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Sepsis: going to the heart of the matter


Although myocardial depression is the predominant cause of death in severe sepsis/septic shock, it remains disputed whether the functional changes are consequential events following structural alterations. If we look at myocardial dysfunction from the perspective of a critically ill patient, there are a few questions to be asked: What causes this? What is the pathophysiology of cardiac dysfunction and death? Is there something that could be done to prevent the outcome? Each of these questions is interrelated and the answers will be more easily addressed if we continue to understand the basic mechanisms that are implicated. The principal mechanisms proposed for the pathogenesis of myocardial dysfunction support a prominent role for functional rather than anatomical abnormalities. However, attempts to reduce high mortality of septic patients by manipulating the functional alterations have provided limited success. In recent years the concept of septic cardiomyopathy has evolved, which implies alterations in the myocardium phenotype. This Review includes an overview on the activation of the immune system and therapeutic approaches in sepsis, myocardial structural changes in the human septic heart, experimental models of sepsis, and cellular, molecular and functional myocardial changes seen in a variety of experimental sepsis models. The abnormal parameters discussed may emerge as therapeutic targets, which modulation might provide beneficial effects on future cardiovascular outcomes and mortality in sepsis. (AU)

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