Pivotal role of the sympathetic nerves of the human heart in mental stress responses and triggered cardiovascular catastrophes

Mental stress can trigger cardiac catastrophes, explicitly evident during national disasters such as earthquakes. Activation of the cardiac sympathetic outflow and inhibition of the cardiac vagus are important mediating mechanisms. This manuscript describes efforts by the Human Neurotransmitters Research Laboratory of the Baker Institute in Melbourne to develop investigative methods to study the sympathetic nerves of the human heart, and to apply these in mental stress research. With laboratory mental stress, activation of the adrenal medulla was found to occur, accompanied by a regionalized sympathetic nervous response directed to the heart, but sparing the sympathetic outflow to the skeletal muscle vasculature. Patients with panic disorder are at increased cardiovascular risk. They exhibit high-level sympathetic activation during a panic attack, sometimes accompanied by coronary artery spasm. Patients with sudden ventricular arrhythmias causing collapse in the community were found to have as the predisposing substrate high baseline cardiac sympathetic activity, from previously unrecognized mild heart failure; it was surprising at the time that we did not find critical coronary artery stenosis as the substrate. In some the arrhythmia event had a behavioural trigger. In Takotsubo cardiomyopathy ("Broken Heart Syndrome") the myocardial stunning appears to represent a catecholamine cardiomyopathy, from astronomically high plasma adrenaline concentrations, rather than be caused by activation of the cardiac sympathetic nerves. Some diseases (essential hypertension, heart failure, panic disorder) have forms of sympathetic neural enhancement which contribute to cardiovascular risk: reuptake of noradrenaline by sympathetic nerves after release is faulty and single sympathetic fibres fire in multiple salvos within a single cardiac cycle. Paradoxically, obesity-hypertension does not share in this sympathetic neural augmentation, which is present only in normal-weight hypertensive patients, providing the possible basis for an observed "Obesity Paradox" (longer survival in obesity-hypertension than in normal weight hypertension). Community-wide specific prevention of cardiovascular triggering is not currently possible, due to there being no available simple screening tests which could be applied to the community at-large for the commonest substrates, silent coronary artery disease and mild heart failure. Standard medical preventive measures for coronary atherosclerosis will of course be helpful. Targeted prevention of triggering can be done in those with a detected predisposing substrate, such as genetic Long QT Syndrome, and in survivors of a serious triggered event, who need detailed, appropriate testing.