Background Nifekalant may prevent atrial fibrillation (AF) and possibly be useful in treatment of atrial tachyarrhythmia in patients with severe heart failure. This study investigated the electophysiologic effect of nifekalant on the acute atrial remodeling in rapid atrial pacing (RAP) model of canine.Methods Twelve mongrel dogs subjected to rapid stimulation (400 beats/min) at left atrial appendage (LAA)for 24 hours, were randomized into the control group (rapid pacing only, n=6) and the nifekalant group (intravenous nifekalant therapy immediately after RAP, n=6). Atrial electrophysiological parameters were measured in right atrium, coronary sinus, LAA, posterior wall of left atrium (PWLA) and left superior pulmonary vein (LSPV), before and after the RAP.Results In the control group, the effective refractory periods (ERP) were shortened greatly at all sites, paced dogs had substantially shorter ERPs in the high right atrium, LAA, and LSPV, but fewer changes in the PWLA,the coefficient variation of ERP (COV ERP) was increased significantly. After rapid atrial stimulation, the inducibility of AF increased significantly [induction number: pre-RAP vs post-RAP, 1.00± 0.89 vs 8.17 ± 2.79,P＜0.01; duration of AF: pre-RAP vs post-RAP, (450.34± 362.59) ms vs (9975.77 ±4376.99) ms, P＜0.01]. In the nifekalant group, although the ERPs were prolonged at all sites compared with those in pre-RAP state, only the value at LSPV differed significantly from that in pre-RAP state [pre-RAP vs post-RAP, (102.50±5.24) ms vs (132.51 ±5.20) ms, P＜0.01]; the COV ERP did not change statistically in this group. The inducibility of AF slightly increased but insignificantly after pacing [induction number: pre-RAP vs post-RAP, 0.83 ±0.75 vs 1.67±0.82, P=0.19; duration of AF: pre-RAP vs post-RAP, (378.67±317.88) ms vs (1124.08±1109.77) ms,P=0.06]. Conduction time values did not alter significantly in either of the two groups after RAP.Conclusions In canine RAP model, nifekalant inhibited ERP shortening and ERP heterogeneity increasing,decreased AF induction. Nifekalant can reverse acute electrical remodeling effect in this model.