The Effect of Lipopolysaccharide on Ischemic-Reperfusion Injury of Heart: A Double Hit Model of Myocardial Ischemia and Endotoxemia

Nader, Nader D.; Asgeri, Mehrdad; Davari-Farid, Sina; Pourafkari, Leili; Ahmadpour, Faraz; Porhomayon, Jahan; Javadzadeghan, Hassan; Negargar, Sohrab; Knight, Paul R.

doi:10.15171/jcvtr.2015.19

Cited by 8 publications

(4 citation statements)

References 25 publications

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“…It is well established that low doses of LPS can alleviate myocardial IRI due to activation of the inositol-requiring enzyme 1 and phosphoinositide 3-kinase/Akt signaling pathways [38,39]. However, high doses of LPS aggravate IRI and cause contractile dysfunction [40]. We presume that the significantly elevated LPS level in the DIO+CIC group resulted in a subthreshold injury to the heart, which neutralized the protective effect of TTC.…”

Section: Discussionmentioning

confidence: 82%

Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis

et al. 2019

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BackgroundRecent evidence suggests that antibiotic-induced changes in the composition of intestinal microflora, as well as the systemic immunoendocrine effects that result from them, can modulate myocardial tolerance to ischemia-reperfusion injury. The aim of this study was to investigate the effects of tetracycline (TTC) on myocardial infarct size in the isolated hearts obtained from obese rats with chemically-induced colitis (CIC). The association between TTC-induced changes in infarct size and intestinal microbiome composition as well as plasma levels of cytokines and short-chain fatty acids (SCFAs) was also studied.MethodsObesity was induced in Wistar rats by feeding them a high-fat, high-carbohydrate diet for five weeks. A single rectal administration of 3% acetic acid (2 mL) to the rats resulted in CIC. Healthy rats as well as obese rats with CIC received TTC (15 mg daily for 3 days) via gavage. The rats were euthanized, after which isolated heart perfusion with simulated global ischemia and reperfusion was performed. Infarct size was determined histochemically. Lipopolysaccharide (LPS) and cytokine levels in plasma were measured by enzyme-linked immunosorbent assay, whereas SCFA levels in plasma were measured by gas chromatography/mass spectrometry. The intestinal microbiome was analyzed using reverse transcription polymerase chain reaction.ResultsThe treatment with TTC resulted in significant infarct size limitation (50 ± 7 vs. 62 ± 4% for the control mice, p < 0.05) in the hearts from intact animals. However, infarct size was not different between the control rats and the obese rats with CIC. Furthermore, infarct size was significantly larger in TTC-treated obese rats with CIC than it was in the control animals (77 ± 5%, p < 0.05). The concentrations of proinflammatory cytokines and LPS in serum were elevated in the obese rats with CIC. Compared to the control rats, the rats with both obesity and CIC had lower counts of Lactobacillus and Bifidobacterium spp. but higher counts of Escherichia coli. The effects of TTC on infarct size were not associated with specific changes in SCFA levels.ConclusionsTTC reduced infarct size in the healthy rats. However, this effect was reversed in the obese animals with CIC. Additionally, it was associated with specific changes in gut microbiota and significantly elevated levels of cytokines and LPS.

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Section: Discussionmentioning

confidence: 82%

Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis

et al. 2019

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“…In a rat model of myocardial ischemia–reperfusion (I/R) injury, intravenous high-dose LPS administrated one hour before ischemia has been shown to impair myocardial function; however, low-dose LPS treatment did not affect myocardial function [ 41 ]. Moreover, low-dose LPS (50 ng/mL) treatment suppressed cardiomyocyte apoptosis and reduced myocardial infarction size in rat cardiomyocyte H9C2 cells [ 42 ].…”

Section: Therapeutic Efficacy Of Low-dose Lps-activated Cardiomyocyte...mentioning

confidence: 99%

Utility of In Vitro Cellular Models of Low-Dose Lipopolysaccharide in Elucidating the Mechanisms of Anti-Inflammatory and Wound-Healing-Promoting Effects of Lipopolysaccharide Administration In Vivo

Honda,

Inagawa

2023

IJMS

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Lipopolysaccharide (LPS) is a bacterial component that activates intracellular signaling pathways upon binding to the Toll-like receptor (TLR)-4/MD-2 complex. It is well known that LPS injected into animals and high-dose (100 ng/mL to 1 μg/mL) LPS treatment to innate immune cells induce an inflammatory response. In contrast, LPS is naturally present in the gastrointestinal tract, respiratory tract, and skin of humans and animals, and it has been shown that TLR-4-deficient animals cannot maintain their immune balance and gut homeostasis. LPS from commensal bacteria can help maintain homeostasis against mucosal stimulation in healthy individuals. Oral LPS administration has been shown to be effective in preventing allergic and lifestyle-related diseases. However, this effect was not observed after treatment with LPS at high doses. In mice, oral LPS administration resulted in the detection of LPS at a low concentration in the peritoneal fluid. Therefore, LPS administered at low and high doses have different effects. Moreover, the results of in vitro experiments using low-dose LPS may reflect the effects of oral LPS administration. This review summarizes the utility of in vitro models using cells stimulated with LPS at low concentrations (50 pg/mL to 50 ng/mL) in elucidating the mechanisms of oral LPS administration. Low-dose LPS administration has been demonstrated to suppress the upregulation of proinflammatory cytokines and promote wound healing, suggesting that LPS is a potential agent that can be used for the treatment and prevention of lifestyle-related diseases.

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“…Consequently, the pathogenesis of gut barrier injury and endotoxemia might differ. In addition, because LPS-induced cardiac dysfunction has been demonstrated to be dose-dependent in animal models [ 7 ], the extrapolation of one disease to another might not be straightforward.…”

Section: Introductionmentioning

confidence: 99%

Endotoxemia in Acute Heart Failure and Cardiogenic Shock: Evidence, Mechanisms and Therapeutic Options

Nguyen

Gautier

Masson

et al. 2023

JCM

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Acute heart failure and cardiogenic shock are frequently occurring and deadly conditions. In patients with those conditions, endotoxemia related to gut injury and gut barrier dysfunction is usually described as a driver of organ dysfunction. Because endotoxemia might reciprocally alter cardiac function, this phenomenon has been suggested as a potent vicious cycle that worsens organ perfusion and leading to adverse outcomes. Yet, evidence beyond this phenomenon might be overlooked, and mechanisms are not fully understood. Subsequently, even though therapeutics available to reduce endotoxin load, there are no indications to treat endotoxemia during acute heart failure and cardiogenic shock. In this review, we first explore the evidence regarding endotoxemia in acute heart failure and cardiogenic shock. Then, we describe the main treatments for endotoxemia in the acute setting, and we present the challenges that remain before personalized treatments against endotoxemia can be used in patients with acute heart failure and cardiogenic shock.

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The Effect of Lipopolysaccharide on Ischemic-Reperfusion Injury of Heart: A Double Hit Model of Myocardial Ischemia and Endotoxemia

Cited by 8 publications

References 25 publications

Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis

Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis

Utility of In Vitro Cellular Models of Low-Dose Lipopolysaccharide in Elucidating the Mechanisms of Anti-Inflammatory and Wound-Healing-Promoting Effects of Lipopolysaccharide Administration In Vivo

Endotoxemia in Acute Heart Failure and Cardiogenic Shock: Evidence, Mechanisms and Therapeutic Options

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