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Objectives: Systemic inflammation evoked by cardiopulmonary bypass (CPB) leads to acute lung injury (ALI) and respiratory failure. Although recombinant human soluble thrombomodulin (rTM) consists of three domains (D1-3), is reported to attenuate systemic inflammation through the N-terminal lectin-like domain (D1), anticoagulant domain (D2) may exacerbate coagulopathy after CPB. We investigated the potential of selective D1 against CPB-mediated ALI free from anticoagulant effects using a rat CPB model., Methods: Rats were divided into three groups: control (CPB alone, n = 5), D1 (CPB + D1, n = 4), and D123 (CPB + D123, n = 6). D1 or D123 was administrated to the rats of each group before CPB establishment. Blood samples are collected before, during and after CPB. Blood coagulability was assessed by a coagulation analyzer. Lung samples are collected at 1 h after the termination of CPB for histological analyses., Results: D123 group exhibited significantly prolonged glass beads-activated clotting time with heparinase after CPB compared to that in control group, whereas no significant prolongation in control and D1 group (control vs. D1 vs. D123: 65.4 ± 9.2 vs. 65.3 ± 10.9 vs. 83.5 ± 4.6 s, p = 0.036 [control vs. D123], 0.99 [control vs. D1]) indicating the absence of anticoagulant activities of D1. Histological studies revealed less congestion, edema, inflammation, and hemorrhage in both D1 and D123 groups compared to those in control group indicating protective effects of both D1 and D123 against ALI mediated by CPB., Conclusions: N-terminal lectin-like domain of rTM may reduce the risk of ALI without anticoagulant effects.

Background: Cardiopulmonary bypass (CPB) may induce systemic inflammatory responses causing acute lung injury. Recombinant human soluble thrombomodulin (rTM) is reported to attenuate the secretion of inflammatory cytokines and the high-mobility group box 1 (HMGB1) protein, which is critical in controlling systemic inflammation and apoptosis. We investigated the protective effects of rTM on CPB-induced lung injury in a rat model., Methods: Eighteen male Sprague-Dawley rats were divided into 3 groups: sham, control (CPB alone), and rTM (CPB + rTM). CPB was conducted in the control group and the rTM group. A bolus of rTM (3 mg/kg) was administered to the rTM group rats before CPB establishment., Results: The ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen only dropped markedly from before CPB in the control group (P < .001). Serum tumor necrosis factor α, interleukin (IL) 6, and HMGB1 levels were significantly higher in the control group after CPB. Pathologic study revealed significantly more severe congestion, alveolar hemorrhage, neutrophil accumulation, and edema, and the number of lung cells expressing HMGB1 increased in the control group. The mRNA expression levels of tumor necrosis factor α, IL-6, IL-1β, and HMGB1 in the control group were significantly higher than those in other groups. According to Western blot analysis, nuclear factor-κB p65 in lung tissue was significantly downregulated in the rTM group. The number of apoptotic cells and the protein of cleaved Caspase-3 were reduced in the rTM group., Conclusions: These results suggest that rTM prevents acute lung injury through attenuating inflammation and apoptosis during and after CPB in a rat model., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Systemic inflammation after prolonged cardiopulmonary bypass (CPB) can cause serious multiorgan system dysfunction. Mesenchymal stem cells (MSCs) are reported to reduce inflammation and attenuate immune response. We have focused on fetal membrane (FM) as a source to provide a large number of MSCs (FM-MSCs). Allogeneic administration of FM-MSCs has been reported to mitigate autoimmune myocarditis or glomerulonephritis. The aim of this study was to investigate whether allogeneic FM-MSCs attenuate systemic inflammatory responses and lung injury in a rat CPB model., Methods: Male Lewis rats (major histocompatibility complex haplotype: RT-1l) were divided randomly into 3 groups (n = 7 each): cannulation alone (sham group), CPB alone (control group), and CPB + MSC (MSC group). An experimental rat CPB model was established, and CPB was maintained for 30 minutes. In the MSC group, MSCs (1 × 10 6  cells) derived from the FM of ACI rats with a different major histocompatibility complex haplotype (RT-1a) were administrated intravenously before CPB initiation., Results: Serum concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-1β in the MSC group were significantly lower compared with the control group after CPB. Similarly, mRNA expression of proinflammatory cytokines in the lung was lower in the MSC group. Allogeneic administration of FM-MSCs remarkably decreased the lung injury score, protected alveolar structure, inhibited neutrophil infiltration to the lung interstitium, and stimulated cytoprotective cytokine production in the lung., Conclusions: Allogeneic transplantation of FM-MSCs may be a potent strategy to prevent CPB-induced systemic inflammation and acute lung injury by suppressing the expression of inflammatory cytokines and promoting protective factors in the lung., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Acute kidney injury (AKI) is a common complication accompanying cardiopulmonary bypass (CPB) and is independently associated with increased morbidity and death. Diabetes mellitus increases the risk for AKI after CPB. Epigallocatechin-3-gallate (EGCG) is a major component of the polyphenolic fraction of green tea, which possesses cardioprotective activities, as previously reported. We hypothesized that EGCG also possesses a renoprotective effect through its diverse biochemical properties and assessed the effect on renal function after CPB for diabetic rats., Methods: Goto-Kakizaki rats developing type 2 diabetes mellitus were randomly assigned to one of the following groups: sham (n = 10), CPB (CPB alone, n = 9), or EGCG (CPB + EGCG, n = 10). CPB was conducted for 30 minutes at a flow rate of 100 mL/kg/min in the CPB and EGCG groups. Rats assigned to the EGCG group were administrated EGCG solution orally for 2 weeks before CPB. We evaluated renal biochemical or histologic changes at 24 hours after CPB., Results: Compared with the CPB group, the EGCG group exhibited milder tubular injury histologically (p < 0.0001) and reduced expression of kidney injury molecule-1, a biomarker for renal tubular injury (p < 0.0001) and 8-hydroxy-2'-deoxyguanosine (p < 0.01), indicating attenuated oxidant stress., Conclusions: Preoperative oral administration of EGCG ameliorates AKI in a CPB model of diabetic rats through antioxidative properties. This simple method could be applied in a clinical setting as a prophylactic renal protection against AKI after CPB, especially for high-risk patients with diabetes mellitus., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We report the case of a 68-year-old man with progressive heart failure due to effusive-constrictive pericarditis. During approximately 1 month, echocardiography revealed rapid progression from pericarditis with effusion without tamponade to pericardial thickening and diastolic dysfunction. Cardiac catheterization revealed that the pressure in the right heart chambers remained high after pericardiocentesis. The patient was rescued by aggressive pericardiectomy and sharp dissection of the epicardium into small fragments. This on-pump beating-heart surgery is known as the waffle procedure.

