Myocardial dysfunction in early state of endotoxemia role of heme-oxygenase-1.
BACKGROUND
The triggers and cellular mechanisms of cardiac dysfunction have not been clearly established during the early period following challenge with lipopolysaccharides (LPS) (<1 h post-LPS). The aim of the study was to evaluate the myocardial depression during early stage of endotoxemia, the relationship between oxidative stress production and cardiac dysfunction in a rat model of endotoxic shock, and its inhibition by heme-oxygenase-1 (HO-1) overexpression.


METHODS
LPS-induced myocardial deformation was assessed by tissue Doppler imaging and invasive hemodynamic measurements in rats 2 h after LPS challenge. Myocardial samples were processed for the measurements of tumor necrosis factor alpha (TNFalpha), nitric oxidase synthase II (NOSII), HO-1 gene expression, reactive oxygen species (ROS) production, and reduced glutathione/oxidized glutathione (GSH/GSSH) ratio.


RESULTS
Myocardial systolic and diastolic deformation was evident as determined by tissue Doppler imaging but left ventricular conventional echocardiographic parameters did not show significant alterations. Myocardial deformation was significantly associated with reactive oxygen species and TNFalpha overproduction. Pretreatment with hemin to induce HO-1 resulted in decreased oxidative stress and TNFalpha production, and prevented LPS-induced alterations in myocardium.


CONCLUSIONS
These preliminary results suggest myocardial alteration at a very early stage after LPS challenge associated with oxidative stress response. Manipulation of the HO-1 pathway may represent a future therapeutic strategy to counteract oxidative stress of endotoxemia and perhaps may limit future myocardial deformation.
Tamion
Fabienne
F
Inserm (Institut National de la Santé et de la Recherche Médicale) Rouen University Medical School, Rouen, France. fabienne.tamion@chu-rouen.fr
Bauer
Fabrice
F
Richard
Vincent
V
Laude
Karine
K
Renet
Sylvanie
S
Slama
Michel
M
Thuillez
Christian
C
D000818:Animals; D004452:Echocardiography; D019446:Endotoxemia / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D006439:Hemodynamics; D008297:Male; D009206:Myocardium / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D016277:Ventricular Function, Left
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D006427:Hemin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat