a-murine-closed-chest-model-of-myocardial-ischemia-and-reperfusion

A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion

Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ...

University of Bonn, Germany

Pretreatment with low-dose lipopolysaccharide protects cells/organs against a subsequent lethal Gram-negative (lipopolysaccharide tolerance) or Gram-positive (cross tolerance) stimulus. We determined whether this occurs in the rat lung. The involvement of inducible nitric oxide synthase and heme oxygenase-1 was evaluated.

Inducible nitric oxide synthase and heme oxygenase-1 in the lung during lipopolysaccharide tolerance and cross tolerance.

Myocardial function is severely compromised during sepsis. Several underlying mechanisms have been proposed. The innate immune system, i.e. toll-like receptor (TLR) 2 and 4, significantly contributes to cardiac dysfunction. Little is known regarding TLR9 and its pathogenic ligand bacterial DNA in the myocardium. We therefore studied the role of TLR9 in myocardial inflammation and cardiac contractility.

Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of toll-like receptor 9.

Toll-like receptor 4 (TLR4) recognizes lipopolysaccharides and endogenous ligands released after organ injury. Deficiency of TLR4 attenuates the development of left ventricular hypertrophy after transverse aortic constriction (TAC) in mice. We hypothesized that application of the TLR4 antagonist eritoran may also reduce cardiac hypertrophy after TAC surgery.

The toll-like receptor 4-antagonist eritoran reduces murine cardiac hypertrophy.

Severe sepsis and septic shock are often accompanied by acute cardiovascular depression. Lipopolysaccharide (LPS) signaling via Toll-like receptor 4 (TLR4) can induce septic organ dysfunction. The aim of this study was to elucidate the in vivo impact of pharmacological TLR4 antagonism on LPS-induced cardiovascular depression using eritoran tetrasodium (E5564). To simulate sepsis, C3H/HeN mice were challenged i.p. with 2 mg/kg body weight LPS. With the intent to antagonize the LPS effects, eritoran was administered i.v. (4 mg/kg body weight). Physical activity, peripheral blood pressure, and heart frequency were recorded before and after LPS and eritoran injection. In addition, intracardiac hemodynamic parameters were analyzed with a pressure conductance catheter. After 2 and 6 h of LPS stimulation ± eritoran treatment, the hearts and aortae were harvested, and TLR as well as inflammatory mediator expression was measured using reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Lipopolysaccharide significantly decreased arterial blood pressure over time. Administration of eritoran partially prevented the LPS-dependent reduction in blood pressure and preserved cardiac function. In addition, LPS increased the expression of CD14 and TLR2 in cardiac and aortic tissue. In aortic tissue, eritoran attenuated this increase, whereas no significant reduction was observed in the heart. Furthermore, cardiac and aortic inducible nitric oxide synthetase mRNA levels were significantly increased 6 h after LPS application. This effect was reduced in the presence of eritoran. In summary, the beneficial influence of eritoran on cardiovascular function in vivo seems to rely mainly on reduction of LPS-induced inducible nitric oxide synthetase expression as well as on attenuated cytokine expression in the vascular wall.

Article	Year
Transfusion medicine reviews\| PubMed ID: 16787830	2006
The Journal of clinical endocrinology and metabolism\| PubMed ID: 17473064	2007
Shock (Augusta, Ga.)\| PubMed ID: 17505302	2007
Biological chemistry\| PubMed ID: 17516851	2007
Critical care medicine\| PubMed ID: 17522584	2007
Inducible nitric oxide synthase and heme oxygenase-1 in the lung during lipopolysaccharide tolerance and cross tolerance. Critical care medicine\| PubMed ID: 17901834	2007
Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of toll-like receptor 9. Cardiovascular research\| PubMed ID: 18194990	2008
Critical care medicine\| PubMed ID: 18664807	2008
Frontiers in bioscience : a journal and virtual library\| PubMed ID: 19273249	2009
Critical care medicine\| PubMed ID: 20081527	2010
Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 21057083	2010
Critical care (London, England)\| PubMed ID: 21466684	2011
The toll-like receptor 4-antagonist eritoran reduces murine cardiac hypertrophy. European journal of heart failure\| PubMed ID: 21613426	2011
In vivo Toll-like receptor 4 antagonism restores cardiac function during endotoxemia. Shock (Augusta, Ga.)\| PubMed ID: 22089127	2011

Olaf Boehm

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