title: Ephedrine plus caffeine causes age-dependent cardiovascular responses in Fischer 344 rats.
abstract: Human consumption of ephedrine and caffeine in dietary supplements has been associated with a number of adverse effects including changes in the ECG, myocardial infarction, hyperthermia, and, in rare instances, death. The purpose of this study was to investigate the potential mechanisms associated with the cardiotoxicity of combined ephedrine and caffeine ingestion. Seven- and fourteen-week-old Fischer 344 rats treated with ephedrine in combination with caffeine exhibited increases in heart rate (HR), temperature, and corrected QT interval. Of the 14-wk-old rats treated with 25 mg/kg ephedrine plus 30 mg/kg caffeine, 57% died within 3-5 h of treatment, whereas none of the similarly treated 7-wk-old rats nor any of the rats treated with vehicle died. One hour after treatment with this dose of ephedrine plus caffeine, 14-wk-old rats exhibited a larger increase in HR (as % increase over baseline) than 7-wk-old rats. Furthermore, the 14-wk-old rats that died had a higher HR and temperature than the 14-wk-old rats that lived. Histopathological studies suggested interstitial hemorrhage and myofiber necrosis in the 14-wk-old rats treated with the highest concentration of ephedrine and caffeine. This study showed enhanced susceptibility to ephedrine plus caffeine in 14-wk-old rats compared with 7-wk-old rats. The greater mortality in the 14-wk-old rats was associated with increases in body temperature, HR, and myocardial necrosis.
authors.affiliation: Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Reuben
authors.initials: R
authors.lastname: Howden
authors.forename: Paul R
authors.initials: PR
authors.lastname: Hanlon
authors.forename: John G
authors.initials: JG
authors.lastname: Petranka
authors.forename: Steven
authors.initials: S
authors.lastname: Kleeberger
authors.forename: John
authors.initials: J
authors.lastname: Bucher
authors.forename: June
authors.initials: J
authors.lastname: Dunnick
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Murphy
mesh_terms: D000367:Age Factors; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002110:Caffeine / Q000633:toxicity*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004357:Drug Synergism; D004562:Electrocardiography / Q000187:drug effects; D004809:Ephedrine / Q000633:toxicity*; D005334:Fever / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine; D004809:Ephedrine