in the previous issue of critical care , joulin and colleagues   describe an animal model of lipopolysaccharide ( lps)-induced impaired myocardial systolic and diastolic function . diastole is composed of two physiological phenomena : myocardial stiffness , which is energy independent , and active relaxation , which is an atp - requiring process . current echocardiographic techniques can help distinguish which of the two is the predominant pathway , although these techniques may not always be practical in critically ill patients . in some patients with sepsis , a reversible component to impaired ventricular relaxation has been demonstrated , which would imply that the energy - requiring component of diastolic function is more perturbed in certain patients . one might wonder why this is an important distinction to make , but considering that increased mortality in sepsis may be correlated with increasing fluid administration , it would seem that being able to distinguish between isolated systolic , diastolic , or combined dysfunction may prove to be life saving . this was achieved by serial transesophageal echocardiographic measurement of standard indices of systolic function , as well as analyzing diastolic mitral inflow and annular tissue doppler patterns , the current standard in echocardiographic grading of diastolic function . this study highlighted the fact that we should be cognizant that not all patients suffering from sepsis and shock should be treated uniformly , and that choices of intravenous resuscitation and vasopressor therapies need careful consideration . the study further elucidated the reversible nature of the impaired ventricular relaxation in humans , suggesting that a metabolic or molecular process may be responsible . an attractive mechanism currently thought to play a major role is that of calcium flux . systole is initiated by rapid elevation of myocyte intracellular calcium , both through influx ( through l - type calcium channels ) and calcium - mediated calcium release from the sarcoplasmic reticulum ( through the ryanodine receptor ) . re - uptake of calcium into the sarcoplasmic reticulum by sarcoplasmic reticulum ca - atpase ( serca ) allows for cardiac relaxation . the ability of serca to pump calcium back into the sarcoplasmic reticulum is governed by phospholamban , a sarcoplasmic reticulum membrane - bound modulatory protein . the rapidity at which calcium is returned to the sarcoplasmic reticulum is directly related to the rapidity of cardiac relaxation . in the unphosphorylated state signaling by protein kinase leads to phosphorylation of phospholamban , which , in turn , diminishes its inhibitory activity on serca , promoting cardiac relaxation . in a knockout mouse model lacking phospholamban , while other pathways , such as sodium - calcium exchange , are important in myocardial calcium trafficking , those are currently beyond the scope of this comment , and will not be described . joulin and colleagues , in their experiments , were able to demonstrate a serca - dependent aberration in diastolic cardiomyocyte behavior . in particular , in their experiments , they were able to demonstrate a serca - dependent aberration in diastolic cardiomyocyte behavior . the force - frequency relationship ( that is , heart - rate - dependent increase in cardiomyocyte shortening ) and frequency - dependent acceleration of relaxation are physiological phenomena that ensure maintenance of cardiac output with the decreased ejection and filling times that are consequences of higher heart rates . the group hypothesized that lps would disrupt this delicate balance by exerting an effect on the molecular workings within the cardiomyocyte  principally through the inhibition of the phosphorylation of phospholamban . by utilizing echocardiographic measurements of diastole , and through western blot analyses , they were able to demonstrate a correlation between lps - induced myocardial relaxation dysfunction ( frequency - dependent acceleration of relaxation depression ) and serca function . it is important to note that this work was done in a murine model of lps infusion , a model with potentially important differences from septic patients being treated in the intensive care unit . anesthetic agents were used to regulate heart rates , and real - time alterations in physiological functioning may have been missed . the group studied only the sarcoplasmic reticulum when calcium trafficking is also linked to mitochondrial function and integrity , nitric oxide production , the beta - adrenergic response , and potential protective effects on the myocardium during prolonged sepsis . would specific targeting of intracellular calcium , or serca - related protein kinase and phosphatase result in better hemodynamics in septic shock ? there is already a body of evidence to suggest that calcium - sensitizing agents , such as levosimendan , may improve hemodynamics in sepsis . in two animal models , left ventricular relaxation was improved after treatment with levosimendan in contrast to inotropes , such as milrinone or dobutamine , and in a clinical trial , levosimendan proved useful in improving global hemodynamic measurements . the study by joulin and colleagues is certainly thought provoking , and will hopefully lead us closer to developing better strategies for dealing with sepsis - induced myocardial dysfunction  both its systolic and diastolic components .