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


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.


CONCLUSIONS
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
M
Department of Internal Medicine and Cardiology, Rheinisch-Westfailische Technische, Hochschule Aachen, Germany. mzar@pcserver.mk1.rwth-aachen.de
Stellbrink
C
C
Athanatou
E
E
Robert
J
J
Schotten
U
U
Hanrath
P
P
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000209:etiology; D016275:Atrial Function / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial / Q000379:methods; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects*; D013450:Sulfones / Q000494:pharmacology; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D006146:Guanidines; D013450:Sulfones; C093373:cariporide; D014700:Verapamil; D005905:Glyburide