Antidotal treatment of the acute cardiovascular toxicity of verapamil.
Rats anaesthetized with pentobarbital and ventilated artificially were infused with 0.15 mg/kg/min. verapamil; without antidotal treatment, they died after 51.1+/-7.1 min. The survival time more than trebled upon an additional infusion with calcium chloride, epinephrine, isoprenaline, orciprenaline or prenalterol and nearly doubled upon administration of a plasma expander. It was not increased, however, by treatment with angiotensin or atropine. The infusion of verapamil declined the arterial blood pressure by 75%, and heart rate, cardiac output and peripheral resistance by about 50%; in the ECG, sinus bradycardia followed by AV-dissociation with nodal rhythm occurred. All antidotes that raised the lethal dose of verapamil increased the cardiac output. Calcium and the sympathomimetics with alpha-adrenergic activity also counteracted the verapamil-induced hypotension. Calcium did not influence the ECG alterations produced by verapamil, while the sympathomimetics restored the sinus rhythm or accelerated the nodal pacemaker. Calcium, epinephrine and isoprenaline also antagonized the strong decrease of left-ventricular dp/dt max. induced by verapamil. In conclusion, calcium as well as sympathomimetic amines are potent antidotes against the cardiovascular toxicity of verapamil, the latter being superior to calcium in their ability to improve pacemaker activity and AV-conduction.
D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000188:drug therapy*; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014700:Verapamil / Q000037:antagonists & inhibitors / Q000506:poisoning*
D000931:Antidotes; D014700:Verapamil