Open in new tab Download slide Open in new tab Download slide OBJECTIVES To investigate risk factors for mortality after systemic-to-pulmonary (SP) shunt procedures in patients with a functionally univentricular heart using the Japan Cardiovascular Surgery Database registry. METHODS Clinical data from 75 domestic institutions were collected. Overall, 812 patients with a functionally univentricular heart who underwent initial SP shunt palliation were eligible for analysis. Patients with pulmonary atresia with an intact ventricular septum and patients with a SP shunt as part of the Norwood procedure were excluded. Risk factors for 30- and 90-day mortalities were analysed using a logistic regression model. RESULTS Median age and body weight at SP shunt placement were 41 days and 3.6 kg, respectively. Modified Blalock–Taussig shunt, central shunt and other types of SP shunts were applied in 689 (84.9%), 94 (11.8%) and 30 (3.7%) patients, respectively. Cardiopulmonary bypass was utilized in 410 patients (51%) for 128 min (median, 19–561). There were 411 isolated SP shunt procedures. Median hospital stay was 27 days, and 742 (91.4%) patients were discharged. The 30- and 90-day mortality rates were 3.4% and 6.0%, respectively. Placement of a central shunt was identified as a risk factor for 30-day mortality, while lower body weight, preoperative ventilator support, right atrial isomerism and coexistence of major aortopulmonary collateral arteries and an unbalanced atrioventricular septal defect were identified as risk factors for 90-day mortality. CONCLUSIONS SP shunt carries a high mortality rate in patients with a functionally univentricular heart when it is performed in smaller patients with complex cardiac anomalies. [ABSTRACT FROM AUTHOR]

