Role of Jagged1-Hey1 Signal in Angiotensin II-induced Impairment of Myocardial Angiogenesis.

BACKGROUND: Angiotensin II (Ang II) is a major contributor to the development of heart failure. However, the molecular and cellular mechanisms that underlie this process remain elusive. Inadequate angiogenesis in the myocardium leads to a transition from cardiac hypertrophy to dysfunction, and our previous study showed that Ang II significantly impaired the angiogenesis response. The current study was designed to examine the role of Jagged1-Notch signaling in the effect of Ang II during impaired angiogenesis and cardiac hypertrophy. METHODS: Ang II was subcutaneously infused into 8-week-old male C57BL/6 mice at a dose of 200 ng·kg-1·min-1 for 2 weeks using Alzet micro-osmotic pumps. N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester (DAPT), a γ-secretase inhibitor, was injected subcutaneously during Ang II infusion at a dose of 10.0 mg·kg-1·d-1. Forty mice were divided into four groups (n = 10 per group): control group; Ang II group, treated with Ang II; DAPT group, treated with DAPT; and Ang II + DAPT group, treated with both Ang II and DAPT. At the end of experiments, myocardial (left ventricle [LV]) tissue from each experimental group was evaluated using immunohistochemistry, Western blotting, and real-time polymerase chain reaction. Data were analyzed using one-way analysis of variance test followed by the least significant difference method or independent samples t-test. RESULTS: Ang II treatment significantly induced cardiac hypertrophy and impaired the angiogenesis response compared to controls, as shown by hematoxylin and eosin (HE) staining and immunohistochemistry for CD31, a vascular marker (P < 0.05 for both). Meanwhile, Jagged1 protein was significantly increased, but gene expression for both Jag1 and Hey1 was decreased in the LV following Ang II treatment, compared to that in controls (relative ratio for Jag1 gene: 0.45 ± 0.13 vs. 0.84 ± 0.15; relative ratio for Hey1 gene: 0.51 ± 0.08 vs. 0.91 ± 0.09; P < 0.05). All these cellular and molecular effects induced by Ang II in the hearts of mice were reduced by DAPT treatment. Interestingly, Ang II stimulated Hey1, a known Notch target, but did not affect the expression of Hey2, another Notch target gene. CONCLUSIONS: A Jagged1-Hey1 signal might mediate the impairment of angiogenesis induced by Ang II during cardiac hypertrophy.

Independent risk factors for hypoxemia after surgery for acute aortic dissection.

OBJECTIVES: To determine risk factors associated with postoperative hypoxemia after surgery for acute type A aortic dissection. METHODS: We retrospectively analyzed the clinical data of 192 patients with acute type A aortic dissection who underwent surgery in Qingdao Municipal Hospital, Medical College of Qingdao University, Qingdao, China between January 2007 and December 2013. Patients were divided into hypoxemia group (n=55) [arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 200 mm Hg] and non-hypoxemia group (n=137) [PaO2/FiO2 > 200 mm Hg]. Perioperative clinical data were analyzed and compared between the 2 groups. RESULTS: The incidence of postoperative hypoxemia after surgery for acute aortic dissection was 28.6% (55/192). Perioperative death occurred in 13 patients (6.8%). Multivariate regression identified body mass index (BMI) > 25 kg/m2 (OR=21.929, p=0.000), deep hypothermic circulatory arrest (DHCA) (OR=11.551, p=0.000), preoperative PaO2/FiO2 ≤ 300 mm Hg (OR=7.830, p=0.000) and blood transfusion > 6U in 24 hours postoperatively (OR=12.037, p=0.000) as independent predictors of postoperative hypoxemia for patients undergoing Stanford A aortic dissection surgery. CONCLUSION: Our study demonstrated that BMI > 25 kg/m2, DHCA, preoperative PaO2/FiO2 ≤ 300 mm Hg, and blood transfusion in 24 hours postoperatively > 6U were independent risk factors of the hypoxemia after acute type A aortic dissection aneurysm surgery.

Independent risk factors for ventilator-associated pneumonia after cardiac surgery.

