Pilot Study of Intranasal Oxytocin and Cardiac Electrophysiology in Humans

Despite widespread advances in the treatment of coronary artery disease and the growing use of automated external defibrillators and implantable cardioverter-defibrillators (ICDs) to treat ventricular arrhythmias, sudden cardiac death (SCD) due to ventricular arrhythmia remains a major public health problem. National estimates of SCD or out-of- hospital cardiac arrest range from 400,000 to 450,000 events annually. Although cardiac mortality rates have declined over time, the proportion of cardiac deaths that are sudden has increased during a time when major advances in device therapy for the prevention and treatment of SCD have taken place. This unfavorable trend is a consequence of the inability to accurately identify those who will die suddenly from a lethal ventricular arrhythmia and to disseminate effective preventive strategies for populations at risk.

Observational evidence has indicated that depression is associated with risk of SCD, both in patients with coronary artery disease as well as in individuals without heart disease. In patients with ICDs, depressive symptoms are associated with increased risk of shocks for ventricular arrhythmia, suggesting that ventricular arrhythmia is more common in depressed individuals. A leading candidate mechanism that may account for the association between depression and ventricular arrhythmia involves cardiac autonomic dysfunction; for instance, multiple studies have shown that depressed individuals have abnormal heart rate variability.

Recent evidence has emerged about the potential importance of oxytocin in the cardiovascular response to stress and depression. Oxytocin is a 9-amino acid peptide that is produced in the hypothalamus and released into the central nervous system and the bloodstream. Oxytocin has both hormone and neurotransmitter function, and affects targets including the hypothalamus, amygdala, hippocampus, brainstem, heart, uterus, and regions of the spinal cord that regulate the autonomic nervous system. Polymorphisms of the oxytocin receptor have been associated with improved cardiovascular responses to laboratory stress in humans.

Exogenous administration of intravenous oxytocin in a prairie vole model of isolation has been shown to protect against the heart rate response to social isolation and to improve heart rate variability. In addition, intranasal oxytocin administered to humans augments both sympathetic and parasympathetic modulation of the heart rate. Initial studies of intravenous oxytocin demonstrated direct effects on cardiac arrhythmias in animal models, even including termination of ventricular fibrillation, suggestive of a quinidine-like action on myocardial excitability. However, administration of intravenous oxytocin in women after delivery has been associated with abnormalities in cardiac repolarization and even with induced ventricular arrhythmia. Therefore, although there is reason to believe that administration of exogenous oxytocin may affect the probability of arrhythmia, the direction of this impact is unclear.