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Reduction of myocardial infarct size by dronedarone in pigs--a pleiotropic action?
Andreas Skyschally1, Gerd Heusch
1Institut für Pathophysiologie, Universitätsklinikum Essen, Hufelandstr. 55, 45122, Essen, Germany.
Insights
Dronedarone significantly reduced heart attack size in pigs by protecting against ischemia/reperfusion injury. This suggests potential cardioprotective benefits beyond its use in atrial fibrillation.
Area of Science:
- Cardiology
- Pharmacology
- Cardiovascular Research
Background:
- Dronedarone is a first-line antiarrhythmic drug for atrial fibrillation (AF) per ESC guidelines.
- The ATHENA trial showed dronedarone reduces mortality and acute coronary syndrome hospitalizations in AF patients.
- These findings suggest potential benefits in ischemia/reperfusion injury.
Purpose of the Study:
- To investigate the cardioprotective effects of dronedarone during myocardial ischemia/reperfusion.
- To determine if dronedarone impacts infarct size independently of its effects on heart rate and blood pressure.
Main Methods:
- Anesthetized pigs underwent 90 minutes of regional low-flow myocardial ischemia followed by 2 hours of reperfusion.
- Dronedarone (2.5 mg/kg) or placebo was administered; hemodynamic effects were controlled.
- Regional myocardial blood flow was measured using microspheres, and infarct size was assessed by TTC staining.
Main Results:
- Dronedarone significantly reduced infarct size (34% to 22% of the area at risk, p < 0.05) compared to placebo.
- No significant difference in subendocardial blood flow during ischemia was observed between groups.
- A downward shift in the relationship between ischemic blood flow and infarct size indicated direct cardioprotection.
Conclusions:
- Dronedarone exhibits direct cardioprotective properties against myocardial ischemia/reperfusion injury.
- These effects may be mediated by the attenuation of calcium overload during the ischemic-reperfusion process.
- Findings suggest a potential therapeutic role for dronedarone in managing ischemic heart conditions.
Purpose:
Dronedarone is a first-line drug to prevent the recurrence of atrial fibrillation according to ESC guidelines. In the recent ATHENA trial, dronedarone reduced mortality and also hospitalization for acute coronary syndrome in patients with atrial fibrillation. This beneficial effect suggests that dronedarone might have also an impact on events associated with ischemia/reperfusion injury.
Methods:
Fourteen anesthetized pigs received either dronedarone (2.5 mg/kg) or placebo. Effects of dronedarone on heart rate and blood pressure were reversed by atrial pacing and aortic constriction before pigs were subjected to 90 min regional low-flow myocardial ischemia and 2 h reperfusion. Regional myocardial blood flow was measured with microspheres and infarct size determined by TTC staining.
Results:
With comparable heart rate and left ventricular pressure during ischemia, dronedarone reduced infarct size from 34 ± 3% to 22 ± 4% (p < 0.05) of the area at risk. Subendocardial blood flow during ischemia was not different between groups. The relationship between ischemic subendocardial blood flow in the area at risk and infarct size was displaced downwards, reflecting a direct cardioprotective action of dronedarone.
Conclusion:
The beneficial effect of dronedarone is attributed to cardioprotective properties, possibly through attenuation of calcium overload during myocardial ischemia/reperfusion.
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