Lipopolysaccharide and sepsis-associated myocardial dysfunction

Myocardial dysfunction in sepsis demonstrates acute reduction in left-ventricular function that is potentially reversible yet also associated with increased mortality. The purpose of this review is to discuss the most recent advances in the current knowledge regarding the pathophysiological mechanisms of septic cardiomyopathy.

There are numerous candidate pathophysiologic mechanisms for the induction of myocardial dysfunction in sepsis. Sarcolemmal and myofibrillar damage to septic rat cardiomyocytes has been observed, and is likely related to oxidative stress. In a septic chimeric murine model, wild-type mice had decreased cardiac function and increased myocardial TNF-α and IL-6 levels whereas TLR-4 knockout mice had attenuated responses to lipopolysaccharide challenge; thus contributing to the increasing evidence for TLR-4's role in the myocardial inflammatory response to lipopolysaccharide. A similar finding regarding endothelial cell NF-κβ signaling inhibition was found using knockout mice.

Septic cardiomyopathy is a significant morbid component of severe sepsis and septic shock. Further research into reducing cardiomyocyte damage via oxidative stress, reducing pro-inflammatory responses induced by TLR-4/NF-κβ signaling, decreasing mitochondrial dysfunction, and improving cellular respiration thereby decreasing apoptosis are examples of areas that may be future therapeutic targets.