title: Acute clenbuterol induces hypotension, atrioventricular block and cardiac asystole in the rabbit.
abstract: Clenbuterol is a long-lasting β-adrenoceptor (β-AR) agonist and was once medicated as a bronchial dilatator, and is also used by body-building enthusiasts and athletes and in livestock breeding because of its anabolic effect on skeletal muscles and ability to promote lipolysis. Though prohibited from pharmacological uses, clenbuterol intoxication cases are frequently reported, and most of the cardiac symptoms are tachyarrhythmia. Here, we reported a different cardiovascular toxic response to clenbuterol. Using a rabbit model, we tested the dose-response pattern of the cardiovascular system to intravenous administration of clenbuterol. Routine arterial blood pressure (BP) and surface electrocardiogram (ECG) were monitored. We observed that clenbuterol at a lower dose (0.4 mg/kg, n = 3) did not significantly affect the ECG, but decreased the mean BP roughly by 15-18 mmHg. At a medial dose (3.6 mg/kg, n = 3), clenbuterol induced significant hypotension (mean BP dropped by about 30 mmHg), first-degree atrioventricular (AV) block and intermittent ectopic activities with a relatively slow rate. The hypotension and arrhythmia recovered slowly, and animals did not die. Higher-dose clenbuterol (10 mg/kg, n = 6) induced severe hypotension, second-degree AV block (Mobitz type II), 2:1 ventricular capture and progressive prolongations of P-R intervals and QRS duration, and the animals soon died of cardiac asystole. Different from other reports, we had not observed lethal tachyarrhythmia in all experiments except for the slight heart rate acceleration during the recovery stage of medial clenbuterol dosage. These results indicate that acute intravenous administration of clenbuterol has serious, dose-dependent cardiovascular toxicities and is even life threatening.
authors.affiliation: Department of Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ke
authors.forename: Li-Lan
authors.initials: LL
authors.lastname: Fu
authors.forename: Xia-Fei
authors.initials: XF
authors.lastname: Hong
authors.forename: Run
authors.initials: R
authors.lastname: Dong
authors.forename: Tian-Ming
authors.initials: TM
authors.lastname: Xu
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Cao
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D054537:Atrioventricular Block / Q000139:chemically induced* / Q000503:physiopathology; D002976:Clenbuterol / Q000008:administration & dosage / Q000633:toxicity*; D006323:Heart Arrest / Q000139:chemically induced* / Q000503:physiopathology; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D011817:Rabbits
chemical_list: D000318:Adrenergic beta-Agonists; D002976:Clenbuterol