Experimental diabetes increases production of reactive oxygen-nitrogen species and inhibits astrocytic gap junctional communication in tissue culture and brain slices from streptozotocin (STZ)-diabetic rats by unidentified mechanisms. Relative connexin (Cx) protein levels were assessed by Western blotting using extracts from cultured astrocytes grown in high (25 mmol/L) or low (5.5 mmol/L) glucose for 2–3 weeks and STZ-diabetic rat brain. Chemiluminescent signals for diabetic samples were normalized to those of controls on the same blot and same protein load. Growth in high glucose did not alter relative Cx26 level, whereas Cx30 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were reduced by ~30% and Cx43 increased ~1.9-fold. In the inferior colliculus of STZ-diabetic rats, Cx30 and Cx43 levels in three of four rats were half those of controls, whereas GAPDH and actin were unaffected. Diabetes did not affect levels of Cx30, Cx43, and GAPDH in cerebral cortex, but actin level rose 24%. Cx43 was predominantly phosphorylated in control and diabetic samples, so reduced dye transfer is not due to overall dephosphorylation of Cx43. Astrocytic growth in high glucose reduced dye-labeled area by 75%, but 10 min treatment with dithiothreitol restored normal dye transfer. In contrast, nitric oxide donors inhibited dye transfer among astrocytes grown in low glucose by 50–65% within 1h. Thus, modifications arising from oxidative-nitrosative stress, not altered connexin levels, may underlie reduced dye transfer among severely-hyperglycemic cultured astrocytes, whereas both oxidative-nitrosative stress and regionally-selective down-regulation of connexin protein content may affect gap junctional communication in brain of STZ-diabetic rats.
BackgroundPosterior pericardiotomy (PP) has been shown to reduce the incidence of pericardial effusion and postoperative atrial fibrillation (POAF) after cardiac surgery. However, the procedure and the totality of its effects are poorly known in the cardiac surgery community. We performed a study-level meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of PP in cardiac surgery patients.MethodsA systematic literature search was conducted on three medical databases (Ovid MEDLINE, Ovid Embase, Cochrane Library) to identify RCTs reporting outcomes of patients that received a PP or no intervention after cardiac surgery. The primary outcome was the incidence of POAF. Key secondary outcomes were operative mortality, incidence of pericardial and pleural effusion, cardiac tamponade, length of stay (LOS), pulmonary complications, amount of chest drainage, need for intra-aortic balloon pump, and re-exploration for bleeding.ResultsEighteen RCTs totaling 3,531 patients were included. PP was associated with a significantly lower incidence of POAF (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.32–0.64, P < 0.0001), early (OR 0.18, 95% CI 0.10–0.34, P < 0.0001) and late pericardial effusion (incidence rate ratio 0.13, 95% CI 0.06–0.29, P < 0.0001), and cardiac tamponade (risk difference −0.02, 95% CI −0.04 to −0.01, P = 0.001). PP was associated with a higher incidence of pleural effusion (OR 1.42, 95% CI 1.06–1.90, P = 0.02), but not pulmonary complications (OR 0.82, 95% CI 0.56–1.19; P = 0.38). No differences in other outcomes, including operative mortality, were found.ConclusionsPP is a safe and effective intervention that significantly decreases the incidence of POAF and pericardial effusion following cardiac surgery.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=261485, identifier: CRD42021261485.
Coronary artery bypass grafting (CABG) is the most frequently performed cardiac surgery worldwide. The reported incidence of graft failure ranges between 10% and 50%, depending upon the type of conduit used. Thrombosis is the predominant mechanism of early graft failure, occurring in both arterial and vein grafts. Significant advances have been made in the field of antithrombotic therapy since the introduction of aspirin, which is regarded as the cornerstone of antithrombotic therapy for prevention of graft thrombosis. Convincing evidence now exists that dual antiplatelet therapy (DAPT), consisting of aspirin and a potent oral P2Y12 inhibitor, effectively reduces the incidence of graft failure. However, this is achieved at the expense of an increase in clinically important bleeding, underscoring the importance of balancing thrombotic risk and bleeding risk when considering antithrombotic therapy after CABG. In contrast, anticoagulant therapy has proved ineffective at reducing the occurrence of graft thrombosis, pointing to platelet aggregation as the key driver of graft thrombosis. We provide a comprehensive review of current practice for prevention of graft thrombosis and discuss potential future concepts for antithrombotic therapy including P2Y12 inhibitor monotherapy and short-term DAPT.
