Impaired sarcoplasmic reticulum function in lipopolysaccharide-induced myocardial dysfunction demonstrated in whole heart.

To clarify the pathophysiological cascade leading to lipopolysaccharide- (LPS) induced myocardial dysfunction, we measured sarcoplasmic reticulum (SR) function, expression of inducible nitric oxide synthase (iNOS), and left ventricular (LV) function in a rat whole heart model. The LV function was evaluated by peak LV pressure and SR function was evaluated by the mechanical restitution (MR) curve, a physiological parameter of SR function. The mechanical restitution curve was constructed by plotting extrasystolic potentiation of LV dP/dt during extrasystoles (100-700 ms) under fixed pacing. Functions were evaluated using the perfusion apparatus at 6 or 24 h after LPS administration. In the 6 h group, LV pressure was depressed to 62% of the control, the SR function was impaired, and iNOS protein was expressed. In the 24 h group LV pressure and SR function remained at the control levels, iNOS was not detected. In the 6 h group dexamethasone co-administration normalized the LPS effect and iNOS was not expressed. LPS-induced myocardial dysfunction appeared to be caused by impaired SR function and NO expression suggesting that NO may act as a trigger.