Sepsis is one of the most common causes of mortality in intensive care units. Although sepsis-associated encephalopathy (SAE) is reported to be a leading manifestation of sepsis, its pathogenesis remains to be elucidated. In this study, we investigated whether exogenous recombinant human erythropoietin (rhEPO) could protect brain from neuronal apoptosis in the model of SAE. We showed that application of rhEPO enhanced Bcl-2, decreased Bad in lipopolysaccharide treated neuronal cultures, and improved neuronal apoptosis in hippocampus of cecal ligation and peroration rats. We also found that rhEPO increased the expression of phosphorylated AKT, and the antiapoptotic role of rhEPO could be abolished by phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002 or SH-5. In addition, systemic sepsis inhibited the hippocampal-phosphorylated mammalian target of rapamycin (mTOR) and p70S6K (downstream substrates of PKB/AKT signaling), which were restored by administration of exogenous rhEPO. Moreover, treatment with mTOR-signaling inhibitor rapamycin or transfection of mTOR siRNA reversed the neuronal protective effects of rhEPO. Finally, exogenous rhEPO rescued the emotional and spatial cognitive defects without any influence on locomotive activity. These results illustrated that exogenous rhEPO improves brain dysfunction by reducing neuronal apoptosis, and AKT/mTOR signaling is likely to be involved in this process. Application of rhEPO may serve as a potential therapy for the treatment of SAE.

Cx43 level was upregulated in LV myocardium of SHR during early stage of hypertrophy. Angiotensin II type 1 receptor antagonist losartan prevented Cx43 gap junction remodeling in hypertrophied left ventricles, possibly through the NF-kappaB pathway.

The present study explored the effect of ghrelin in protecting neurons from apoptosis in sepsis-associated encephalopathy. Ghrelin (100 nM) increased the cell viability treated with lipopolysaccharide (1.0 μg/ml, 24 h). The expression of p-Akt and Bcl-2 were decreased and caspase-3 increased both in lipopolysaccharide-treated primary hippocampal cultures and in the cecal ligation and perforation model, which were alleviated in the presence of ghrelin. In vitro, the protecting effect of ghrelin was almost abolished by the Akt inhibitor, SH-5. In vivo, the cecal ligation and perforation rats exhibited emotional, learning, and memory deficits. Administration of ghrelin attenuated the cognitive deficits significantly. These results indicate that ghrelin alleviates neuronal apoptosis and subsequent cognitive impairments in sepsis-associated encephalopathy through the Akt pathway.

A 44-year-old hypertensive male was admitted with a type A aortic dissection originating just above the aortic valve and involving the innominate, left subclavian, left renal, and bilateral iliac arteries. The celiac, superior mesenteric, and splenic arteries were not involved in the dissection. An echocardiogram revealed an aortic root diameter of 4.7 cm with moderate aortic insufficiency due to aortic valve prolapse. At the time of surgery, cardiopulmonary bypass was established with right axillary artery and right atrial cannulation. The aortic root and ascending aorta were replaced with a #25 Carbomedics composite conduit (Sorin Group Italia S.R.L., Milan, Italy). The aortic specimen showed no evidence of any connective tissue disease. During the postoperative period, the patient developed acute renal failure which required institution of continuous renal replacement therapy. On the 10th postoperative day, the patient became hypotensive and developed midepigastric pain, hematemesis, and bloody stools. His hematocrit decreased from 12.2 to 4.5 g/dL and his international normalized ratio was 2.3. Coumadin was discontinued and vitamin K and fresh frozen plasma were administered. He continued to have hematemesis and gastroscopy showed active bleeding from a 3.5 × 4.0 cm mass in the posterior wall of the gastric fundus (Figure 1). An abdominal computed tomography scan showed no gastric mass, but instead, revealed an enlarged spleen (135.47 × 43.49 × 110 mm 3 postop vs 98.38 × 33.92 × 93.50 mm 3 preop), with the upper pole compressing the posterior wall of the gastric fundus creating a mass-like effect (Figure 2). These findings were confirmed at the time of laparotomy and a splenectomy and partial gastrectomy was performed. FIGURE 1The gastroscopy showed the mass was at the posterior wall of the fundus, 3.5 cm × 4 cm. There was extravasated blood surrounding the mass J Card Surg. 2018;33:853-854.wileyonlinelibrary.com/journal/jocsThe pathology showed no evidence of any gastric tumor or splenic emboli or ischemic changes other than congestion. The splenic artery had no evidence of dissection. The patient tolerated the procedure well and was subsequently discharged on coumadin without any further hematemesis.