Objective: To assess follow-up mortality and reoperation rate in patients undergoing Bentall-De Bono operation according to the type of composite valve graft used. Methods: All consecutive adult patients operated on between May 1997 and December 2019 at our institution were included in the analysis and classified according to the use of a biological or a mechanical composite valve graft (bCVG or mCVG). The primary outcomes were follow-up mortality and reoperation rate. Secondary outcomes were operative mortality and major adverse events (MAEs) including operative mortality, myocardial infarction, cerebrovascular accident, dialysis, tracheostomy, and re-exploration for bleeding. Kaplan-Meier and competing risk analyses were used. Propensity matching analysis was used to balance differences in baseline characteristics between procedures. Results: Of 1,210 included patients, 798 received a bCVG and 412 a mCVG. The mean follow-up was 6.64 ± 0.21 years. The ten-year mortality rate was higher in the mCVG group (25.3% vs. 16.4%, P = 0.023). The ten-year reoperation rate was higher in the bCVG group (7.4% vs. 1.1%, P < 0.001). Overall operative mortality was 0.7%, and MAEs occurred in 6.2% of patients, with no significant differences between groups. Older age (hazard ratio [HR] 1.06, 95% confidence interval [CI: 1.04-1.08], P < 0.01), chronic obstructive pulmonary disease (HR 1.63, 95%CI: [1.01-2.64], P = 0.04), preoperative renal dysfunction (HR 3.08, 95%CI: [1.98-4.78], P < 0.001), New York Heart Association Class III/IV (HR 1.48, 95%CI: [1.04-2.10], P = 0.031), and mCVG (HR 2.15, 95%CI: [1.42-3.26], P < 0.001) were associated with higher risk of follow-up mortality. After propensity matching, the differences in mortality and reoperation remained significant. Conclusions: The Bentall-De Bono operation can be performed with consistently good results in experienced centers. Early outcomes are excellent regardless of the valve choice. In our study, the Bentall-De Bono operation with bCVG was associated with lower 10-year mortality but carried a higher risk of aortic reoperation. While the risk of reoperation is largely tied to valve choice, follow-up mortality is more likely to be influenced by patient comorbidities and risk factors.
BACKGROUND: Graft patency is the postulated mechanism for the benefits of coronary artery bypass grafting (CABG). However, systematic graft imaging assessment after CABG is rare, and there is a lack of contemporary data on the factors associated with graft failure and on the association between graft failure and clinical events after CABG. METHODS: We pooled individual patient data from randomized clinical trials with systematic CABG graft imaging to assess the incidence of graft failure and its association with clinical risk factors. The primary outcome was the composite of myocardial infarction or repeat revascularization occurring after CABG and before imaging. A 2-stage meta-analytic approach was used to evaluate the association between graft failure and the primary outcome. We also assessed the association between graft failure and myocardial infarction, repeat revascularization, or all-cause death occurring after imaging. RESULTS: Seven trials were included comprising 4413 patients (mean age, 64.4±9.1 years; 777 [17.6%] women; 3636 [82.4%] men) and 13 163 grafts (8740 saphenous vein grafts and 4423 arterial grafts). The median time to imaging was 1.02 years (Q1;Q3: 1.00;1.03). Graft failure occurred in 1487 (33.7%) patients and in 2190 (16.6%) grafts. Age (adjusted odds ratio [aOR], 1.08 [per 10-year increment] [95% CI, 1.01–1.15]; P =0.03), female sex (aOR, 1.27 [95% CI, 1.08–1.50]; P =0.004), and smoking (aOR, 1.20 [95% CI, 1.04–1.38]; P =0.01) were independently associated with graft failure, whereas statins were associated with a protective effect (aOR, 0.74 [95% CI, 0.63–0.88]; P <0.001). Graft failure was associated with an increased risk of myocardial infarction or repeat revascularization occurring between CABG and imaging assessment (8.0% in patients with graft failure versus 1.7% in patients without graft failure; aOR, 3.98 [95% CI, 3.54–4.47]; P <0.001). Graft failure was also associated with an increased risk of myocardial infarction or repeat revascularization occurring after imaging (7.8% versus 2.0%; aOR, 2.59 [95% CI, 1.86–3.62]; P <0.001). All-cause death after imaging occurred more frequently in patients with graft failure compared with patients without graft failure (11.0% versus 2.1%; aOR, 2.79 [95% CI, 2.01–3.89]; P <0.001). CONCLUSIONS: In contemporary practice, graft failure remains common among patients undergoing CABG and is strongly associated with adverse cardiac events.
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