Oxytocin Effects on Cardiac Electrophysiology

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.

Inclusion Criteria:

- Males and females older than 18 and younger than 85 years of age

- Undergoing catheter ablation for paroxysmal atrial fibrillation

- Presenting in sinus rhythm at the time of their procedure

Exclusion Criteria:

- Left ventricular ejection fraction <0.40

- Paced rhythm >50 percent of the time by device interrogation if a pacemaker is
present