Concentration-dependent enhancement of junctional pacemaker activity by verapamil in man

The effects of verapamil on junctional and sinoatrial activity were studied in eight patients with third-degree atrioventricular block and stable junctional rhythms. After intravenous infusion of verapamil three steady-state levels were reached as follows: 34 +/- 16 (SS1), 68 +/- 30 (SS2), and 129 +/- 54 (SS3) ng/ml. At each steady-state level, spontaneous sinus and junctional cycle lengths, QT intervals, junctional recovery times after ventricular pacing, blood pressure, and circulating catecholamine concentrations were measured. These measurements were compared with observations made during an identical protocol (except for the exclusion of verapamil infusions) on a control day. No significant changes were detected in the spontaneous sinus or junctional cycle length, junctional recovery times at a fixed pacing cycle length, blood pressure, or circulating catecholamine concentrations during the control day. In response to verapamil, the mean junctional cycle length decreased from a baseline value of 1320 +/- 239 to 1254 +/- 210, 1199 +/- 214, 1069 +/- 151 msec at SS1, SS2, and SS3 (p less than .01). Sinus cycle length (msec) was unaffected or slightly lengthened from 749 +/- 165 at baseline to 821 +/- 222 at SS1, 831 +/- 222 at SS2, and 817 +/- 175 at SS3 (NS). Mean blood pressure, circulating catecholamine concentrations, and corrected QT intervals were also unchanged by verapamil. Verapamil enhanced junctional pacemaker activity in patients with third-degree atrioventricular block, suggesting that (1) these rhythms originate in cells that are not suppressed by the slow-channel antagonism of verapamil and (2) the acceleration of junctional activity seen in response to verapamil reflects a verapamil effect rather than toxicity.