Basic Research in Cardiology

, Volume 77, Issue 4, pp 411–422 | Cite as

Lack of thromboxane A2 involvement in the arrhythmias occurring during acute myocardial ischemia in dogs

  • S. E. Burke
  • M. J. Antonaccio
  • A. M. Lefer
Original Contributions


Coronary artery occlusion (CAO) followed by reperfusion of the ischemic myocardium has been associated with the onset of ventricular arrhythmias. It has been suggested that platelet aggregates in the ischemic area may release thromboxane A2 (TxA2) which may then be responsible for the arrhythmias that occur during reperfusion. To study this possibility, the effect of TxA2 synthetase inhibition on arrhythmias was examined in anesthetized dogs during occlusion and for 60 minutes following release. Imidazole (30 mg/kg) was infused intravenously for 10 minutes, followed by continuous infusion of 100 mg/kg/hr for 125 minutes. The left anterior descending coronary artery was occluded, 5 minutes after the initial dose, for 60 minutes. Three minutes after release of CAO, TxB2 concentrations were significantly higher in the arterial blood of vehicle-treated animals (2.06±0.53 pmoles/ml) than in either CAO + imidazole (0.66±0.16 pmoles/ml) or sham-CAO animals receiving imidazole (0.66±0.09 pmoles/ml). However, CAO dogs whether receiving imidazole or 0.9% NaCl generated a significantly greater number of ectopic beats during and after occlusion than sham-CAO animals. Therefore, release of TxA2 does not appear to be a major causative factor in the generation of reperfusion arrhythmias in dogs following coronary artery occlusion.

Key words

thromboxane B2 coronary artery occlusion imidazole reperfusion arrhythmias coronary blood flow 


Koronarokklusion mit nachfolgender Reperfusion des ischämischen Myokards löst ventrikuläre Rhythmusstörungen aus. Es wurde vermutet, daß Plättchenaggregate im ischämischen Bereich Thromboxan A2 freigeben und daß diese Substanz für die während der Reperfusionsphase auftretenden Arrhythmien verantwortlich sein könnte. Um diese Möglichkeit zu untersuchen, wurde der Effekt einer Hemmung der Thromboxan-A2-Synthetase bei narkotisierten Hunden während der Arterienabklemmung und über 60 Minuten nach Öffnung des Verschlusses geprüft. Imidazol (30 mg/kg) wurde über 10 Minuten intravenös infundiert, gefolgt von einer kontinuierlichen Infusion von 100 mg/kg/h über einen Zeitraum von 125 Minuten. Der Ram. descendens der linken Koronararterie wurde, beginnend 5 Minuten nach der initialen Dosis, für 60 Minuten verschlossen. 3 Minuten nach Öffnung des Arterienverschlusses waren die Thromboxan-B2-Konzentrationen im Blut derjenigen Tiere, denen nur Lösungsmittel injiziert wurde, signifikant höher (2,06±0,35 pmoles/ml) als bei Tieren mit Okklusion+Imidazol (0,60±0,16 pmoles/ml) oder scheinoperierten Tieren, welche Imidazol erhielten (0,66±0,09 pmoles/ml). Jedoch traten bei den Hunden mit Okklusion, gleichgültig ob sie Imidazol oder 0,9%ige Kochsalzlösung erhielten, eine signifikant größere Zahl von ektopischen Schlägen während und nach der Okklusion auf als bei scheinoperierten Tieren. Somit scheint die Freisetzung von Thromboxan A2 kein wesentlicher Faktor bei der Entstehung von Arrhythmien in der Reperfusionsphase nach Koronararterienokklusion des Hundes zu sein.


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Copyright information

© Dr. Dietrich Steinkopff Verlag 1982

Authors and Affiliations

  • S. E. Burke
    • 1
    • 2
  • M. J. Antonaccio
    • 1
    • 2
  • A. M. Lefer
    • 1
    • 2
  1. 1.Department of PharmacologySquibb Institute for Medical ResearchPrinceton
  2. 2.Department of Physiology, Jefferson Medical CollegeThomas Jefferson UniversityPhiladelphiaUSA

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