James E Tisdale1,2, Matthew R Allen3, Brian R Overholser1,2, Heather A Jaynes1, Richard J Kovacs4. 1. Department of Pharmacy Practice, College of Pharmacy, Purdue University, Indianapolis, Indiana, USA. 2. Division of Clinical Pharmacology, Department of Medicine, Indianapolis, Indiana, USA. 3. Department of Anatomy and Cell Biology, Indianapolis, Indiana, USA. 4. Krannert Institute of Cardiology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Abstract
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.
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.
Authors: Dennis M Black; Pierre D Delmas; Richard Eastell; Ian R Reid; Steven Boonen; Jane A Cauley; Felicia Cosman; Péter Lakatos; Ping Chung Leung; Zulema Man; Carlos Mautalen; Peter Mesenbrink; Huilin Hu; John Caminis; Karen Tong; Theresa Rosario-Jansen; Joel Krasnow; Trisha F Hue; Deborah Sellmeyer; Erik Fink Eriksen; Steven R Cummings Journal: N Engl J Med Date: 2007-05-03 Impact factor: 91.245
Authors: Penelope D Ottewell; Hannu Mönkkönen; Mark Jones; Diane V Lefley; Robert E Coleman; Ingunn Holen Journal: J Natl Cancer Inst Date: 2008-08-11 Impact factor: 13.506
Authors: I Aktas; C Nazikoglu; A Kepez; F U Ozkan; M Y Kaysin; P Akpinar; Z Dogan; C Ileri; S Saymaz; O Erdogan Journal: Osteoporos Int Date: 2016-06-25 Impact factor: 4.507