Document Detail

Importance of extracardiac alpha1-adrenoceptor stimulation in assisting dofetilide to induce torsade de pointes in rabbit hearts.
MedLine Citation:
PMID:  16618484     Owner:  NLM     Status:  MEDLINE    
In anaesthetized rabbits, alpha(1)-adrenoceptor stimulation increases the propensity of repolarization-prolonging drugs to induce torsade de pointes ventricular tachycardia. However, it is not known whether the stimulation of intracardiac alpha(1)-adrenoceptors, or the increased ventricular stretch caused by extracardiac alpha(1)-adrenoceptor-mediated peripheral vasoconstriction and increased resistance, are the sensitizing factors. Accordingly, this study investigated whether a sustained load-induced left ventricular stretch or stimulation of the intracardiac alpha(1)-adrenoceptors with 100 nM methoxamine, or the co-application of these two, can assist dofetilide (100 nM) to elicit torsade de pointes in isolated Langendorff-perfused, rabbit hearts. In the stretched hearts, a constant high level of stretch was produced by a water-filled left ventricular balloon inflated to a volume of 1.4 ml, whereby the systolic and end-diastolic pressures virtually did not exceed the physiological range (<or=157+/-11 mm Hg and <or=9+/-2 mm Hg, respectively; mean+/-S.E.M.). Perfusion with dofetilide prolonged the QT interval significantly and indifferently in all hearts. Neither this stretch nor methoxamine nor the in combination affected the QT interval, the heart rate or the coronary flow. Interestingly, neither the stretch ('dofetilide+stretch' group, n=8 hearts), nor methoxamine ('dofetilide+methoxamine' group, n=8 hearts), nor the in combination ('dofetilide+stretch+methoxamine' group, n=8 hearts) elevated the incidence of torsade de pointes as compared with the 'dofetilide alone' group (n=9 hearts) (0%, 25%, 0%, versus 44%, respectively). In conclusion, neither a sustained load-induced stretch nor alpha(1)-adrenoceptor stimulation nor the in combination assisted dofetilide to induce torsade de pointes in isolated rabbit hearts, suggesting the importance of extracardiac alpha(1)-adrenoceptor stimulation in this phenomenon.
Attila S Farkas; Károly Acsai; András Tóth; László Dézsi; Szabolcs Orosz; Tamás Forster; Miklós Csanády; Julius Gy Papp; András Varró; András Farkas
Related Documents :
23018394 - Using the braden scale and photographs to assess pressure ulcer risk.
25064794 - Spinal cord injury pressure ulcer treatment: an experience-based approach.
8759074 - Negative chronotropic effect of beta-blockade therapy reduces myocardial oxygen expendi...
9540134 - Betablockers: old concept in a modern approach.
11468204 - Sildenafil inhibits hypoxia-induced pulmonary hypertension.
11998994 - Determinants of fi,o2 with oxygen supplementation during noninvasive two-level positive...
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-20
Journal Detail:
Title:  European journal of pharmacology     Volume:  537     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-08     Completed Date:  2006-08-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  118-25     Citation Subset:  IM    
2nd Department of Internal Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Korányi fasor 6., Szeged, H-6701, Hungary.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adrenergic alpha-Agonists / pharmacology
Anti-Arrhythmia Agents / pharmacology*
Heart Rate / drug effects
Heart Ventricles / drug effects*,  physiopathology
Methoxamine / pharmacology
Phenethylamines / pharmacology*
Receptors, Adrenergic, alpha-1 / agonists*,  physiology
Regional Blood Flow / drug effects
Sulfonamides / pharmacology*
Torsades de Pointes / chemically induced,  physiopathology*
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 0/Anti-Arrhythmia Agents; 0/Phenethylamines; 0/Receptors, Adrenergic, alpha-1; 0/Sulfonamides; 115256-11-6/dofetilide; 390-28-3/Methoxamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Estimating the effect of air pollution from a coal-fired power station on the development of childre...
Next Document:  The relevance of psychosocial variables and working conditions in predicting nurses' coping strategi...