Early postoperative constrictive pericarditis in China: a single-center retrospective observational study.

Background: The diagnosis, treatment, and prognosis of early postoperative constrictive pericarditis (EPCP) have not been discussed in depth. The objective of this study was to devise and propose a management strategy for EPCP. Methods: In this study, constrictive pericarditis (CP) within 6 months after cardiac surgery was defined as EPCP, and patients were divided into two groups based on intraoperative findings: a parietal thickening group and a visceral thickening group. Results: A total of 20 patients were included in this study, and the incidence rate of recurrent pericardiectomy was 0.32% among all patients undergoing cardiovascular surgery. EPCP after valve surgery occurred in 85.0% of patients. Pleural effusion was the most common preoperative symptom, occurring in 90% of patients. Pericardial thickening occurred in the visceral layer in seven cases and in the parietal layer in 13 cases. There were no differences in comorbidities, C-reactive protein (CRP) level, or erythrocyte sedimentation rate (ESR) between the two groups. Most patients with visceral thickening (83.3%) needed cardiopulmonary bypass (CPB) assistance during surgery and had a longer hospital stay than those with parietal thickening (52.8±21.8 vs. 34.9±13.8 days, P=0.049). Central venous pressure (CVP) was decreased in all patients after pericardiectomy (24.9±6.96 vs. 8.9±2.92 cmH2O, P<0.001), and the cardiac function improved significantly in patients with parietal thickening [New York Heart Association (NYHA) grade ≥ III accounted for 28.6% of patients]. The long-term survival rate of patients with parietal thickening was 92.3% and that of patients with visceral thickening was 57.1%, and there was no significant difference between them (P=0.056). Conclusions: Recurrent episodes of chest tightness, pleural effusion, and elevated CVP within 6 months after cardiac surgery should be considered highly suggestive of EPCP. There are few points of difference between pericarditis with thickening of the parietal and visceral layers. After failure of conservative medical treatment, pericardiectomy results in significant improvements in cardiac function and quality of life, especially in patients with thickening of the parietal layer.

Experimental observation on a new chimney-shaped mechanical valve completely implanted above the mitral annulus in animals.

Current commercially available prosthetic valves suffer from limited size, high requirements for implantation technique, subvalvular structural destruction, and valve dysfunction due to proliferation of fibrous endothelial tissue. This study aims to perform the preclinical large animal experiments for surgically implanting a chimney-shaped artificial mechanical heart valve with zero left ventricular occupancy, which fully accommodates the movement of the valve leaflets in the valve frame and realizes completely supra-annular surgical implantation. A total of 7 sheep underwent the replacement of artificial valve, and 5 sheep survived normally until anatomical examination. The mechanical properties of these artificial mitral valves remain functionally normal. There was no obvious thromboembolism around the artificial valve and in the important organs. The tissue layer of suture ring was completely organized and endothelialized, and the thickness of tissue layer was about 0.6-1.0 mm. The follow-up of echocardiography showed that the left ventricular ejection fraction was normal (60-70%) before and 6 months after operation. The results of transvalvular pressure gradient and blood flow velocity of artificial valve were normal. Left ventricular retrograde angiography showed that the artificial valve was completely located in the left atrium with good position and normal opening and closing. There was no obvious perivalvular leakage and other abnormalities. At 3 and 6 months, there were no obvious abnormalities in blood routine test, liver and kidney function, and other indexes. The new chimney-shaped artificial mechanical valve implanted completely above the mitral annulus had good wear resistance, histocompatibility, and antithrombotic and hemodynamic performance.

Surgical Outcomes of Stent-Related Type A Dissection Compared with Spontaneous Type A Dissection.

