Ovine desipramine antibody fragments reverse desipramine cardiovascular toxicity in the rat.
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<.05) compared with untreated animals. A dose-response relationship was evident; animals given the highest dose of desipramine-specific Fab showed the greatest improvement.


CONCLUSIONS
Partial neutralization of desipramine by specific Fab fragments produces rapid improvement of QRS-interval duration and heart rate in a rat model of severe desipramine toxicity.
Dart
R C
RC
Department of Surgery, University of Arizona, Tucson, USA.
Sidki
A
A
Sullivan
J B
JB
Egen
N B
NB
Garcia
R A
RA
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000633:toxicity*; D001794:Blood Pressure; D003891:Desipramine / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007128:Immunoglobulin Fragments / Q000494:pharmacology; D007167:Immunotherapy; D008297:Male; D011041:Poisoning / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep
D000929:Antidepressive Agents, Tricyclic; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D003891:Desipramine