Myocardial dysfunction in severe sepsis and septic shock: More questions than answers?

The main motivation of the present review article was to raise some doubts and show that despite numerous studies and review articles that have been published on the subject of septic myocardial dysfunction, many questions central to its pathophysiology are still open. For instance, if sepsis per se causes significant systolic myocardial dysfunction, it is not clear how aggressive fluid loading, normally given to patients during resuscitation in septic shock, increases CO and induces the hyperdynamic cardiovascular state of septic shock in marked contrast to the situation in cardiogenic shock. Is it only the effect of increasing preload or massive fluid loading significantly decreases SVR, thus facilitating the increase in CO, and what is the effect of massive fluid loading on myocardial dysfunction? There is also no adequate explanation in the literature for the observations that patients with dilated left ventricles during septic shock survive better than patients with smaller ventricles. One possible explanation is that diastolic dysfunction impairs ventricular dilatation and prevents the necessary increases in SV and CO in response to sepsis and fluid loading. However, what causes diastolic dysfunction? Is it a condition inherent to the patient's heart or develops as a result of sepsis or therapy for sepsis? Too little is known yet on septic diastolic dysfunction. Also, in the molecular/cellular level, numerous mechanisms have been proposed to lead to myocardial dysfunction; however, no single molecule or mediator has been found to have a central or necessary role in the development of septic myocardial dysfunction. These unresolved questions leave room for further clinical and experimental investigations.