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-perfuse rabbit hearts underwent a protocol with stepwise increase of intra-atrial pressure from 0 to 12 cmH(2)O followed by 10 minutes of rapid pacing at 4 cmN(2)O. The protocol was repeated after addition of glibenclamide (10 mu mol/L, n = 7),cariporide (1 mu mol/L, n = 7), or verapamil (1 mu mol/L, n = 9). In the basal state, increase of intra-atrial pressure from 0 to 12 cmH(2)O decreased AERPs from 85 +/- 11 to 55 +/- 9 msec (P < 0.01), rapid pacing at low intra-atrial pressure (4 cmH(2)O) 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 cmH(2)O: 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-perfuse 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.