Effects of calcium channel blockers on sinoatrial conduction in the isolated and blood-perfused dog atrium.
Our previous study demonstrated that class I antiarrhythmics (fast sodium channel blockers) increased sinoatrial conduction time (SACT) in a dose-related fashion, indicating that a fast sodium current might play an important role in sinoatrial conduction. To assess a role of a slow calcium current in sinoatrial conduction, we examined effects of calcium channel blockers (diltiazem, verapamil, AQ-A 39, dilazep and bepridil) on SACT estimated by the constant atrial pacing in addition to on sinus cycle length (SCL) and on atrial developed tension (DT), using the isolated and blood-perfused dog right atrium. These calcium entry blockers except for bepridil were administered into the cannulated sinus node artery at an infusion rate of 0.2, 0.4 and 1.0 micrograms/min and bepridil at a rate of 0.6, 1.2 and 3.0 micrograms/min. The calcium antagonistic agents produced a dose-dependent decrease in DT and increase in SCL. The observed order of depression of inotropism was verapamil greater than diltiazem greater than bepridil = dilazep greater than AQ-A 39, while the order of negative chronotropism was diltiazem greater than verapamil greater than AQ-A 39 greater than dilazep greater than bepridil. However, as to dromotropism none of the five drugs exerted significant influences on SACT. From the previous and present results it is concluded that the fast sodium current may be predominantly important in sinoatrial conduction.
D000818:Animals; D015764:Bepridil; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004109:Dilazep / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D054833:Isoindoles; D009200:Myocardial Contraction / Q000187:drug effects; D010797:Phthalimides / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D054833:Isoindoles; D010797:Phthalimides; D011759:Pyrrolidines; D015764:Bepridil; D014700:Verapamil; D004110:Diltiazem; D004109:Dilazep; C030532:falipamil