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Published on: July 29, 2011
Adenine nucleotides and ventricular fibrillation
W F Lubbe1, A I Gilchrist, R K Holland
1Department of Medicine, University of Auckland, New Zealand.
Journal of Molecular and Cellular Cardiology
|October 1, 1987
Summary
Cyclic AMP increases ventricular fibrillation risk during early ischemia. Adenosine and its analogues act as antagonists, reducing this risk and offering potential antiarrhythmic benefits in myocardial ischemia.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Pharmacology
Background:
- Ventricular fibrillation (VF) is a major cause of sudden cardiac death.
- Early myocardial ischemia significantly increases vulnerability to VF.
- The role of adenine nucleotides and cyclic AMP in VF genesis requires further elucidation.
Purpose of the Study:
- To investigate the influence of adenine nucleotides and their metabolites on myocardial vulnerability to VF.
- To determine the relationship between tissue cyclic AMP levels and VF incidence.
- To evaluate the antiarrhythmic potential of adenosine and its analogues.
Main Methods:
- Isolated perfused rat heart model subjected to coronary artery ligation.
- Manipulation of extracellular K+ concentration to induce arrhythmias.
- Assay of myocardial adenine nucleotides, cyclic AMP, lactate, and high-energy phosphates.
- Administration of dibutyryl cyclic AMP (dbcAMP) and adenosine analogues.
Main Results:
- VF incidence correlated directly with tissue cyclic AMP levels, not lactate or high-energy phosphates.
- DbcAMP administration reduced the VF threshold, an effect antagonized by adenosine and N-ethylcarboxamidoadenosine.
- Adenosine analogues demonstrated antiarrhythmic activity and antagonized dbcAMP-induced QT prolongation.
Conclusions:
- Elevated cyclic AMP contributes to increased vulnerability to VF during early myocardial ischemia.
- Adenosine and specific analogues possess antiarrhythmic properties by antagonizing cyclic AMP-mediated effects.
- Adenosine may serve as a protective agent against VF in acute ischemic events.
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