Influence of zoledronic acid on atrial electrophysiological parameters and electrocardiographic measurements

James E. Tisdale, Matthew Allen, Brian R. Overholser, Heather A. Jaynes, Richard Kovacs

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 (APD<inf>90</inf>) decreased more from baseline than in controls (-23.2% ± -5.1% vs. -2.1% ± -8.1%, P < 0.0001), as did APD<inf>30</inf> (-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 APD<inf>30</inf> 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.

Original languageEnglish
Pages (from-to)671-677
Number of pages7
JournalJournal of Cardiovascular Electrophysiology
Volume26
Issue number6
DOIs
StatePublished - Jun 1 2015

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zoledronic acid
pamidronate
Placebos
Electrophysiology

Keywords

  • action potential
  • atrial fibrillation
  • bisphosphonates
  • electrocardiography
  • P wave
  • PR interval
  • proarrhythmia
  • zoledronic acid

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Influence of zoledronic acid on atrial electrophysiological parameters and electrocardiographic measurements. / Tisdale, James E.; Allen, Matthew; Overholser, Brian R.; Jaynes, Heather A.; Kovacs, Richard.

In: Journal of Cardiovascular Electrophysiology, Vol. 26, No. 6, 01.06.2015, p. 671-677.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Jaynes, Heather A.

AU - Kovacs, Richard

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N2 - 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.

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KW - atrial fibrillation

KW - bisphosphonates

KW - electrocardiography

KW - P wave

KW - PR interval

KW - proarrhythmia

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