title: A comparison of combined amrinone and glucagon therapy to glucagon alone for cardiovascular depression associated with propranolol toxicity in a canine model.
abstract: Multiple inotropic agents may be required to improve hypotension associated with beta-blocker toxicity. This study compared combined amrinone and glucagon therapy to glucagon alone and saline control for the treatment of propranolol-induced cardiovascular depression in a canine model. Six animals were pretreated with 10 mg/kg of propranolol intravenously (i.v.), which resulted in significant depression in heart rate (HR), cardiac output (CO), mean arterial pressure (MAP), and maximal left ventricular change in pressure over time (dP/dt max) (P < .0001). Each canine received i.v. amrinone (4 mg/kg) plus glucagon (20 micrograms/kg) therapy during a 2-minute period after propranolol infusion was completed. Cardiovascular parameters were monitored at 1, 6, 11, 21, and 31 minutes after treatment was rendered. Results were compared with those of a previous study, consisting of six animals that received glucagon therapy alone (20 mg/kg) and six controls (normal saline only) in an identical protocol. The addition of i.v. amrinone to glucagon therapy did not increase significantly, HR, CO, stroke volume, or dP/dt max compared with glucagon alone. Total systemic peripheral resistance was reduced significantly during 31 minutes of observation after the administration of combined therapy compared with the control; glucagon alone also reduced systemic peripheral resistance at 1 and 6 minutes. At all time periods except 1 minute of observation there was a significant reduction in MAP when comparing combined therapy with that of glucagon therapy alone. In this model, the addition of amrinone to glucagon therapy seems to have a detrimental effect on the ability of glucagon to increase MAP resulting from propranolol toxicity.
authors.affiliation: Department of Emergency Medicine, Georgetown University, Washington, DC 20007.
authors.forename: J N
authors.initials: JN
authors.lastname: Love
authors.forename: J A
authors.initials: JA
authors.lastname: Leasure
authors.forename: D J
authors.initials: DJ
authors.lastname: Mundt
mesh_terms: D000676:Amrinone / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003864:Depression, Chemical; D004285:Dogs; D004359:Drug Therapy, Combination; D005934:Glucagon / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy*; D011433:Propranolol / Q000009:adverse effects*
chemical_list: D005934:Glucagon; D011433:Propranolol; D000676:Amrinone