Heme oxygenase/carbon monoxide system and cardiac conduction system.

FactsThe heme oxygenase/carbon monoxide system is required for cardiomyocyte development.Developing cardiomyocytes experience fluctuating oxygen levels. Heme oxygenase-1, which is induced by hypoxia, protects the cardiomyocytes.Heme oxygenase activity and its products influence biochemical processes through transcription factors that are needed for cardiac development.The cells of the cardiac conduction system are specialized cardiomyocytes that are modified for electrical signaling, not contraction.Carbon monoxide modulates vascular tone and inflammation, and protects against oxidative stress. It is required to maintain the health and function of the cardiac conduction system.Open QuestionsHow do the effects of the heme oxygenase/carbon monoxide system differ between contractile and cardiac conduction system cardiomyocytes?Are the effects of the heme oxygenase/carbon monoxide system different for the different structures of the cardiac conduction system (sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje fibers)?Is carbon monoxide a biomarker for cardiac conduction system abnormalities? If so, can it be used for risk stratification?How can the heme oxygenase/carbon monoxide system be used to treat cardiac conduction system abnormalities?What cardiac conduction abnormalities occur if heme oxygenase-1 is lacking during in utero development? The heme oxygenase/carbon monoxide system is well-established as a critical regulator of contractile cardiomyocyte development. Although the heme oxygenase/carbon monoxide system is known to have protective effects against arrhythmias by reducing oxidative stress and preserving mitochondrial function in general myocardium, its specific impact on components of the cardiac conduction system, such as the sinoatrial and atrioventricular nodes, is unclear. On the one hand, the antioxidant and anti-inflammatory properties of the heme oxygenase/carbon monoxide system are believed to help maintain normal electrical conduction and prevent arrhythmias. On the other hand, pathological conditions such as age-related sick sinus syndrome have been linked to dysfunction of the heme oxygenase/carbon monoxide system, even though carbon monoxide is detrimental at toxic levels. This review synthesizes the current evidence on the dual nature of the heme oxygenase/carbon monoxide system in the cardiac conduction system. This review highlights the critical need for further investigation of the heme oxygenase/carbon monoxide system's physiological roles and therapeutic potential for conduction pathologies.