Treatment of verapamil toxicity in intact dogs.
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 less than 0.001), heart rate (HR) from 85 +/- 4 to 57 +/- 3 beats/min (P less than 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 less than 0.001), mean aortic pressure (AO) from 77 +/- 4 to 38 +/- 2 mm Hg (P less than 0.001) and stroke volume from 39 +/- 3 to 28 +/- 2 ml/beat (P less than 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 micrograms/kg per min) produced no changes except a small increase in AO while very high dose phenylephrine (300 micrograms/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 less than 0.001), CO (P less than 0.01), and LV dP/dt (P less than 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.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000627:therapeutic use; D000818:Animals; D001285:Atropine / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002122:Calcium Chloride / Q000627:therapeutic use; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004298:Dopamine / Q000627:therapeutic use; D004837:Epinephrine / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000627:therapeutic use; D009638:Norepinephrine / Q000627:therapeutic use; D010656:Phenylephrine / Q000627:therapeutic use; D013268:Stimulation, Chemical; D013318:Stroke Volume / Q000187:drug effects; D014700:Verapamil / Q000633:toxicity*
D000631:Aminopyridines; D010656:Phenylephrine; D001285:Atropine; D015761:4-Aminopyridine; D014700:Verapamil; D007545:Isoproterenol; D002122:Calcium Chloride; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine