NTRODUCTION:
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 two weeks in one 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 two 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
Action potential; P wave; PR interval; atrial fibrillation; bisphosphonates; electrocardiography; proarrhythmia; zoledronic acid
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