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Published on: May 26, 2010
Pronounced antiarrhythmic effects of preconditioning in anaesthetized dogs: is adenosine involved?
A Vegh1, J G Papp, J R Parratt
1Department of Pharmacology, Albert Szent-Gyorgyi Medical University, Szeged, Hungary.
Insights
Adenosine does not appear to mediate the antiarrhythmic effects of ischemic preconditioning, despite its role in reducing infarct size. Blocking adenosine receptors did not abolish the protective antiarrhythmic benefits of preconditioning.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Adenosine is known to mediate myocardial protection against ischemic damage.
- The role of adenosine in the antiarrhythmic effects of ischemic preconditioning is not well-established.
Purpose of the Study:
- To investigate whether adenosine contributes to the antiarrhythmic effects of ischemic preconditioning in a canine model.
Main Methods:
- Anesthetized dogs underwent coronary artery occlusions to induce preconditioning.
- The non-selective adenosine receptor antagonist 8-sulfophenyltheophylline (8-SPT) was administered.
- Ventricular arrhythmias were monitored during preconditioning and prolonged ischemia.
Main Results:
- 8-SPT administration reduced coronary blood flow and increased cardiovascular resistance.
- Preconditioning was more difficult in the presence of 8-SPT, with increased ventricular premature beats and fibrillation during the initial occlusion.
- Despite this, preconditioning was still possible, and no ventricular fibrillation occurred during the prolonged occlusion in treated dogs.
- The incidence of ventricular tachycardia and premature beats was similar to dogs preconditioned without 8-SPT and significantly lower than controls.
Conclusions:
- Adenosine does not appear to mediate the antiarrhythmic effects of ischemic preconditioning.
- Ischemic preconditioning confers significant protection against ventricular arrhythmias, independent of adenosine receptor activity.
Abstract:
Although there is good evidence that adenosine contributes to the ability of ischaemic preconditioning to reduce myocardial ischaemic damage (infarct size) there is no evidence that it contributes to the marked antiarrhythmic effects of this endogenous protective mechanism. We have examined this in anaesthetized open-chest mongrel dogs by administering the non-selective adenosine receptor blocking drug 8-sulfophenyltheophylline (8-SPT) (1 mg/kg) given by intracoronary administration 10 min before both 5 min preconditioning coronary artery occlusions and also before the prolonged 25 min LAD occlusion i.e. in a total dose of 3 mg/kg. The only haemodynamic effect of 8-SPT was a reduction in coronary (LAD) blood flow and an increase in cardiovascular resistance. It was difficult to precondition dogs in the presence of 8-SPT; the number of ventricular premature beats was significantly higher (61 +/- 6 v 8 +/- 4; P < 0.01) during the initial preconditioning occlusion and the incidence of ventricular fibrillation during the preconditioning procedure was higher in the presence of the drug (5/11 v 4/20; P < 0.05). Nevertheless, it was still possible to precondition these dogs in the presence of the drug. No VF occurred during the prolonged occlusion (cf. 50% in the controls) and the number of episodes of ventricular tachycardia, and the number of ventricular premature beats in dogs preconditioned in the presence of 8-SPT was similar to those in dogs preconditioned without 8-SPT and significantly (P < 0.01 or P < 0.05) less than in control, non-preconditioned dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
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