Sex Differences in Cardiac Electrophysiology

In recent years there has been more focus on investigating sex differences across all medical fields, including cardiology. There are sex differences in disease presentation, treatment and baseline function. These differences are critical to understand in order to properly treat both men and women. Even with an increased focus on this field, research has a male bias and there is more work to be done. Cardiac conduction is a highly synchronized process. Electrical signals are passed cell to cell through two mechanisms, ephaptic coupling and gap junctional coupling. These methods of electrical communication rely on gap junctions, sodium channels and the perinexus. When conduction is disrupted it causes arrhythmias. When investigating these three critical determinants of cardiac conduction in guinea pig hearts, we determined that there are sex differences in two of three investigated determinants. It appears that females are more susceptible to sodium channel modulation while males are more susceptible to gap junction modulation. Understanding these differences is critical to clinical care. It has been shown that females have higher mortality following cardiothoracic surgery and the reason for this is unknown. During cardiothoracic surgery the heart is arrested and maintained by a fluid, cardioplegia solution. Cardioplegia solutions contain components that are known to modulate conduction. We investigated the sex differences in cardiac electrophysiology with a focus on cardiac conduction and components of a common cardioplegia solution; we determined that there are electrophysiologic sex differences in response to both magnesium and mannitol.
The sex substrates in three of the major determinants of conduction (sodium channels, gap junctions and perinexal width) and the differences in the effects of cardioplegia components on males and females may help to explain the higher mortality of females post cardiothoracic surgery.