Tisdale, James E.Allen, Matthew R.Overholser, Brian R.Jaynes, Heather A.Kovacs, Richard J.2017-02-222017-02-222015-06Tisdale, J. E., Allen, M. R., Overholser, B. R., Jaynes, H. A., & Kovacs, R. J. (2015). Influence of Zoledronic Acid on Atrial Electrophysiological Parameters and Electrocardiographic Measurements. Journal of Cardiovascular Electrophysiology, 26(6), 671–677. http://doi.org/10.1111/jce.126411540-8167https://hdl.handle.net/1805/11960INTRODUCTION: 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.en-USPublisher PolicyAction Potentialsdrug effectsBone Density Conservation AgentspharmacologyDiphosphonatesElectrocardiographyImidazolesArticle