The treatment of verapamil toxicity was examined in lightly sedated dogs. Verapamil, administered as a bolus (0.72 mg/kg) followed by a continuous infusion (0.11 mg/kg per min), decreased cardiac output (CO) from 3.1 ± 0.1 to 1.7 ± 0.1 liter/min (P < 0.001), heart rate (HR) from 85 ± 4 to 57 ± 3 beats/min (P < 0.001), left ventricular derivative of pressure with respect to time (LV dP/dt) from 2,085 ± 828 to 783 ± 78 mm Hg/s (P < 0.001), mean aortic pressure (AO) from 77 ± 4 to 38 ± 2 mm Hg (P < 0.001) and stroke volume from 39 ± 3 to 28 ± 2 ml/beat (P < 0.01). In verapamil-toxic animals isoproterenol increased HR, CO, LV dP/dt, and AO; calcium chloride increased LV dP/dt and AO; norepinephrine, epinephrine, and dopamine increased CO, AO, and LV dP/dt, atropine increased HR, CO, and AO. Phenylephrine (13-55 μg/kg per min) produced no changes except a small increase in AO while very high dose phenylephrine (300 μg/kg per min) increased AO, CO, and LV dP/dt. 4-Aminopyridine (4-AP) increased HR, CO, LV dP/dt, and AO. When administered prior to verapamil, 4-AP prevented the development of verapamil toxicity as shown by the significantly higher AO (P < 0.001), CO (P < 0.01), and LV dP/dt (P < 0.01) when 4-AP followed by verapamil was compared to verapamil alone. In conclusion, there does not appear to be a single specific therapy for verapamil toxicity, however it can be partially corrected by presently available pharmacologic therapy and 4-AP.
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