Ovine Desipramine Antibody Fragments Reverse Desipramine Cardiovascular Toxicity in the Rat

Study objective: 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. Methods: We administered desipramine to rats until the QRS interval...

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Bibliographic Details
Published in:Annals of emergency medicine 1996-03, Vol.27 (3), p.309-315
Main Authors: Dart, Richard C, Sidki, Ahmed, Sullivan, John B, Egen, Ned B, Garcia, Ray A
Format: Article
Language:English
Subjects:
Animals
Antidepressive Agents, Tricyclic - toxicity
Biological and medical sciences
Blood Pressure
Desipramine - toxicity
Drug toxicity and drugs side effects treatment
Heart - drug effects
Heart Conduction System - drug effects
Heart Rate
Immunoglobulin Fab Fragments - pharmacology
Immunoglobulin Fragments - pharmacology
Immunotherapy
Male
Medical sciences
Pharmacology. Drug treatments
Poisoning - drug therapy
Rats
Rats, Sprague-Dawley
Sheep
Toxicity: cardiovascular system
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Summary:Study objective: 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. Methods: 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. Results: 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
ISSN:0196-0644
1097-6760
DOI:10.1016/S0196-0644(96)70265-2