title: Bupivacaine inhibits baroreflex control of heart rate in conscious rats.
abstract: BACKGROUND
  Because exposure to intravenously administered bupivacaine may alter cardiovascular reflexes, the authors examined bupivacaine actions on baroreflex control of heart rate in conscious rats.
  
  
  METHODS
  Baroreflex sensitivity (pulse interval vs. systolic blood pressure in ms/mmHg) was determined before, and 1.5 and 15.0 min after rapid intravenous administration of bupivacaine (0.5, 1.0, and 2.0 mg/kg) using heart rate changes evoked by intravenously administered phenylephrine or nitroprusside. The actions on the sympathetic and parasympathetic autonomic divisions of the baroreflex were tested in the presence of a muscarinic antagonist methyl atropine and a beta-adrenergic antagonist atenolol.
  
  
  RESULTS
  Within seconds of injection of bupivacaine, mean arterial pressure increased and heart rate decreased in a dose-dependent manner. Baroreflex sensitivity was unaltered after administration of 0.5 mg/kg bupivacaine. In addition, 1 mg/kg bupivacaine at 1.5 min depressed phenylephrine-evoked reflex bradycardia (0.776 +/- 0.325 vs. 0.543 +/- 0.282 ms/mmHg, P < 0.05) but had no effect on nitroprusside-induced tachycardia. Bupivacaine (2 mg/kg), however, depressed reflex bradycardia and tachycardia (phenylephrine, 0.751 +/- 0.318 vs. 0.451 +/- 0.265; nitroprusside, 0.839 +/- 0.256 vs. 0.564 +/- 0.19 ms/mmHg, P < 0.05). Baroreflex sensitivity returned to prebupivacaine levels by 15 min. Bupivacaine (2 mg/kg), in the presence of atenolol, depressed baroreflex sensitivity (phenylephrine, 0.633 +/- 0.204 vs. 0.277 +/- 0.282; nitroprusside, 0.653 +/- 0.142 vs. 0.320 +/- 0.299 ms/mmHg, P < 0.05). In contrast, bupivacaine did not alter baroreflex sensitivity in the presence of methyl atropine.
  
  
  CONCLUSIONS
  Bupivacaine, in clinically relevant concentrations, inhibits baroreflex control of heart rate in conscious rats. This inhibition appears to involve primarily vagal components of the baroreflex-heart rate pathways.
authors.affiliation: Department of Anesthesiology, Oregon Health Sciences University and Veterans Affairs Medical Center, Portland 97201, USA. ChangK@ohsu.edu
authors.forename: K S
authors.initials: KS
authors.lastname: Chang
authors.forename: D R
authors.initials: DR
authors.lastname: Morrow
authors.forename: K
authors.initials: K
authors.lastname: Kuzume
authors.forename: M C
authors.initials: MC
authors.lastname: Andresen
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000779:Anesthetics, Local; D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D009599:Nitroprusside; D010656:Phenylephrine; D001262:Atenolol; D002045:Bupivacaine