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.

Analysis of clinical characteristics and inpatient adverse events of elderly patients with Stanford A type of aortic dissection / 中国中西医结合急救杂志

Objective To illustrate the clinical characteristics of elderly patients with Stanford type A aortic dissection and to discuss the incidence of such inpatients' adverse events. Methods A retrospective study was conducted, 588 patients with definite diagnosis of Stanford type A aortic dissection admitted to Beijing Anzhen Hospital of Capital Medical University from January 2013 to December 2015 were enrolled, and they were divided into an elderly group (≥60 years, 79 cases) and a non-elderly group (< 60 years, 509 cases). The differences of general clinical data, results of hospitalization-related examinations, medication for treatment, surgical intervention and inpatient adverse events between the two groups were compared. Results Compared with non-elderly group, the proportion of male, age, stature, body mass index (BMI), proportion of alcohol history, hemoglobin (Hb), incidence of acute liver failure in hospital in elderly group were decreased significantly [proportion of male: 60.8% (48/79) vs. 80.6% (410/504), age (years):64.81±4.66 vs. 45.05±8.63, stature (cm): 169.41±8.09 vs. 173.39±7.59, BMI (kg/m2): 24.24±2.93 vs. 25.50±3.82, proportion of alcohol history: 12.7% (10/79) vs. 22.4% (114/509), Hb (g/L): 122.62±21.14 vs. 128.42±23.44, incidence of acute liver failure: 0 (0/79) vs. 5.3% (21/509), all P < 0.05], the proportion of diabetes history, proportion of cerebrovascular diseases, all-cause mortality in this hospital in elderly group were increased significantly [proportion of diabetes history: 24.1% (62/79) vs. 8.8% (45/509), proportion of cerebrovascular diseases: 6.3% (5/79) vs. 2.2% (11/509), all-cause mortality: 16.5% (13/79) vs. 7.1% (36/509), all P < 0.05], and the left ventricular end diastolic internal diameter (LVEDD) in elderly group decreased significantly (mm: 48.38±6.11 vs. 50.77±7.56, P <0.05). Conclusion The elderly patients with Stanford type A aortic dissection suffer from more complications and higher mortality, therefore, the risk consciousness should be strengthened for the senile patients and more attention should be paid on the prevention of the elderly inpatients' adverse events.

Relationship between acute kidney injury before thoracic endovascular aneurysm repair and in-hospital outcomes in patients with type B acute aortic dissection / 老年心脏病学杂志（英文版）

Objective Acute kidney injury (AKI) frequently occurs after catheter-based interventional procedures and increases mortality. How-ever, the implications of AKI before thoracic endovascular aneurysm repair (TEVAR) of type B acute aortic dissection (AAD) remain un-clear. This study evaluated the incidence, predictors, and in-hospital outcomes of AKI before TEVAR in patients with type B AAD. Meth-ods Between 2009 and 2013, 76 patients were retrospectively evaluated who received TEVAR for type B AAD within 36 h from symptom onset. The patients were classified into no-AKI vs. AKI groups, and the severity of AKI was further staged according to kidney disease:im-proving global outcomes criteria before TEVAR. Results The incidence of preoperative AKI was 36.8%. In-hospital complications was significantly higher in patients with preoperative AKI compared with no-AKI (50.0%vs. 4.2%, respectively;P<0.001), including acute renal failure (21.4%vs. 0, respectively;P<0.001), and they increased with severity of AKI (P<0.001). The maximum levels of body tem-perature and white blood cell count were significantly related to maximum serum creatinine level before TEVAR. Multivariate analysis showed that systolic blood pressure on admission (OR:1.023;95%CI:1.003–1.044;P=0.0238) and bilateral renal artery involvement (OR:19.076;95%CI:1.914–190.164;P=0.0120) were strong predictors of preoperative AKI. Conclusions Preoperative AKI frequently oc-curred in patients with type B AAD, and correlated with higher in-hospital complications and enhanced inflammatory reaction. Systolic blood pressure on admission and bilateral renal artery involvement were major risk factors for AKI before TEVAR.

Effects of basic fibroblast growth factor via coronary venous retroperfusion on bone marrow mesenchymal stem cell differentiation in vivo / 中国组织工程研究

BACKGROUND:In vitro studies have demonstrated that basic fibroblast growth factor (bFGF) promote the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cardiomyocyte-like cells. However, it is unclear whether coronary venous retroperfusion of bFGF stimulates BMSCs differentiation in vivo. OBJECTIVE:To evaluate the effects of coronary venous retroperfusion of bFGF on BMSCs differentiation in vivo. METHODS:BMSCs from 12 dogs were isolated by density gradient centrifugation and expanded in vitro. These cells were transfected by enhanced green fluorescence protein (EGFP) lentiviral vector and the transfection efficiency was analyzed. Acute myocardial infarction was induced by ligation of left anterior descending coronary artery. After 1 week, 10 survival animals were randomized to BMSCs group (n=5) and bFGF+BMSCs group (n=5). bFGF-and EGFP-positive BMSCs were reversely infused via coronary vein using over-the-wire bal oon catheter. One week after infusion, the number of EGFP-positive cells co-staining factor VIII and troponin I was compared between the two groups by immunofluorescence method. RESULTS AND CONCLUSION:BMSCs were successful y transfected by EGFP and the transfection efficiency was 85%. Immunofluorescence showed that EGFP-positive BMSCs were observed in 23.5%of slides. There were more EGFP-positive cells co-staining VIII and troponin I in the bFGF+BMSCs group than in the BMSCs group (P<0.05). Thus, the coronary venous retroperfusion of bFGF enhances the differentiation of BMSCs into vascular endothelial cells and cardiomyocytes. Combined delivery of bFGF and BMSCs can exert a synergistic effect to promote cardiac repair.