Off-pump epicardial ventricular reconstruction restores left ventricular twist and reverses remodeling in an ovine anteroapical aneurysm model

ObjectiveThe loss of normal apical rotation is associated with left ventricular (LV) remodeling and systolic dysfunction in patients with congestive heart failure after myocardial infarction. The objective of the present study was to evaluate the effect of epicardial ventricular reconstruction, an off-pump, less-invasive surgical reshaping technique, on myocardial strain, LV twist, and the potential alteration of myocardial fiber orientation in an ovine model of LV anteroapical aneurysm.MethodsLV anteroapical myocardial infarction was induced by coil embolization of the left anterior descending artery. Eight weeks after occlusion, epicardial ventricular reconstruction was performed using left thoracotomy under fluoroscopic guidance in 8 sheep to completely exclude the scar. The peak systolic longitudinal/circumferential strains and LV twist were evaluated using speckle tracking echocardiography before (baseline), after device implantation, and at 6 weeks of follow-up.ResultsEpicardial ventricular reconstruction was completed in all sheep without any complications. Immediately after device implantation, LV twist significantly increased (4.18 ± 1.40 vs baseline 1.97 ± 1.92; P = .02). The ejection fraction had increased 17% and LV end-systolic volume had decreased 40%. The global longitudinal strain increased from −5.3% to −9.1% (P < .05). Circumferential strain increased in both middle and apical LV segments, with the greatest improvement in the inferior lateral wall (from −11.4% to −20.6%, P < .001). These effects were maintained ≥6 weeks after device implantation without redilation.ConclusionsLess invasive than alternative therapies, epicardial ventricular reconstruction on the off-pump beating heart can restore LV twist and systolic strain and reverse LV remodeling in an ovine anteroapical aneurysm model

Low molecular weight heparin in surgical valve procedures: When and how much for an optimal prophylaxis?

Background: Periprocedural antithrombotic prophylaxis in patients undergoing surgical valve procedures (SVP) is insufficiently investigated. Low molecular weight heparin (LMWH) has been considered as an alternative to unfractionated heparin (UFH). However, safety and efficacy of this prophylaxis strategy is unknown. This study aimed to investigate safety and efficacy of periprocedural LMWH prophylaxis and determine optimal dosage and timing for periprocedural cessation and initiation.Methods: The present study is a retrospective, single-center observational analysis of 388 patients who underwent SVP (valve replacement or valvuloplasty) between 2015 and 2016. In-hospital endpoints were bleeding, transfusions, reoperation due to bleeding, and thromboembolic events. Results: Giving the first dose of LMWH on the day of SVP was a risk factor for bleeding (OR 1.07; 95% CI 1.04–1.10; p &lt; 0.001), transfusions (OR 1.04; 95% CI 1.01–1.07; p = 0.008) and reoperation due to bleeding (OR 1.20; 95% CI 1.12–1.28; p &lt; 0.001), with &gt; 40 mg/day as a predictor. A higher dosage of LMWH premedication was an independent risk factor for bleeding (OR 1.02; 95% CI 1.00–1.04; p = 0.03) and transfusion (OR 1.03; 95% CI 1.01–1.05; p = 0.01), with &gt; 60 mg/day as a predictor for these events. LMWH dosed within 24 h prior to SVP increased the risk of transfusion (AUC 0.636; 95% CI 0.496–0.762; p = 0.04).Conclusions: Bleeding is an important early concern after surgical valve procedures. Safety and efficacy of periprocedural prophylaxis with LMWH depends on dosage and the timing of its administration. The most optimal periprocedural prophylaxis in the SVP population appears to be LMWH in dosage of 40–60 mg/day, which is recommended for deep vein thrombosis prophylaxis, ceased at least one day before SV

Oral Neutrophil Transcriptome Changes Result in a Pro-Survival Phenotype in Periodontal Diseases

