Ovine desipramine antibody fragments reverse desipramine cardiovascular toxicity in the rat

Annals of Emergency Medicine
R C DartR A Garcia

Abstract

To develop a model of severe desipramine cardiovascular toxicity and to determine whether partial neutralization of the antigen by desipramine-specific Fab antibody fragments ameliorates its cardiovascular effects. We administered desipramine to rats until the QRS interval tripled in duration and mean arterial pressure (MAP) was less than 100 mm Hg. Animals were then assigned to one of six groups: (1) no treatment, (2) normal saline solution control treatment (.9% NaCl infusion equal to the volume of Fab infusion), (3) nonimmune Fab control treatment (infusion of Fab equal to that in the 9.6% neutralization treatment), (4) 9.6% desipramine Fab (infusion of ovine desipramine Fab equal to 9.6% of an equimolar neutralization), (5) 19.2% desipramine Fab, and (6) 30.0% desipramine Fab. QRS-interval duration, heart rate, and MAP were recorded for 60 minutes. Animals in groups 1 through 3 demonstrated slow and incomplete improvement. Animals in groups 4 through 6 showed improvement in QRS-interval duration and heart rate within 4 minutes (P<.05) compared with untreated animals. A dose-response relationship was evident; animals given the highest dose of desipramine-specific Fab showed the greatest improvement. Partial neutralization of...Continue Reading

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Citations

Jul 1, 1997·Critical Care Clinics·D D Vernon, M C Gleich
Oct 3, 2001·Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine·R E HillR C Dart
Mar 21, 2007·Critical Care : the Official Journal of the Critical Care Forum·Frédéric J BaudPascal Leprince
Jun 8, 2010·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Nilüfer Yalindağ-OztürkBrett Giroir
Oct 20, 2015·Resuscitation·Anatolij TruhlářUNKNOWN Cardiac arrest in special circumstances section Collaborators
Jun 6, 2006·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Kennon HeardSuzanne B Ward
Nov 18, 1997·Human & Experimental Toxicology·C BismuthJ M Scherrmann
Nov 24, 2004·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Robert J Flanagan, Alison L Jones

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