Gastrin attenuates sepsis-induced myocardial dysfunction by down-regulation of TLR4 expression in macrophages

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Meta analysis of the relationship between sepsis-induced myocardial dysfunction and hypertension / 中国医师杂志

Objective:To systematically review the relationship between the sepsis-induced myocardial dysfunction and hypertension.Methods:PubMed, Embase, Cochrane Library, China National Knowledge Internet (CNKI), China Biology Medicine (CBM) and Wanfang were searched both with Chinese and English keywords from the establishment of the database to January 2022 on the correlation between sepsis-induced myocardial dysfunction and hypertension. Newcastle-Ottawa Quality Assessment Scale (NOS) was used to evaluate the literature quality, and Stata 12.0 software was used to perform meta-analysis on the included literature.Results:After screening, 16 literatures were included, a total of 3 758 subjects was involved. Meta-analysis results showed that patients with hypertension had a higher incidence of sepsis-induced myocardial dysfunction, and the results were statistically significant. Subgroup analysis and sensitivity analysis suggested stable results.Conclusions:Hypertension is a risk factor for sepsis-induced myocardial dysfunction, and the results are statistically significant. Early intervention may improve the prognosis of septic patients.

Advances in animal models of sepsis-induced myocardial dysfunction / 中华危重病急救医学

Sepsis-induced myocardial dysfunction (SIMD) has a high morbidity and mortality, and seriously threatens human health. However, the pathogenesis of the SIMD is still unclear. The previous studies have showed that the SIMD can adversely affect cardiac function through a variety of direct or indirect mechanism, such as autonomic nervous system function damage, pro-inflammatory mediators and activated immune cells induced cardiomyopathy. There is no uniform diagnostic criteria and treatment options. A stable and reliable animal model plays important role in the study that determine the pathogenesis, pathophysiological processes and treatment of SIMD. At present, there are many animal models of cardiac dysfunction caused by sepsis, unfortunately there is no stable, reliable and specific animal model at present. Therefore, it is important to construct a stable and reliable model for studying SIMD. The unified standard of cardiac dysfunction is conducive to the integration and further research. This review focused on pathogenesis of SIMD, routine ways of animal model of SIMD, observation index and basic research to provide references for the researcher to choose the proper animal model.

Clinical Efficacy of Yang Warming, Stasis Dissipating and Detoxifying Method on Sepsis-induced Myocardial Dysfunction / 中国实验方剂学杂志

Objective:To observe clinical efficacy of Shengma Biejia Tang combined with Shenfutang on sepsis-induced myocardial dysfunction (SIMD) and study the controlling effect on inflammatory reaction. Method:Eighty-eight patients with SIMD were randomly divided into control group (44 cases) and observation group (44 cases) by random number table. Patients in control group received the early bundle therapy of sepsis, including fluid resuscitation, anti-infection treatment and vasoactive drugs. In addition to the therapy of control group, patients in observation were also given Shengma Biejia Tang combined with Shenfutang, 1 dose/day. And a course of treatment was 7 days. Before and after treatment, levels of troponin (cTnI), creatine kinase isoenzyme (CK-MB), N terminal brain natriuretic precursor (NT-proBNP), calcitonin (PCT), hypersensitivity C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukins-6 (IL-6) and blood lactic acid (LAC) were detected. And color Doppler ultrasound examination of the heart was performed to record left ventricular ejection fraction (LVEF), blood flow velocity of early mitral valve diastole and ratio of blood flow velocity at atrial systolic peak (E/A) and stroke volume (SV). And lactate clearance rate (LCR) was calculated. And sequential (sepsis-related) organ failure assessment (SOFA), acute physiology and chronic health (APACHEⅡ) and traditional Chinese medicine(TCM)syndromes were scored. Result:After treatment, levels of cTnI, NT-ProBNP, CK-MB, Hs-CRP, IL-6, PCT, TNF-α and LAC in observation group were lower than those in control group (PPPConclusion:In addition to the integrated western medicine, Shengma Biejia Tang combined with Shenfutang can control inflammatory reaction, relieve myocardial inhibition and myocardial damage, and protect and improve heart function, and alleviate the symptoms.