Verapamil Prevents Stretch-Induced Shortening of Atrial Effective Refractory Period in Langendorff-Perfused Rabbit Heart

Verapamil Prevents Stretch‐Induced AERP Shortening. Introduction: Atrial dilation and rapid pacing reduce atrial effective refractory periods (AERPs), thereby increasing the susceptibility to sustained atrial fibrillation (AF) in Langendorff‐perfused rabbit hearts. It is unclear whether similar pathophysiologic mechanisms are operative in short‐term electrophysiologic changes caused by dilation and rapid pacing. Therefore, we analyzed whether both forms of short‐term electrophysiologic changes are similarly affected by pharmacologic interventions acting on different potential mechanisms underlying these changes. Methods and Results: Thirty Langendorff‐perfused rabbit hearts underwent a protocol with stepwise increase of intra‐atrial pressure from 0 to 12 cmH2O followed by 10 minutes of rapid pacing at 4 cmH2O. The protocol was repeated after addition of glibenclamide (10 μ mol/L, n = 7), cariporide (1 μ mol/L, n = 7), or verapamil (1 μ mol/L, n = 9). In the basal state, increase of intra‐atrial pressure from 0 to 12 cmH2O decreased AERPs from 85 ± 11 to 55 ± 9 msec (P < 0.01), rapid pacing at low intra‐atrial pressure (4 cmH2O) decreased AERP to a similar extent, from 81 ± 11 to 60 ± 10 (P < 0.01). At higher intra‐atrial pressure, decrease of AERP was more pronounced (10 cmH2O: 37 ± 2 msec) (n = 7). Addition of verapamil decreased basal AERP from 86 ± 10 msec to 68 ± 11 msec (P < 0.05). Short‐term electrophysiologic changes due to atrial dilation were abolished; changes due to rapid pacing were reduced but still present. Glibenclamide and cariporide had no significant effect. Conclusion: Langendorff‐perfused rabbit heart is a suitable model for studying short‐term electrophysiologic changes due to both rapid pacing and atrial dilation. AERPs are shortened to a similar extent by both mechanisms, whereas a combination of the two leads to more pronounced AERP reduction. Calcium overload plays a crucial role in short‐term electrophysiologic changes caused by atrial dilation, whereas atrial ischemia or acidosis has no significant impact.