Thromboxane A2-induced arrhythmias in the anesthetized rabbit

Michael J. Wacker, Shaun R. Best, Lisa M. Kosloski, Christopher J. Stachura, Rory L. Smoot, Charles B. Porter, James A. Orr

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Experiments were conducted in the anesthetized rabbit to investigate mechanisms for arrhythmias that occur after left atrial injection of the thromboxane A2 (TxA2) mimetic U-46619. Arrhythmias were primarily of ventricular origin, dose dependent in frequency, and TxA 2 receptor mediated. The response was receptor specific since arrhythmias were absent after pretreatment with a specific TxA2 receptor antagonist (SQ-29548) and did not occur in response to another prostaglandin, PGF. Alterations in coronary blood flow were unlikely the cause of these arrhythmias because coronary blood flow (as measured with florescent microspheres) was unchanged after U-46619, and there were no observable changes in the ECG-ST segment. In addition, arrhythmias did not occur after administration of another vasoconstrictor (phenylephrine). The potential involvement of autonomic cardiac efferent nerves in these arrhythmias was also investigated because TxA2 has been shown to stimulate peripheral nerves. Pretreatment of animals with the β-adrenergic receptor antagonist propranolol did not reduce the frequency of these arrhythmias. Pretreatment with atropine or bilateral vagotomy resulted in an increased frequency of arrhythmias, suggesting that parasympathetic nerves may actually inhibit the arrhythmogenic activity of TxA2. These experiments demonstrate that left atrial injection of U-46619 elicits arrhythmias via a mechanism independent of a significant reduction in coronary blood flow or activation of the autonomic nervous system. It is possible that TxA2 may have a direct effect on the electrical activity of the heart in vivo, which provides significant implications for cardiac events where TxA2 is increased, e.g., after myocardial ischemia or administration of cyclooxygenase-2 inhibitors.

Original languageEnglish (US)
Pages (from-to)H1353-H1361
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume290
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • Autonomic nervous system
  • Coronary blood flow
  • Phenylephrine
  • Prostaglandin F
  • SQ-29548
  • U-46619

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Wacker, M. J., Best, S. R., Kosloski, L. M., Stachura, C. J., Smoot, R. L., Porter, C. B., & Orr, J. A. (2006). Thromboxane A2-induced arrhythmias in the anesthetized rabbit. American Journal of Physiology - Heart and Circulatory Physiology, 290(4), H1353-H1361. https://doi.org/10.1152/ajpheart.00930.2005