Background: Liver cirrhosis is a major risk factor for cardiac surgery using cardiopulmonary bypass. However, percutaneous coronary intervention (PCI) or off-pump coronary artery bypass graft surgery (OPCABG) may be a less invasive alternative strategy. Methods: Among the 9,877 patients undergoing first PCI or CABG enrolled in the CREDO-Kyoto Registry (a registry of first-time PCI and CABG patients in Japan), 332 patients diagnosed with liver cirrhosis were entered into the study (age 67.1 ± 9.4 years; 246 male). Liver cirrhosis was diagnosed by liver biopsy or signs of portal hypertension with characteristic morphologic liver and spleen changes. Results: A total of 233 patients received PCI, 58 conventional on-pump CABG (CCABG), and 41 OPCABG. Median follow-up was 3.3 years. The PCI group included less complex coronary lesions such as triple vessel and left main disease (p < 0.01 each). Propensity score adjusted in-hospital mortality after CCABG or OPCABG was higher than that after PCI; however, the differences were not significant (odds ratio [95% confidence interval]: 6.84 [0.52 to 90.8], p = 0.14 for CCABG versus PCI; and 1.86 [0.08 to 45.8], p = 0.71 for OPCABG versus PCI). Adjusted overall mortality after CCABG or CABG was lower than that after PCI, but the differences were not significant (0.66 [0.31 to 1.40], p = 0.28; and 0.64 [0.28 to 1.49], p = 0.31, respectively). Approximately two thirds of patients died of noncardiovascular morbidities (malignancies, including hepatocarcinoma, or hepatic decompression). Conclusions: Because overall noncardiovascular mortality is high among patients with liver cirrhosis, complete revascularization may not be associated with better survival outcomes. Further study is warranted to determine the impact of a coronary revascularization strategy for liver cirrhosis patients. [Copyright &y& Elsevier]

Objective: Treatment of ischemic mitral regurgitation accompanied by strong tethering remains a challenge. Undersized ring annuloplasty is frequently associated with residual/recurrent mitral regurgitation caused by mitral-leaflet tethering. Although chordal cutting is a simple procedure for repairing severe tethering of the anterior mitral leaflet, it often affects mitral valvular-ventricular continuity. In this study, using 3-dimensional echocardiography, we investigated the effects of “chordal translocation” on the geometry of the mitral components in a canine model of acute ischemic mitral regurgitation. Methods: In 6 mongrel dogs, under cardiopulmonary bypass with cardiac arrest, artificial chordae were implanted to each papillary-muscle tip and passed through the midseptal annulus to an external tourniquet to control the tension of the stitch thereafter. Subsequently, secondary chordae were cut near their point of attachment to the anterior leaflet. After weaning from cardiopulmonary bypass, acute ischemic mitral regurgitation was induced by ligating the obtuse marginal branches. We obtained data in 2 states of the artificial chordae: relaxation (simulating chordal cutting) and gentle traction (simulating chordal translocation). Results: In the chordal translocation state versus the chordal cutting state, the left ventricle ejection fraction (42.6% ± 2.9% vs 33.2% ± 2.3%, P < .0001), preload recruitable stroke work (54.8 ± 2.7 mm Hg vs 34.1 ± 2.2 mm Hg, P = .0002), and end-systolic elastance (6.7 ± 0.5 mm Hg/mL vs 4.2 ± 0.2 mm Hg/mL, P = .0013) improved markedly. The mitral-valve tethering volume, defined as the volume enclosed by the mitral annulus and 2 leaflets, was smaller in the chordal translocation state than in the chordal cutting state (812 ± 88 mm3 vs 1213 ± 41 mm3, P = .03). In the chordal translocation state (CT-1 and CT-2) versus the chordal cutting state, the posterior mitral-leaflet tethering area (15.7 ± 0.7 mm2 vs 25.1 ± 1.2 mm2, P < .0001 for CT-1 and 15.0 ± 0.7 mm2 vs 25.1 ± 1.2 mm2, P < .0001 for CT-2) showed a greater improvement than the anterior mitral-leaflet tethering area (41.0 ± 0.7 mm2 vs 46.1 ± 1.3 mm2 for CT-1, P = .01 and 812 ± 88 mm2 vs 1213 ± 41 mm2 for CT-2, P = .03). The mitral annular geometry did not differ between the states. Conclusion: Compared with chordal cutting alone, chordal translocation improved both the left ventricle function and mitral geometry in a canine model of acute ischemic mitral regurgitation. Chordal translocation may be beneficial because it ameliorates the tethering of both the anterior and posterior leaflets, which is aggravated by mitral annuloplasty alone. [Copyright &y& Elsevier]

An 8-year-old girl became ventilator-dependent due to severe bronchiolitis obliterans/interstitial pneumonia caused by cord-blood cell transplantation for neuroblastoma. Her mother''s right lower lobe was twice as large as her right chest cavity. She successfully underwent living-donor, right, single-lobe lung transplantation and simultaneous left pneumonectomy under conditions of cardiopulmonary bypass. At 18 months after transplantation, the patient returned to school life and is currently able to carry out daily activities without supplemental oxygen. [Copyright &y& Elsevier]