Verapamil prevents stretch-induced shortening of atrial effective refractory period in langendorff-perfused rabbit heart.

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 cm H2O followed by 10 minutes of rapid pacing at 4 cm H2O. The protocol was repeated after addition of glibenclamide (10 micromol/L, n = 7), cariporide (1 micromol/L, n = 7), or verapamil (1 micromol/L, n = 9). In the basal state, increase of intra-atrial pressure from 0 to 12 cm H2O 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 cm H2O: 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.

Zarse M ，Stellbrink C ，Athanatou E ，Robert J ，Schotten U ，Hanrath P ... -  《JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY》

Atrial electrical remodeling by rapid pacing in the isolated rabbit heart: effects of Ca++ and K+ channel blockade.

Wood MA ，Caponi D ，Sykes AM ，Wenger EJ ... -  《JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY》

Effects of atrial dilatation on refractory period and vulnerability to atrial fibrillation in the isolated Langendorff-perfused rabbit heart.

Ravelli F ，Allessie M 《CIRCULATION》

Verapamil suppresses the inhomogeneity of electrical remodeling in a canine long-term rapid atrial stimulation model.

Moriguchi M ，Niwano S ，Yoshizawa N ，Kojima J ，Inuo K ，Izumi T ... -  《PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY》

Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats: roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation.

Wijffels MC ，Kirchhof CJ ，Dorland R ，Power J ，Allessie MA ... -  《CIRCULATION》