OBJECTIVE: To investigate the related factors and pathogens of ventilator-associated pneumonia (VAP) after heart surgery so as to provide evidences for clinical prevention and therapy. METHODS: In total 1,688 cases were collected from January 2004 to January 2011. Overall 105 patients developed VAP. Retrospectively analyzed these patients after heart surgery to determine the clinical data, pathogens and treatment measures. RESULTS: The frequency of ventilator-associated pneumonia was 6.2% (105/1 688), and mortality was 25.7% (27/105), 198 pathogen strains were isolated by bacterial culture, in which Gram negative bacteria accounted for 69.2% (137/198), Gram positive bacteria 27.8% (55/198), and fungi 3.0% (6/198). The independent risk factors for VAP after cardiac surgery were: age >70 (p < .01), emergent surgery (p < .01), perioperative blood transfusions (p < 0.01), reintubation (p < .01) and days of mechanical ventilation (MV) (p < .01). Median length of stay in the ICU for patients who developed VAP or not was, respectively, (24.7 ± 4.5) days versus (3.2 ± 1.5) days (p < .05), and mortality was, respectively, 25.7% versus 2.9% in both populations (p < .05). CONCLUSION: Age >70, emergent surgery, perioperative blood transfusions, reintubation and days of MV are the risk factors for VAP in patients following cardiac surgery. P. aeruginosa, P. klebsiella, S. aureus, and Acinetobacter baumannii were the main pathogens of VAP. According to the cause of VAP, active prevention and treatment measures should be developed and applied to shorten the time of MV and improve chances of survival.

Perioperative levosimendan therapy is associated with a lower incidence of acute kidney injury after cardiac surgery: a meta-analysis.

OBJECTIVE: Levosimendan is a calcium sensitizer that enhances myocardial contractility without increasing myocardial oxygen use. Limited data are available on its renal-protective effect, and no statistically significant effects have been found. A meta-analysis was conducted for randomized studies to show whether perioperative levosimendan use could reduce acute kidney injury (AKI) in patients undergoing cardiac surgery. DATA SOURCES: BioMed Central, PubMed EMBASE, and the Cochrane Central Register of Controlled Trials were searched for pertinent studies. STUDY SELECTION: Randomized trials that compared levosimendan versus placebo or any other control in cardiac surgery with data on AKI were included. Exclusion criteria were duplicate publications, nonadult studies, oral administration of levosimendan, and studies with no data on AKI. DATA EXTRACTION: Study endpoints, study design, population, clinical setting, levosimendan dosage, and treatment duration were extracted. DATA SYNTHESIS: Data from 529 patients in 5 randomized trials were analyzed. The analysis showed that levosimendan decreased postoperative incidence of AKI in the levosimendan group. CONCLUSIONS: This analysis suggests that levosimendan might reduce renal injury in adult patients undergoing cardiac surgery. More prospective randomized studies are needed to further demonstrate the benefits of levosimendan on renal protection in cardiac surgery.

[Clinical analysis of 105 cases of ventilator-associated pneumonia after heart surgery].

OBJECTIVE: To investigate the related factors and pathogens of ventilator-associated pneumonia (VAP) after heart surgery. METHODS: VAP was diagnosed in 105 patients out of 1688 cases (6.2%) who underwent heart surgery in our department between January 2004 and January 2011. Clinical data, pathogens and treatments were analyzed. RESULTS: Incidence of VAP was 6.2% (105/1688), and 53.0% (105/198) in patients who required more than 48 hours of mechanical ventilation. One hundred and ninety-eight pathogen strains were isolated by bacterial culture, in which Gram negative bacteria accounted for 69.2% (137/198), Gram positive bacteria 27.8% (55/198), and fungi for 3.0% (6/198). Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus were the main pathogens of VAP. The independent risk factors for VAP were: age > 70 years, emergent surgery, perioperative transfusions, reintubation and days of mechanical ventilation (all P < 0.01). Median length of stay in the ICU for patients who developed VAP or not was (24.7 ± 4.5) days versus (3.2 ± 1.5) days, respectively (P < 0.05) and in-hospital mortality was 25.7% (27/105) versus 2.9% (46/1583) respectively (P < 0.05). CONCLUSIONS: Patients undergoing heart surgery have a high frequency of developing VAP, especially in patients that require more than 48 hours of mechanical ventilation. VAP is associated with high in-hospital mortality. Age > 70 years, emergent surgery, perioperative transfusions, reintubation and prolonged mechanical ventilation use are independent risk factors for VAP in patients following cardiac surgery. Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus are the main pathogens of VAP.