goat causes electrical remodeling of the atria leading to the development of sustained AF. The aim of the present study was to compare Class IA, IC, and III drugs in their ability to cardiovert chronic AF in remodeled atria. In 16 goats with sustained AF, hydroquinidine (HQ), cibenzoline (Ci), flecainide (FI), and d-sotalol (dS) were infused. HQ, Ci, Fl, and dS restored sinus rhythm (SR) in 83%, 91%, 67%, and 92% of the cases, while adverse drug effects occurred in 17%, 36%, 56%, and 8%. Prior to restoration of SR, AF cycle length prolonged by 68%, 103%, 53%, and 20%, respectively. The QRS width increased by 14%, 64%, and 58% (HQ, Ci, and Fl), and remained unchanged by administration of dS. RR intervals were slightly prolonged by HQ, Ci, and Fl, and markedly prolonged by dS (48%). The QT interval was moderately prolonged by HQ, Ci, and Fl, and considerably by dS (34%). QTc was only slightly prolonged by each of the drugs. Directly after cardioversion of AF, the atrial refractory period was 87+/-29 (HQ), 119+/-32 (Ci), 66+/-10 (Fl), and 73+/-18 msec (dS) (control: 146+/-18 msec). Atrial conduction velocity was 85+/-6, 71+/-11, 86+/-12, and 110+/-11 cm/sec compared with a control value of 116+/-10 cm/sec. Because directly after cardioversion the atrial wavelength was still very short (5.7 to 8.4 cm), the vulnerability for AF was still very high, and a single premature beat reinduced AF in 71% (Ci) to 100% (HQ, Fl, and dS) of the cases. In a goat model of sustained AF, Class IA, IC, and III drugs restored sinus rhythm in 67% to 92% of the cases. However, after cardioversion, the atrial wavelength was still abnormally short, and AF was readily inducible in 71% to 100% of the cases.