{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:08:26Z","timestamp":1777914506061,"version":"3.51.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[1994,1,1]],"date-time":"1994-01-01T00:00:00Z","timestamp":757382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[1994,1]]},"abstract":"<jats:p>Asthma morbidity and mortality have risen significantly in the last 10 years. The reasons for the increase are multifactorial. One proposed explanation is possible myocardial toxicity arising from the use of \u03b2-agonists alone or in combination with methylxanthines. Previous studies have shown that \u03b2-agonists given alone and \u03b2-agonist\/methylxanthine combinations given at higher than recommended clinical doses induced dose-related cardiotoxicity and sudden death in rats. The objective of the present study was to determine whether or not \u03b2-agonists given alone and in combination with methylxanthines at recommended clinical doses also induce cardiotoxicity and sudden death in rats. The \u03b2-agonists, isoproterenol hydrochloride (15 \u03bcg\/kg), fenoterol hydrobromide (40 \u03bcg\/kg), and terbutaline hemisulfate (0.4 mg\/kg) were given in single sc doses separately and concurrently with the methylxanthines aminophylline hydrate (20 mg\/kg) and caffeine (40 mg\/kg), which were given ip to a susceptible animal model, the heavy Sprague-Dawley rat. \u03b2-agonist-induced myocardial toxicity (necrosis) was observed. The toxicity was enhanced by aminophylline resulting in the sudden death (most likely due to ventricular fibrillation) of some animals. A decrease in serum iron levels was observed in rats of all \u03b2-agonist and\/or methylxanthine-treated groups.<\/jats:p>","DOI":"10.1177\/019262339402200110","type":"journal-article","created":{"date-parts":[[2009,9,14]],"date-time":"2009-09-14T21:30:11Z","timestamp":1252963811000},"page":"72-76","source":"Crossref","is-referenced-by-count":10,"title":["Enhancement of Acute Myocardial Lesions by Asthma Drugs in Rats"],"prefix":"10.1177","volume":"22","author":[{"given":"Virgil E.","family":"Whitehurst","sequence":"first","affiliation":[{"name":"Center for Drug Evaluation and Research"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Joseph","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederic R.","family":"Alleva","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A.","family":"Vick","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Whittaker","sequence":"additional","affiliation":[{"name":"Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, D.C. 20204"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Bert E.","family":"Fry","sequence":"additional","affiliation":[{"name":"Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, D.C. 20204"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tibor","family":"Balazs","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[1994,1,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-71248-7_22"},{"key":"atypb2","first-page":"1170","volume":"60","author":"Boline DR","year":"1977","journal-title":"J. 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