LPS pretreatment ameliorates peritonitis-induced myocardial inflammation and dysfunction: role of myocytes

Abstract

Peritonitis induced by cecal ligation and puncture (CLP) produces a systemic inflammatory response that can be largely mitigated by pretreatment of the animals with lipopolysaccharide (LPS tolerance). Although cells of myeloid origin and endothelial cells have been shown to contribute to the development of LPS tolerance, little is known regarding the potential role of parenchymal cells in this phenomenon. The major aim of the present study was to assess whether cardiac parenchymal cells (myocytes) contribute to the development of LPS tolerance. Six hours after induction of CLP rats were neutropenic and acidotic, the myocardium contained a leukocyte infiltrate [myeloperoxidase (MPO) activity was increased], and myocardial contractile function was impaired (left ventricular developed pressure was decreased). In animals that were pretreated with LPS these manifestations of sepsis were largely reversed. Further studies focused on the responses of cardiac myocytes to CLP and whether myocytes contributed to the development of LPS tolerance. Myocytes were isolated from rat hearts 6 h after induction of CLP. These myocytes 1) exhibited an impaired ability to shorten in response to pacing, 2) contained the nuclear transcription factor NF-κB in their nuclei, 3) increased their surface levels of intercellular adhesion molecule-1 (ICAM-1), and 4) were hyperadhesive for neutrophils. All of these events did not occur in myocytes obtained from animals that were pretreated with LPS before induction of CLP. These findings indicate that LPS tolerance can be induced in myocytes with respect to polymorphonuclear leukocyte adhesion, presumably by an inability of CLP to mobilize NF-κB to the myocyte nuclei and, thereby, preventing an increase in surface levels of ICAM-1.

Cleavage of IκBα by calpain induces myocardial NF-κB activation, TNF-α expression, and cardiac dysfunction in septic mice

“…Myocardial contractile function was studied using a modified Langendorff isolated heart preparation, as previously described (22). Briefly, after heparinization and ether anesthesia, mouse hearts were rapidly excised and placed into ice-cold Krebs-Henseleit (KH) buffer solution.…”

Investigation of the effect of silymarin on the liver in experimental sepsis

“…On the other hand, cytokines are known to peak up to this time point, causing free radical formation and oxidative tissue injury (27). The early effects of sepsis and antioxidant treatment on liver tissue were investigated in the present study.…”

“…Therefore early stage of sepsis (6 hr) was chosen for preventing the organ damage at the beginning of sepsis. Sepsis is associated with the development of progressive damage in multiple organ systems remote from the locus of infection (27). There is an increasing evidence that oxidative stress has an important role in the development of sepsis-induced multiorgan failure (28).…”

Role of the cholinergic anti-inflammatory pathway in endotoxemia-induced multi-organ damage in the rat

“…Endotoksin inflamatuvar hücreleri aktive ederek inflamatuvar yanıtın daha da şiddetlenmesine yol açan pro-inflamatuvar sitokinlerin (TNF-α, IL-1β gibi) serbestlenmesine neden olmaktadır. Bu inflamatuvar kaskad lökositlerin çeşitli organlara infiltrasyonuna ve buna bağlı olarak vasküler ve parenkimal hücre disfonksiyonuna yol açmaktadır (27). Çalışmamızda, tedavisiz sepsisli grupta karaciğer, böbrek ve akciğer örneklerinde mikroskobik düzeydeki hasarın lipid peroksidasyonda artış ve endojen antioksidan glutatyonda azalma ile birlikte olduğu görül-mektedir.…”