title: Spontaneous reversibility of catecholamine-induced cardiotoxicity in rats.
abstract: In order to evaluate the chronic in vivo effects of excessive catecholamine levels, and the potential for spontaneous reversibility of these effects, we employed a chronic two-week infusion of epinephrine in rats. Epinephrine infusion resulted in myocyte hypertrophy, left ventricular fibrotic degenerative changes, diminished response to adrenergic stimuli, and enhanced left ventricular papillary contractile responses to calcium. Two weeks after cessation of the epinephrine infusion, left ventricular fibrotic degenerative changes were reduced, and responses to adrenergic stimuli were partially restored. However, myocyte hypertrophy and the enhanced responses to calcium persisted in these animals. This study indicates the potential for spontaneous reversal of some of epinephrine's toxic effects, and further implies that the loss in adrenergic sensitivity in epinephrine-treated animals may be a desensitization phenomenon, while the alterations in calcium response are less readily reversed.
authors.affiliation: Department of Medicine, Stanford University, CA 94305, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Deisher
authors.forename: R
authors.initials: R
authors.lastname: Ginsburg
authors.forename: M B
authors.initials: MB
authors.lastname: Fowler
authors.forename: M E
authors.initials: ME
authors.lastname: Billingham
authors.forename: M R
authors.initials: MR
authors.lastname: Bristow
mesh_terms: D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects; D015918:Infusion Pumps, Implantable; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012075:Remission, Spontaneous
chemical_list: D015220:Calcium Channels; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D004837:Epinephrine