Influence of Zoledronic Acid on Atrial Electrophysiological Parameters and Electrocardiographic Measurements

• Published in: Journal of cardiovascular electrophysiology Vol. 26; no. 6; pp. 671 - 677
• Main Authors: TISDALE, JAMES E., ALLEN, MATTHEW R., OVERHOLSER, BRIAN R., JAYNES, HEATHER A., KOVACS, RICHARD J.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.06.2015; Wiley Subscription Services, Inc
• Subjects: action potential; Action Potentials - drug effects; Animals; atrial fibrillation; Atrial Fibrillation - epidemiology; bisphosphonates; Bone Density Conservation Agents - pharmacology; Diphosphonates - pharmacology; Dogs; Dose-Response Relationship, Drug; electrocardiography; Electrocardiography - drug effects; Female; Guinea Pigs; Imidazoles - pharmacology; P wave; Perfusion - methods; PR interval; proarrhythmia; Risk; zoledronic acid; atrial fibrillation; zoledronic acid; P wave; PR interval; bisphosphonates; action potential; proarrhythmia; electrocardiography
• ISSN: 1045-3873; 1540-8167
• DOI: 10.1111/jce.12641

Zoledronic Acid Alters Atrial Electrophysiology Introduction Our objective was to determine effects of zoledronic acid (ZA) on atrial electrophysiological parameters and electrocardiographic measurements. Methods and 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. Conclusion ZA shortens left atrial APD and ERP and increases P wave dispersion.