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Cardiac Sympathetic Nerve Biology and Brain Monoamine Turnover in Panic Disorder
aBaker Heart Research Institute, Melbourne, Australia bSchool of Primary Care and Department of General Practice, Monash University, Melbourne, Australia cDepartment of Pharmacology, University of Melbourne, Melbourne, Australia d37 Brunswick Street, Fitzroy, Melbourne, Australia
Address for correspondence: Prof. Murray Esler, Baker Heart Research Institute, PO Box 6492, St. Kilda Road Central, Melbourne, Victoria 8008, Australia. Voice: (61) 3 8532-1338; fax: (61) 3 8532-1100. e-mail: murray.esler{at}baker.edu.au Ann. N.Y. Acad. Sci. 1018: 505-514 (2004).
Panic disorder serves as a clinical model for testing whether mental stress can cause heart disease. Our own cardiologic management of panic disorder provides case material of recurrent emergency room attendances with angina and electrocardiogram ischemia, triggered arrhythmias (atrial fibrillation, ventricular fibrillation), and documented coronary artery spasm, in some cases with coronary spasm being complicated by coronary thrombosis. Application of radiotracer catecholamine kinetics and clinical microneurography methodology suggests there is a genetic predisposition to panic disorder that involves faulty neuronal norepinephrine uptake, possibly sensitizing the heart to symptom generation. During panic attacks there are large sympathetic bursts, recorded by clinical microneurography in the muscle sympathetic nerve neurogram, and large increases in cardiac norepinephrine spillover, accompanied by surges of adrenal medullary epinephrine secretion. In other conditions such as heart failure and presumably here also, a high level of sympathetic nervous activation can mediate increased cardiac risk. The sympathetic nerve cotransmitter, neuropeptide Y (NPY), is released from the cardiac sympathetics during panic attacks, an intriguing finding given that NPY can cause coronary artery spasm. There is ongoing, continuous release of epinephrine from the heart in panic sufferers, perhaps attributable to epinephrine loading of cardiac sympathetic nerves by uptake from plasma during panic attacks, or possibly to in situ synthesis of epinephrine through the action of intracardiac phenylethanolamine-N-methytransferase (PNMT) activated by repeated cortisol responses. We have used internal jugular venous sampling and measurement of overflowing lipophilic brain monoamine metabolites to quantify brain norepinephrine and serotonin turnover in untreated patients with panic disorder. We find normal norepinephrine turnover but a marked increase in brain serotonin turnover in patients with panic disorder, in the absence of a panic attack, which presumably represents an underlying neurotransmitter substrate for the condition.
Key Words: mental stress • heart risk • neuropeptide Y • sympathetic cotransmission • serotonin This article has been cited by other articles:
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