title: Propranolol pretreatment reduces cardiorespiratory toxicity due to plain, but not epinephrine-containing, intravenous bupivacaine in rats.
abstract: The purpose of this study was to evaluate the effects of pretreatment with propranolol on the cardio-respiratory toxicity of bupivacaine, either plain or with epinephrine 1:200,000 (5 micrograms.ml-1) added. Adult male Sprague Dawley rats, anaesthetized with intraperitoneal pentobarbital, were divided into four groups. Groups I and III were pretreated with iv propranolol 150 micrograms.kg-1, and Groups II and IV received iv NS as a placebo. Three minutes later, rats in Groups I and II received plain 0.5% bupivacaine, 4 mg.kg-1, and Groups III and IV received 4 mg.kg-1 of 0.5% bupivacaine with epinephrine, 5 micrograms.ml-1 iv. Five of eight rats pretreated with propranolol survived (Group I), compared with uniform fatality with NS pretreatment (Group II) (P less than 0.05). Addition of epinephrine to the bupivacaine eliminated the protective effect of propranolol. All rats pretreated with propranolol (Group III) or NS (Group IV) died when given bupivacaine with epinephrine. In conclusion, acute propranolol pretreatment reduced the fatal cardiotoxicity due to iv bupivacaine in male Sprague Dawley rats, but the addition of epinephrine 5 micrograms.ml-1 to bupivacaine eliminated the protective effect of propranolol.
authors.affiliation: Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232-2125.
authors.forename: W W
authors.initials: WW
authors.lastname: Kinney
authors.forename: J R
authors.initials: JR
authors.lastname: Kambam
authors.forename: W
authors.initials: W
authors.lastname: Wright
mesh_terms: D000818:Animals; D001049:Apnea / Q000139:chemically induced; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects*; D008297:Male; D011229:Preanesthetic Medication; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D011433:Propranolol; D002045:Bupivacaine; D004837:Epinephrine