Tetrandrine Prevents Tachycardia-induced Acute Atial Electrical Remodeling

Objective:This study to investigated the effect of tachycardia-induced on atrial electrophysiological characteristics; To assessed the effects of the both T and L-type Ca2＋channel blocker tetrandrine on tachycardia-induced atrial electrical remodeling.Methods: In twenty-four New Zealand big ear rabbits paced with maximal atrial capture rate for 8h were randomly divided into saline group (n=8) and verapamil group (n=8) and tetrandrine group (n=8). The infusion of saline, tetrandrine, verapamil was initiated 30 minutes before rapid pacing and continued throughout the study. The atrial effective refractory period (AERP) was measured with S1S2 programmed electrical stimulation at pre-tachycardia (after autonomic blockade), during tachycardia (0.5, 1, 2, 4, 6, 8 hours) and post-tachycardia (10min, 20min, 30min,60min). To determined the effective refractory period adaptating to rate (ERP-RA), the AERPs were measured in the right atrial appendage at 3 pacing cycle lengths (150,200,250 ms) respectively. The right atrialcular appendage tissue specimen was fixated and examined by electron microscope at last.Results: 1. In the saline group, AERP was significantly shortened after 0.5h of rapid atrial pacing(from 120.00±11.10, 128.13±12.80, 132.5±12.82ms to 110.63±11.116, 113.13±11.63, 115.00±10.69ms,P=0.000). The mimimum value of AERP150, AERP200, AERP250 occurred after 8 hour of rapid atrial pacing. The AERP recovered quickly with a return to within 96% of baseline after 10 minutes of post-tachycardia. However, in the tetrandrine and verapamil groups, shortening of the AERP after rapid pacing was completely inhibited. There was no significant difference in AERP shortening between the tetrandrine group and verapamil group. 2. Although ERP-RA was lost in the saline group after 0.5h of rapid atrial pacing (0.125vs 0.044, P＝0.000), this phenomenon was preserved in the tetrandrine and verapamil group. 3. Electron microscopic studies of right atricular appendage tissue demonstrated that mitochondrial swelling and accumulation of glycogen were observed in rabbits paced for 8 hours. The sarcoplasmic reticulum and nucleri were normal.Conclusion: 1. Short-term rapid atrial pacing reduces atrial electrical remodeling, which develops quickly after pacing and recovers quickly after the offset of rapid pacing. 2. Tetrandrine, a drug with L and T-type Ca2+ channel blocking properties, prevents electrophysiological remodeling by atrial tachycardia. 3. The ultrastructural changes may be observed after short-term atrial paing.