<div><p>Background</p><p>Periodontal diseases are inflammatory processes that occur following the influx of neutrophils into the periodontal tissues in response to the subgingival bacterial biofilm. Current literature suggests that while neutrophils are protective and prevent bacterial infections, they also appear to contribute to damage of the periodontal tissues. In the present study we compare the gene expression profile changes in neutrophils as they migrate from the circulation into the oral tissues in patients with chronic periodontits and matched healthy subjects. We hypothesized that oral neutrophils in periodontal disease patients will display a disease specific transcriptome that differs from the oral neutrophil of healthy subjects.</p><p>Methods</p><p>Venous blood and oral rinse samples were obtained from healthy subjects and chronic periodontitis patients for neutrophil isolation. mRNA was isolated from the neutrophils, and gene expression microarray analysis was completed. Results were confirmed for specific genes of interest by qRT-PCR and Western Blot analysis.</p><p>Results and Discussion</p><p>Chronic periodontitis patients presented with increased recruitment of neutrophils to the oral cavity. Gene expression analysis revealed differences in the expression levels of genes from several biological pathways. Using hierarchical clustering analysis, we found that the apoptosis network was significantly altered in patients with chronic inflammation in the oral cavity, with up-regulation of pro-survival members of the Bcl-2 family and down-regulation of pro-apoptosis members in the same compartment. Additional functional analysis confirmed that the percentages of viable neutrophils are significantly increased in the oral cavity of chronic periodontitis patients.</p><p>Conclusions</p><p>Oral neutrophils from patients with periodontal disease displayed an altered transcriptome following migration into the oral tissues. This resulted in a pro-survival neutrophil phenotype in chronic periodontitis patients when compared with healthy subjects, resulting in a longer-lived neutrophil. This is likely to impact the severity and length of the inflammatory response in this oral disease.</p></div

Oral chronic inflammation increases neutrophil recruitment to the site of infection.

<p>The proportion of neutrophils recruited to the oral cavity was counted in healthy patients, patients with chronic periodontits. * p ≤ 0.02; vs. Healthy. All data are mean ± SEM. Healthy subjects (n = 14); Generalized Periodontitis (n = 62).</p

Demographics and clinical parameters of study subjects.

<p>ns - not significant;</p>*<p>p-value ≤0.05 vs. Healthy subjects.</p

Graphic representation of Death Receptor Pathway and Apoptosis Signaling Pathway in neutrophils demonstrates that they are altered in neutrophils in chronic inflammation.

<p>IPA canonical pathway analysis of Death Receptor Signaling Pathway in neutrophils from (A) healthy individuals and (B) chronic periodontitis patients. Red represents up-regulated genes, green are down-regulated genes and white symbols depict neighbouring genes in this analysis.</p

DAVID pathway analysis – Common pathways of Chronic Periodontitis and Healthy Subjects.

<p>Additional analysis can be found in File S3.</p

Functional confirmation of microarray data with Western Blotting and by Flow Cytometry – Presenting up-regulation of anti-apoptosis and down-regulation of pro-apoptosis proteins.

<p>(A) Western blotting quantification; 15 µg of protein from total cell lysate of PMN-B and PMN-O from chronic periodontitis patients were loaded, expression was normalized to β-actin used as internal control (n = 4). (B) Representative Western Blot of members of apoptosis pathway Bcl-xl (anti-apoptosis), Bim and Bax (pro-apoptosis). (C) Summary of relative changes in BCL-2 family (Ratio of expression in PMN-O compared to PMN-B). (D) Percentages of viable cells were analyzed by Flow cytometry in oral neutrophils (n = 3). Cells that were negative for Annexin V and PI were considered viable. * p ≤ 0.05 vs. Healthy. All data are mean ± SEM from 3 independent experiments.</p

Multi analysis of Gene Ontology (GO) annotations demonstrates that some key functions are preserved during inflammatory process in the mouth.

<p>The GO terms grouped into Cellular Components that are uniquely enriched in healthy patients (green) and chronic periodontits patients (red). Significantly enriched GO terms in both comparisons are marked yellow. The degree of color saturation of each node is positively correlated with the significance of enrichment of the corresponding GO term. Red arrows stand for relationship between two enriched GO terms, black solid arrows stand for relationship between enriched and unenriched terms.</p

Validation of microarray data with qRT-PCR.

<p>(A) Quantitative real time PCR was used to quantify gene expression of selected genes from neutrophils isolates from blood and oral rinse. Results are expressed as fold vs. Blood expression used as internal control. Gene expression was normalized with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a reference gene. (B) Correspondence between mean fold change (FC) values obtained by microarray (X) vs. qRT-PCR (y) analysis. The diagonal line represents the ideal correspondence trend (Pearson correlation r = 0.8712, p-value ≤0.01). All data are mean ± SEM from 3 independent experiments (n = 4).</p