Adrenergic Overstimulation

To the Editor:

We read with great interest the paper by Martin et al¹ about septic cardiomyopathy in a recent issue of CHEST (February 2019). In particular, we were impressed by the examination of the etiopathologic mechanisms of sepsis-related cardiomyopathy. However, we think the effect produced by adrenergic stimulation in determining cardiac dysfunction in patients with sepsis has not been addressed. Continuous adrenergic overstimulation constitutes, in the stage immediately after the initial compensation phase, an activation of beta-1 receptors. These receptors, through the mediation of cytokines and, above all, an increased inflow of intracellular calcium, determine the initiation of apoptotic pathways.² Moreover, the continuous adrenergic stimulation determines a downregulation of the beta receptors, which decrease in density on the wall of myocytes. These mechanisms could be at least partly mediated by molecules known for their effects on myocardial depression, such as inducible nitric oxide. The most studied stimulus is the lipopolysaccharide endotoxin produced by gram-negative bacteria.³ We think highlighting this hypothesis could be extremely important for several reasons. First of all, studying this model would probably allow us to better understand not only the damage mechanisms induced by sepsis, but also those produced by equally harmful syndromes, such as burns, trauma, and so forth. Moreover, if this hypothesis were to be confirmed by clinical trials, it would explain the reason for nonresponse to catecholamines by some patients with sepsis and, above all, would allow for use of different and perhaps more effective therapeutic strategies for sepsis. In fact, some preliminary studies have shown a beneficial effect on survival by beta-blocking drugs such as, for example, esmolol.^{3, 4} We therefore think that discussing it in the article would have allowed the authors a better and clearer analysis on sepsis-related cardiomyopathy.