An endocrine hypothesis for the genesis of atrial fibrillation: the hypothalamic-pituitary-adrenal axis response to stress and glycogen accumulation in atrial tissues.

backgroundThe underlying role of intracellular glycogen in atrial fibrillation is unknown. Experimental models developed in the goat have shown an increase of intracellular glycogen concentration in atrial myocytes resulting from prolonged pacing induced atrial fibrillation (AF). These observed glycogen molecules are as a result of structural remodeling and are known to replace the intracellular myofibrils causing myolysis in studies done in different animal models. The accumulation of glycogen is progressively and directly related to the duration of pacing-induced AF. Similar responses have been seen in clinically derived atrial tissues.

aimsWe intend to present an endocrine hypothesis supported by published evidence that stress acting through the hypothalamic-pituitary-adrenal axis (HPA) is a contributing metabolic factor responsible for the increase of glucose levels via the hormone cortisol. This excess glucose is then metabolized by the myocytes during each heart beat and stored as glycogen. A literature search was done, and published evidence supporting stress was shown to be the main factor for the formation of glucose leading to glycogen deposition to in the cardiac myocytes.

resultsStress on the HPA axis stimulates the adrenal glands to release the hormone cortisol in the blood stream; this in turn increases the cardiac tissue glycogen concentration. It is also known that during each beat, excess glucose is removed by the myocytes and stored as glycogen. As aforementioned, in the cardiac myocytes, dense glycogen content with/without loss of myofibrils has been detected in both human and animal models of AF.

conclusionsWe hypothesize that the increase of the intrinsic glycogen concentration and distribution is a result of a metabolic disruption caused by stress through the HPA Axis. For example, in atrial myocytes, the glycogen molecules impede the normal intercellular communications leading to areas of slow conduction favoring reentrant-based AF.