Objective: Myocardial dysfunction has been shown to play a major role in the mortality associated with sepsis. Tumor necrosis factor-α (TNF-α) has been implicated as a key factor in this dysfunction, and the sphingomyelin pathway is a membrane-signaling pathway by which TNF-α exerts many of its negative inotropic effects. The purpose of this manuscript is to review the physiology of TNF-α and sphingosine, etiology of increased levels of myocardial TNF-α and sphingosine, as well as the effects of these increased levels on the myocardium. In addition, both in vivo and in vitro studies looking at the effects of blocking TNF-α will be presented.
Data sources: Data sources included scientific reviews and original research publications.
Human data synthesis: It is well documented that levels of TNF-α are elevated in many human patients with sepsis. However, clinical trials evaluating the effects of blocking TNF-α have not shown a statistically significant decrease in the mortality of sepsis.
Veterinary data synthesis: No clinical research has been performed on TNF-α and myocardial dysfunction in veterinary medicine, although many of the research models may be relevant to our patient population. In these models, myocardial TNF-α and sphingosine are elevated in sepsis. Treatment of experimental animals with TNF-α antibodies has shown variable results, while blockage of sphingosine has been shown to completely reverse the myocardial effects of increased TNF-α.
Conclusions: Tumor necrosis factor-α and the sphingomyelin pathway are an important part of the myocardial compromise that accompanies sepsis. Further research into these pathways may provide new understandings and treatment options for veterinary patients.