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alpha-Adrenergic receptors and coronary spasm: an elusive link
Insights
This study on variant angina found no evidence of increased sympathetic nervous system activity preceding coronary spasm. These findings suggest localized alpha-stimulation, not systemic sympathetic activation, may cause coronary artery spasm.
Area of Science:
- Cardiology
- Pharmacology
- Autonomic Nervous System
Background:
- Coronary artery spasm, a cause of variant angina, is thought to be linked to alpha-adrenergic receptors.
- The role of sympathetic nervous system activation in coronary spasm remains debated.
Purpose of the Study:
- To investigate the role of coronary alpha-adrenergic receptors in the development of coronary spasm.
- To determine if increased sympathetic outflow precedes episodes of ischemia in patients with variant angina.
Main Methods:
- Continuous Holter monitoring with electrocardiogram analysis to assess cardiac sympathetic activation.
- Provocative testing using cold pressor test, phenylephrine, norepinephrine, and ergonovine maleate.
- Pharmacological blockade with phentolamine to evaluate alpha-adrenergic receptor involvement.
Main Results:
- No significant increase in heart rate or corrected QT interval was observed before coronary spasm episodes.
- Ischemic episodes showed a higher incidence in the early morning, a period of low sympathetic activity.
- Ergonovine maleate consistently induced coronary spasm, while other provocative tests were largely negative.
- Phentolamine did not significantly reduce the frequency of ischemic attacks.
Conclusions:
- Increased sympathetic outflow to the heart does not appear to play a major role in the genesis of coronary spasm.
- The findings suggest that localized alpha-stimulation of epicardial arteries may be responsible for coronary spasm.
- Further research is needed to elucidate the precise mechanisms of coronary artery spasm.
Abstract:
In 14 consecutive patients with variant angina we investigated the possible role of coronary alpha-adrenergic receptors in the genesis of coronary spasm. In eight patients, computerized, beat-by-beat analysis of the electrocardiogram recorded during continuous Holter monitoring failed to reveal any increase of heart rate and corrected QT interval (both indexes of cardiac sympathetic activation) in the period preceding the onset of ST segment changes in 197 episodes of ischemia caused by coronary spasm. In the same patients, analysis of the circadian distribution of ischemic episodes revealed a significantly higher incidence in the early morning hours, when sympathetic activity is at the lowest level. Twelve patients underwent serial provocative testing with cold pressor, phenylephrine, or norepinephrine infusion and administration of ergonovine maleate. Ergonovine consistently reproduced coronary spasm in all 12 patients, while results of cold pressor testing were positive in only one. Infusion of phenylephrine (eight patients) or norepinephrine after beta-blockade (four patients) failed to precipitate myocardial ischemia. In five patients infusion of phentolamine at the highest tolerated dose did not reduce significantly the number of ischemic attacks when compared with placebo. In contrast to results of previous reports, our data seem to rule out the hypothesis that an increase of sympathetic outflow to the heart plays an important role in the genesis of coronary spasm. We cannot, however, exclude the possibility of localized alpha-stimulation of epicardial arteries.