OBJECTIVE: Aortic endovascular stent implantation includes thoracic endovascular aortic repair (TEVAR), hybrid aortic repair (HAR), and ascending aorta stent implantation (AASI). In this study, we compared the surgical outcomes of stent-related type A dissection (SRTAD) compared with spontaneous type A dissection (STAD). METHODS: From July 2011 to July 2014, we identified 17 SRTAD patients received surgical repair in our institution. Propensity score-matching was used to identify 34 STAD patients as controls. RESULTS: Preoperative data of SRTAD group and STAD group had no statistical difference. Selective cerebral perfusion (SCP) time was longer in SRTAD group than in STAD group (P <0.05). SRTAD group had a longer cross-clamp time compared with STAD group (P <0.05). No intraoperative deaths in two groups. No differences in CPB time and concomitant procedures between two groups. In-hospital mortality was 11.76% (2 of 17) in SRTAD group and 2.9% (1 of 34) in STAD group (P <0.05). No differences were found in intensive care unit (ICU) time, ventilation, paraparesis, and other postoperative complications between SRTAD and STAD groups. No difference was found in survival rate between SRTAD and STAD groups in the postoperative 1-year follow-up. CONCLUSIONS: SRTAD patients received surgical repair had a higher in-hospital mortality compared with STAD, but no differences were found in postoperative complications and mid-term outcomes.

Efficacy of cardiovascular surgery for Marfan syndrome patients: a single-center 15-year follow-up study.

BACKGROUND: Most Marfan syndrome (MFS) patients have thoracic aortic diseases which is the major cause of death. The aim of the study is to analyze the impact of different surgical procedures on prognosis of MFS patients. METHODS: We retrospectively analyzed the results of hospitalization and long-term follow-up of MFS patients who underwent surgical intervention in our center. RESULTS: Of the 135 MFS patients, 11 died during hospitalization (8.1%). There were no statistical differences in in-hospital mortality between the proximal surgery group and the distal surgery group (P=0.11). Compared to patients who underwent proximal aortic surgery, patients who underwent arch and distal surgery were more likely to have postoperative respiratory dysfunction (P=0.008). The type of surgical procedure was not associated with the incidence of complications during hospitalization. Pre-surgical New York Heart Association (NYHA) Functional Classification IV (P=0.047), EF <50% (P=0.047), pre-surgical atrial fibrillation (P=0.042), and the injury of dissection propagating onto coronary arteries (P=0.02) were independent risk factors for post-surgical mortality. After 15 years of follow-up, there were no deaths in the David group, while the 15-year survival rate for patients in the Bentall group was 73%±13.5%, and 71%±13.9% for patients in the arch surgery group (P=0.42). The probability of patients in the David group not requiring re-surgery after 15 years was 58.9%±20%, while it was 58.7%±12.1% for patients in the Bentall group, 71.5%±10.5% for patients in the Bentall + Arch group, and 12.5%±11.7% for patients in the Arch + Stent group (P=0.007). CONCLUSIONS: The David procedure was the most beneficial and had the highest long-term patient survival rates.

A practical strategy for immunofluorescent detecting multiple targets in mouse tissues without restrictions on the host specious resources of the primary antibodies.

Commercial deficiency of practical system to label multiple targets in experimental mouse tissues significantly hinders the feasibility to study the potential association between/among multiple targets using tissue-based immunofluorescence (IF) staining. We have developed a new protocol to do dual - labeling immunofluorescences on mouse tissues by combining direct and indirect immunofluorescence, making it possible to use commercial antibodies from the same specious (rabbit) to detect multiple targets in formalin-fixed paraffin-embedded (FFPE) archival mouse tissues simultaneously. This method applies indirect immunofluorescence to assess the first antigen in mouse tissues by using a rabbit anti-mouse polyclonal antibody and goat anti-rabbit antibody. After that, normal rabbit serum was employed to blocking the free binding sites of the previous antibodies. Direct immunofluorescence was used to assess the second antigen by a commercial kit-labeled rabbit anti-human (mouse) antibody at different emission wavelength. At last, cell nuclei were co-stained by DAPI. The outcomes demonstrated that this protocol obtain promising signals of both antigens and the nuclei. Moreover, this method also works on infection disease models in which samples are often over fixed due to biosafety rules.

Exchange protein directly activated by cAMP plays a critical role in regulation of vascular fibrinolysis.

