Oxytocin Effects on Cardiac Electrophysiology
Condition: Cardiac Arrhythmia
MeSH terms: Arrhythmias, Cardiac
Study type: Interventional
Phase: Early Phase 1

Summary: 
      In this pilot study the investigators will perform a double-blind randomized trial of
      intranasal oxytocin on measures of cardiac refractoriness, among individuals who are
      undergoing clinically indicated catheter ablation procedures for paroxysmal atrial
      fibrillation. The investigators seek to enroll 20 patients for this study, for the purpose of
      estimating effect sizes for a larger future study.
    

Detailed description: 
      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.
    

Intervention name(s): Oxytocin; Saline
Intervention type(s): Drug; Other
Intervention description(s): Intranasal dose of 20 IU oxytocin; Intranasal dose of saline
Other intervention name(s): Pitocin
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Oxytocin; Arrhythmia