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.
Hoshiai
M
M
Department of Physiology, School of Medicine, Tokai University, Kanagawa, Japan.
Hattan
N
N
Hirota
Y
Y
Hoshiai
K
K
Ishida
H
H
Nakazawa
H
H
D000818:Animals; D001696:Biomechanical Phenomena; D003907:Dexamethasone / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced*
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat