title: Desipramine pretreatment improves sympathetic remodeling and ventricular fibrillation threshold after myocardial ischemia.
abstract: Abnormal increase in sympathetic nerve sprouting was responsible for the ventricular arrhythmogenesis after myocardial infarction. This study investigated whether the norepinephrine transporter inhibitor, desipramine, can modulate sympathetic remodeling and ventricular fibrillation threshold (VFT) after myocardial ischemia-reperfusion. Rats were administered desipramine (0.8 mg/kg, i.v.) before or after myocardial ischemia. VFT, infarct size, tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43)-positive nerve fibers were measured after one week. The VFT of preischemic treatment group was 11.0 ± 2.65 V and significantly higher than that of control ischemic group (7.2 ± 1.30 V, P < 0.05). Infarct size in the preischemic treatment group (23.3 ± 2.4%) was significantly lower than that in the control ischemic group (30.8 ± 1.3%, P < 0.05) and the delayed application group (27.1 ± 2.6%, P < 0.05). The density of TH and GAP43-positive nerve fibers in the control ischemic group was significantly higher than that in the other three groups (P < 0.05). The density of nerve fibers improved after desipramine treatment. Moreover, there was a negative correlation between the VFT and both TH and GAP43-positive nerve fiber density in the infarct border zone (P < 0.05). Desipramine treatment before acute myocardial ischemia can decrease infarct size, improve sympathetic remodeling, and increase VFT and electrical stability of ischemic hearts. Desipramine appears to cause myocardial ischemic preconditioning.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Province, Wuhan 430060, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Lilei
authors.initials: L
authors.lastname: Yu
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Hu
authors.forename: Wenwei
authors.initials: W
authors.lastname: Liu
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage; D000818:Animals; D003891:Desipramine / Q000008:administration & dosage*; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D011292:Premedication / Q000379:methods*; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D003891:Desipramine