Plasmin-mediated fibrinolysis at the surface of vascular endothelial cells (SVEC) plays a key role in maintaining vascular hemostasis, in which the cAMP pathway participates. After externalization to the SVEC, annexin A2 (ANXA2) serves as a platform for conversion of plasminogen to plasmin. Here we describe a regulatory role of the exchange protein directly activated by cAMP (EPAC) in ANXA2 externalization and vascular fibrinolysis. Knockout of EPAC1 in mice results in a decreased ANXA2 expression on the SVEC associated with increased fibrin deposition and fibrinolytic dysfunction. Reduced levels of EPAC1 are also found in endocardial tissues beneath atrial mural thrombi in patients. Notably, administration of recombinant ANXA2 ameliorates fibrinolytic dysfunction in the EPAC1-null mice. Mechanistically, EPAC1 regulates the SVEC plasminogen conversion depended on ANXA2. EPAC1 promotes tyrosine-23 phosphorylation of ANXA2, a prerequisite for its recruitment to the SVEC. Our data thus reveal a novel regulatory role for EPAC1 in vascular fibrinolysis.

Exchange Protein Directly Activated by cAMP Modulates Ebola Virus Uptake into Vascular Endothelial Cells.

Members of the family Filoviridae, including Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic fever in humans and nonhuman primates. Given their high lethality, a comprehensive understanding of filoviral pathogenesis is urgently needed. In the present studies, we revealed that the exchange protein directly activated by cAMP 1 (EPAC1) gene deletion protects vasculature in ex vivo explants from EBOV infection. Importantly, pharmacological inhibition of EPAC1 using EPAC-specific inhibitors (ESIs) mimicked the EPAC1 knockout phenotype in the ex vivo model. ESI treatment dramatically decreased EBOV infectivity in both ex vivo vasculature and in vitro vascular endothelial cells (ECs). Furthermore, postexposure protection of ECs against EBOV infection was conferred using ESIs. Protective efficacy of ESIs in ECs was observed also in MARV infection. Additional studies using a vesicular stomatitis virus pseudotype that expresses EBOV glycoprotein (EGP-VSV) confirmed that ESIs reduced infection in ECs. Ultrastructural studies suggested that ESIs blocked EGP-VSV internalization via inhibition of macropinocytosis. The inactivation of EPAC1 affects the early stage of viral entry after viral binding to the cell surface, but before early endosome formation, in a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-dependent manner. Our study delineated a new critical role of EPAC1 during EBOV uptake into ECs.

MicroRNA-124 controls human vascular smooth muscle cell phenotypic switch via Sp1.

Phenotypic switch of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of atherosclerosis and aortic dissection. However, the mechanisms of phenotypic modulation are still unclear. MicroRNAs have emerged as important regulators of VSMC function. We recently found that microRNA-124 (miR-124) was downregulated in proliferative vascular diseases that were characterized by a VSMC phenotypic switch. Therefore, we speculated that the aberrant expression of miR-124 might play a critical role in human aortic VSMC phenotypic switch. Using quantitative RT-PCR, we found that miR-124 was dramatically downregulated in the aortic media of clinical specimens of the dissected aorta and correlated with molecular markers of the contractile VSMC phenotype. Overexpression of miR-124 by mimicking transfection significantly attenuated platelet-derived growth factor-BB-induced human aortic VSMC proliferation and phenotypic switch. Furthermore, we identified specificity protein 1 (Sp1) as the downstream target of miR-124. A luciferase reporter assay was used to confirm direct miR-124 targeting of the 3'-untranslated region of the Sp1 gene and repression of Sp1 expression in human aortic VSMCs. Furthermore, constitutively active Sp1 in miR-124-overexpressing VSMCs reversed the antiproliferative effects of miR-124. These results demonstrated a novel mechanism of miR-124 modulation of VSMC phenotypic switch by targeting Sp1 expression.NEW & NOTEWORTHY Previous studies have demonstrated that miR-124 is involved in the proliferation of a variety of cell types. However, miRNAs are expressed in a tissue-specific manner. We first identified miR-124 as a critical regulator in human aortic vascular smooth muscle cell differentiation, proliferation, and phenotype switch by targeting the 3'-untranslated region of specificity protein 1.