OVINE DESIPRAMINE ANTIBODY FRAGMENTS REVERSE DESIPRAMINE CARDIOVASCULAR TOXICITY IN THE RAT

Study objective: To develop a model of severe desipramine cardiovascul ar toxicity and to determine whether partial neutralization of the ant igen by desipramine-specific Fab antibody fragments ameliorates its ca rdiovascular effects. Methods: We administered desipramine to rats unt il the QRS interval tripled in duration and mean arterial pressure (MA P) was less than 100 mm Hg. Animals were then assigned to one of six g roups: (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% neut ralization treatment), (4) 9.6% desipramine Fab (infusion of ovine des ipramine 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 demon strated slow and incomplete improvement. Ani mals in groups 4 through 6 showed improvement in QRS-interval duration and heart rate within 4 minutes (P<.05) compared with untreated anima ls. A dose-response relationship was evident; animals given the highes t dose of desipramine-specific Fab showed the greatest improvement. Co nclusion: Partial neutralization of desipramine by specific Fab fragme nts produces rapid improvement of QRS-interval duration and heart rate in a rat model of severe desipramine toxicity.