title: Influence of Zoledronic Acid on Atrial Electrophysiological Parameters and Electrocardiographic Measurements.
abstract: BACKGROUND
  Our objective was to determine effects of zoledronic acid (ZA) on atrial electrophysiological parameters and electrocardiographic measurements.
  
  
  RESULTS
  Ex vivo perfusion study: Isolated guinea pig hearts were perfused with modified Krebs-Henseleit (K-H) buffer with or without ZA 0.07 mg/kg/L (each n = 6). In ZA-perfused hearts, atrial action potential at 90% repolarization (APD90 ) decreased more from baseline than in controls (-23.2% ± -5.1% vs. -2.1% ± -8.1%, P < 0 .0001), as did APD30 (-28.8% ± -3.8% vs. -2.1% ± -2.1%, P < 0.0001). In vivo dose-response study: Guinea pigs underwent intraperitoneal injections every 2 weeks in 1 of 4 groups (each n = 8): ZA 0.007 mg/kg (low-dose), ZA 0.07 mg/kg (medium-dose), ZA 0.7 mg/kg (high-dose), or placebo. Hearts were excised at 8 weeks and perfused with modified K-H. Atrial effective refractory period (ERP) was lower with medium- and high-dose ZA versus placebo (P = 0.004). Atrial APD30 was lower with high-dose ZA versus placebo, low and medium doses (P < 0.001). Canine ECG study: Mature female beagles received intravenous ZA 0.067 mg/kg or saline (placebo; each n = 6) every 2 weeks for 12 weeks. P wave dispersion was greater in the ZA group (7.7 ± 3.7 vs. 3.4 ± 2.6 ms, P = 0.04). There were no significant differences in P wave index, maximum or minimum P wave duration, or PR interval.
  
  
  CONCLUSIONS
  ZA shortens left atrial APD and ERP and increases P wave dispersion.
authors: Department of Pharmacy Practice, College of Pharmacy, Purdue University, Indianapolis, Indiana, USA.|Division of Clinical Pharmacology, Department of Medicine, Indianapolis, Indiana, USA.
authors: James E
authors: JE
authors: Tisdale
authors: Department of Anatomy and Cell Biology, Indianapolis, Indiana, USA.
authors: Matthew R
authors: MR
authors: Allen
authors: Department of Pharmacy Practice, College of Pharmacy, Purdue University, Indianapolis, Indiana, USA.|Division of Clinical Pharmacology, Department of Medicine, Indianapolis, Indiana, USA.
authors: Brian R
authors: BR
authors: Overholser
authors: Department of Pharmacy Practice, College of Pharmacy, Purdue University, Indianapolis, Indiana, USA.
authors: Heather A
authors: HA
authors: Jaynes
authors: Krannert Institute of Cardiology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
authors: Richard J
authors: RJ
authors: Kovacs
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001281:Atrial Fibrillation / Q000453:epidemiology; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods; D012306:Risk; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: P wave; PR interval; action potential; atrial fibrillation; bisphosphonates; electrocardiography; proarrhythmia; zoledronic acid