sepsis - induced cardiac dysfunction has been known for many years but the mechanism appears to be complex , including both ' intrinsic ' cardiomyopathy and direct and/or indirect effects of circulating depressing factors . among these factors , many cytokines have been suggested to play a role . in the previous issue of critical care , exosomes released by platelets were also suggested to play a role . the clue for the sepsis - induced cardiac dysfunction in patients with septic shock came from parker and colleagues ' study in 1984 . using simultaneous radionuclide cardiac imaging and thermodilution cardiac output studies on patients with septic shock , they showed a ' paradox ' : all patients had a high cardiac output and maintained a stroke volume index associated with a depressed left ventricular ejection fraction < 0.45 . interestingly , survivors had a left ventricular ejection fraction that remained low for 4 days and then rose to normal values within 710 days . these data reflecting left ventricular dysfunction but also right ventricular dysfunction were confirmed by further studies . it is now agreed that systolic function deteriorates in the early phase of septic shock in humans , as confirmed by echocardiographic studies . reduced compliance manifested as reduced rapidity of ventricular filling has been described in patients with septic shock . using left ventricular pressure  volume loops , we recently confirmed a reduced rate of left ventricular relaxation and decreased compliance in lipopolysaccharide - treated rabbits . both alterations can be restored , at least partially , by levosimendan but not by milrinone or dobutamine . in the 1970s and 1980s , the mechanism of sepsis - induced cardiac failure was thought to be the presence of ' myocardial depressant ' substances that directly alter heart function . parrillo and colleagues suggested the existence of ' circulating myocardial depressant factor(s ) ' in humans by showing that serum obtained during the initial phase of septic shock decreased both the amplitude and the velocity of shortening of cardiomyocytes from newborn rats . although cytokines such as tnf and il-1 have been suggested to be those ' circulating myocardial depressant factor(s ) ' and might explain a myocardial depressant activity in the first 2 days of sepsis , they can hardly explain a delayed and depressant effect on heart contractility observed 710 days later since tnf and il-1 plasma levels return to normal values within 48 hours of sepsis onset . in the study published in the current issue of the journal , azevedo and coworkers suggest that exosomes released by platelets and identified in the plasma might explain myocardial depression in sepsis . although these results should be confirmed by different groups in different settings , it is interesting to mention that this paper opens our eyes to a new concept that platelets may release , over days , exosomes that induce and maintain alterations of heart function in septic patients . it is interesting to mention that the duration of myocardial depression corresponds to the 10 days of life of the platelets . is this by chance or do the platelets present at the time of sepsis insult keep a footprint of the first injury for the remaining days of their life ? exosomes might act via free radical release . nitric oxide , produced mainly by inducible nitric oxide synthase 2 , nitric oxide plays also a crucial role in the development of the ' intrinsic ' septic cardiomyopathy in many ways , including a change in contraction , protein nitration and an alteration in mitochondrial respiration . in septic patients , nitric oxide produced in large amounts may interact with the superoxide anion and produce peroxynitrite . as suggested by our model of muscle dysfunction in septic patients , peroxynitrite  rather than nitric oxide per se  decreases muscle contractility . of interest , we recently showed in an animal model of sepsis that other cardiovascular mediators , such as prostaglandins and endothelin , released by cardiac endothelium , may contribute to restore cardiac contractile performance . azevedo and coworkers suggested that platelets might also be the source of these mediators . in summary , platelets might be a forgotten source of mediators that alter heart function during sepsis .
the mechanism of sepsis - induced cardiac failure was initially thought to be related to the presence of ' myocardial depressant ' substances that directly alter heart function . 
 exosomes released by platelets and identified in the plasma are suggested to , at least partially , explain myocardial depression in sepsis . 
 this hypothesis needs to be evaluated by clinical studies .