HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/4/H1353    most recent 00930.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wacker, M. J. Articles by Orr, J. A. Search for Related Content PubMed PubMed Citation Articles by Wacker, M. J. Articles by Orr, J. A.

CALL FOR PAPERS
Regulation of Cardiovascular Functions by Eicosanoids and Other Lipid Mediators

Thromboxane A₂-induced arrhythmias in the anesthetized rabbit

¹Department of Molecular Biosciences, University of Kansas, Lawrence; and ²Department of Medicine, University of Kansas Medical Center, Kansas City, Kansas

Submitted 30 August 2005 ; accepted in final form 7 December 2005

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 TxA₂ 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, PGF₂. 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 -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.

autonomic nervous system; coronary blood flow; prostaglandin F₂; phenylephrine; SQ-29548; U-46619