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Altered adrenergic activity in coronary arterial spasm: insight into mechanism based on study of coronary
Insights
Sympathetic nervous system alterations, specifically asymmetric stellate ganglion activity and alpha-adrenergic stimulation, may trigger coronary arterial spasm in some patients. Alpha-adrenergic blockers effectively reversed spasm and relieved symptoms.
Area of Science:
- Cardiology
- Neuroscience
- Pharmacology
Background:
- Coronary arterial spasm is a significant cause of angina.
- The underlying pathophysiologic mechanisms are not fully understood.
- The role of sympathetic nervous system activity in coronary spasm requires further investigation.
Purpose of the Study:
- To investigate the hypothesis that altered sympathetic activity contributes to coronary arterial spasm.
- To examine the effects of alpha-adrenergic blockade on coronary hemodynamics and electrocardiographic changes in patients with coronary spasm.
Main Methods:
- Measurement of coronary vascular resistance and coronary sinus blood flow using thermodilution.
- Administration of intravenous phentolamine (alpha-adrenergic blocker).
- Administration of oral phenoxybenzamine (long-acting alpha-adrenergic blocker).
- Electrocardiographic monitoring, including corrected Q-T interval and T wave analysis.
- Provocation of spasm using ergonovine maleate in some patients.
Main Results:
- Coronary arterial spasm increased coronary vascular resistance by 107%.
- Intravenous phentolamine acutely reversed coronary spasm and reduced coronary resistance.
- Long-term phenoxybenzamine treatment resolved symptoms in four patients.
- Transient Q-T interval prolongation preceded spasm in variant angina patients.
- T wave abnormalities normalized with isoproterenol and phenoxybenzamine.
Conclusions:
- Alterations in sympathetic nervous system activity, including asymmetric stellate ganglion activity and alpha-adrenergic stimulation, may predispose to coronary arterial spasm.
- Alpha-adrenergic blockade is a potential therapeutic strategy for managing coronary arterial spasm.
- Electrocardiographic changes, such as Q-T interval prolongation, may serve as indicators of underlying sympathetic dysregulation in coronary spasm.
Abstract:
To elucidate the pathophysiologic mechanism of coronary arterial spasm, the hypothesis was examined that underlying alterations in sympathetic activity may account for this syndrome in some patients. Observations were directed to alterations in coronary arterial hemodynamics and the electrocardiogram. Spasm of the left anterior descending coronary artery produced a mean increase in coronary vascular resistance of 107 percent (P less than 0.05) in four patients in whom coronary sinus blood flow was measured with the thermodilution technique. The alpha adrenergic blocking agent phentolamine, given intravenously, acutely reversed coronary spasm and its clinical manifestations in eight patients and reduced coronary resistance. In four patients, administration of the long-acting oral alpha blocking agent phenoxybenzamine (20 to 80 mg/day) caused disappearance of symptoms during a follow-up period of 3 to 12 months. Transient prolongation of the corrected Q-T interval preceded spontaneous or ergonovine maleate-provoked coronary spasm in 11 patients with variant angina pectoris, whereas no significant change in the Q-T interval followed ergonovine administration in 27 control patients with atypical chest pain who did not have coronary spasm. T wave inversions in the resting electrocardiogram were normalized by isoproterenol infusion in one patient and by long-term phenoxybenzamine treatment in four patients with variant angina pectoris. These Q-T and T wave changes are analogous to those described with unilateral or asymmetric stellate ganglion stimulation in animals. These observations suggest that alterations in the sympathetic nervous system that are consistent with asymmetric stellate ganglion activity and transient alpha adrenergic receptor stimulation can presage the development of coronary arterial spasm in some patients with variant angina pectoris.