title: A comparison of amrinone and glucagon therapy for cardiovascular depression associated with propranolol toxicity in a canine model.
abstract: This study's objective is to evaluate the ability of glucagon and amrinone to reverse propranolol induced cardiovascular depression in a canine model, compared to a control of normal saline. The study design included 18 animals which received intravenous propranolol (10 mg/kg) resulting in significant depression in heart rate, cardiac output, mean arterial pressure, maximal ventricular dP/dt and stroke volume. Each canine was randomly assigned to one of three treatment groups; controls (normal saline only), glucagon (20 micrograms/kg bolus) and amrinone (4 mg/kg bolus). Cardiovascular parameters were monitored at 1, 6, 11, 21 and 31 min after treatment was rendered. Multiple comparison procedures at each time period controlled the overall alpha-level at .05. Compared to control animals, both amrinone and glucagon were effective in reversing propranolol-induced depression of dP/dtmax at 6 and 11 min for glucagon and 11 min for amrinone and cardiac output at 1, 6 and 11 min for glucagon and 1 min for amrinone. Amrinone and glucagon significantly increased stroke volume over control values at 1 min and tended to do so at the remaining time periods. The two days caused a similar degree of arteriolar vasodilation which was significantly greater than that seen in control animals at 1 and 6 min. Beta blocker induced bradycardia did not respond significantly to amrinone while glucagon induced a tachycardia which is unique to canines. It is concluded that in this canine model, amrinone appears to be an effective therapeutic alternative to glucagon for reversing depressed dP/dtmax, cardiac output and stoke volume induced by propranolol toxicity. Unlike glucagon, amrinone appears to lack positive chronotropic activity which may limit its clinical utility in the treatment of beta blocker overdose.
authors.affiliation: Georgetown University, Washington, DC.
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
authors.forename: T G
authors.initials: TG
authors.lastname: Janz
mesh_terms: D000676:Amrinone / Q000627:therapeutic use*; D000818:Animals; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000188:drug therapy*; D003864:Depression, Chemical; D004285:Dogs; D062787:Drug Overdose; D004562:Electrocardiography; D005934:Glucagon / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D011433:Propranolol / Q000506:poisoning*; D011897:Random Allocation
chemical_list: D005934:Glucagon; D011433:Propranolol; D000676:Amrinone