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Background: As a subtype of pulmonary hypertension (PH), pulmonary veno-occlusive disease (PVOD) is devastating and life-threatening disease without effective therapy. Hydrogen has been reported to exhibits antioxidant and anti-inflammatory effects in a rat model induced by monocrotaline of PH. In this study, we investigated the effects of inhaled hydrogen gas on the prevention and treatment of PVOD induced by mitomycin C (MMC) in rats., Methods: PVOD was induced in female Sprague-Dawley rats through intraperitoneal injection of MMC at a concentration of 3 mg·kg - 1 ·wk - 1 for 2 weeks. Inhalation of hydrogen gas (H 2 ) was administered through a designed rat cage concurrently or two weeks after MMC administration. The severity of PVOD was assessed by using hemodynamic measurements and histological analysis. The expression levels of general control nonderepressible 2 (GCN2), nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1) and endothelial-to-mesenchymal transition (EndoMT) related proteins in lung tissue were measured. Levels of lipid peroxidation pro-inflammatory cytokines in serum were determined., Results: Inhaled H 2 improved hemodynamics and right heart function, reversed right ventricular hypertrophy, and prevented pulmonary vessel reconstitution in both prevention and treatment approaches. It decreased malondialdehyde (MDA) levels in the serum and the expression of NADPH oxidase 1 (NOX-1) in lung tissue. It regulated Nrf2/HO-1 signaling pathway and anti-inflammatory factor GCN2 in lung tissue, accompanied by a decrease in macrophages and pro-inflammatory cytokines. Our data suggested that H 2 inhalation effectively countered EndoMT induced by MMC, as evidenced by the detection of endothelial markers (e.g., VE-cadherin and CD31) and mesenchymal markers (e.g., vimentin and fibronectin). Further research revealed that H 2 preserved p-Smad3 and induced p-Smad1/5/9., Conclusion: Inhalation of H 2 effectively inhibits the pathogenesis of PVOD induced by MMC in rats. This inhibitory effect may be attributed to the antioxidant and anti-inflammatory properties of H 2 ., (© 2024. The Author(s).)

Objectives: Pulmonary vein obstruction (PVO) frequently occurs after repair of total anomalous pulmonary vein connection with progression of intimal hyperplasia from the anastomotic site toward upstream pulmonary veins (PVs). However, the understanding of mechanism in PVO progression is constrained by lack of data derived from a physiological model of the disease, and no prophylaxis has been established. We developed a new PVO animal model, investigated the mechanisms of PVO progression, and examined a new prophylactic strategy., Methods: We developed a chronic PVO model using infant domestic pigs by cutting and resuturing the left lower PV followed by weekly hemodynamic parameter measurement and angiographic assessment of the anastomosed PV. Subsequently, we tested a novel therapeutic strategy with external application of rapamycin-eluting film to the anastomotic site., Results: We found the pig PVO model mimicked human PVO hemodynamically and histopathologically. This model exhibited increased expression levels of Ki-67 and phospho-mammalian target of rapamycin in smooth muscle-like cells at the anastomotic neointima. In addition, contractile to synthetic phenotypic transition; that is, dedifferentiation of smooth muscle cells and mammalian target of rapamycin pathway activation in the neointima of upstream PVs were observed. Rapamycin-eluting films externally applied around the anastomotic site inhibited the activation of mammalian target of rapamycin in the smooth muscle-like cells of neointima, and delayed PV anastomotic stenosis., Conclusions: We demonstrate the evidence on dedifferentiation of smooth muscle-like cells and mammalian target of rapamycin pathway activation in the pathogenesis of PVO progression. Delivery of rapamycin to the anastomotic site from the external side delayed PV anastomotic stenosis, implicating a new therapeutic strategy to prevent PVO progression., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Stroke is a clinically important problem. A left atrial thrombus is known as a cause of ischaemic stroke. A pulmonary vein thrombus (PVT) is thought to be rare; however, PVT is common in elderly patients. Additionally, images of PVT with transoesophageal echocardiography (TEE) following treatment have not been well contrasted with that from either 64 or 80-slice multidetector CT (80-MDCT). The images of such changes depicted by TEE remain unknown. An 87-year-old man with hypertension was examined by 80-MDCT and TEE to check the cardiac thrombus. Although 80-MDCT did not depict the thrombus, TEE depicted the thrombus in the left atrium and right lower pulmonary vein (RLPV) clearly. After 6 months of rivaroxaban treatment, the thrombus in the RLPV decreased slightly and the thrombus in the left atrium became small and lucent, as estimated with TEE. Rivaroxaban decreased the size of the thrombus and changed the quality of the thrombus., Competing Interests: Conflicts of Interest: None declared., (2017 BMJ Publishing Group Ltd.)

Introduction: This practice survey is conducted to analyze clinical hematopoietic stem cell transplantation (HSCT) practice variability among centers in the WHO Eastern Mediterranean Region (EMRO), as represented by the Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) group., Method: This internet based survey was completed by the medical program directors of the EMBMT centers; 17 centers participated. The survey collected data on various clinical aspects of HSCT practice., Results: Consistency in pre HSCT cardiac (100%), pulmonary (82%) and viral screen (100%) was observed. Obtaining informed consent was universal. Pre-HSCT psychological assessment is practiced in 50% of the centers. All centers used single-bedded rooms with HEPA filters. Visitor policy during neutropenic phase and the use of gowns, masks or gloves when examining patients varied among centers. MRSA/VRE screen and use of low bacterial diet were applied in 65% and 82%, respectively. Anti-bacterial prophylaxis is employed in 58% (Auto-SCT) and 60% (Allo-SCT) of the centers. Drug choice varied (cotrimoxazole, ciprofloxacin, levofloxacin, piperacillin-tazobactam); 60% of the centers used penicillin prophylaxis in GVHD patients. PCP prophylaxis is applied in 58% (Auto-SCT) and 87% (Allo-SCT) of the centers; cotrimoxazole is usually used. Anti-viral prophylaxis with acyclovir or, less commonly, valacyclovir is used in 70% (Auto-SCT) and 93% (Allo-SCT) of centers. Anti-fungal prophylaxis is applied in 70% (Auto-SCT), 93% (myeloablative Allo-SCT) and 87% (reduced intensity [RIC] Allo-SCT). Fluconazole is used in all Auto-SCT and majority of Allo-SCT recipients; few centers used other agents (itraconazole, voriconazole, amphotericin B) in Allo-SCT. Prophylactic GCSF use varied among centers: Auto-SCT 77%, myeloablative Allo-SCT 33%, RIC Allo-SCT 27%. Use of ursodeoxycholic acid for venoocclusive disease (VOD) prophylaxis is variable: 60% (Allo-SCT) and 12% (Auto-SCT). Cyclosporine/methotrexate is the most commonly used GVHD prophylaxis in myeloablative Allo-SCT (93%); heterogeneity was seen in RIC SCT. Treatment of steroid refractory acute GVHD varied (ATG 53%, higher steroid dose 40%). CMV monitoring varied between antigenemia (53%) and PCR (40%) techniques. Pre-emptive anti CMV therapy is used in 86% of the centers, while 7% used routine CMV prophylaxis; 7% had no specific CMV management policy., Conclusion: Consistency was observed in areas of pre-SCT work up, use of single rooms, HEPA filters and GVHD prophylaxis. Heterogeneity is observed in other practice aspects including other isolation measures, anti-microbial prophylaxis, VOD prophylaxis, growth factor use and treatment of steroid refractory GVHD. Further studies are needed to probe the impact of such practice variations on post-transplant outcome and to ascertain the best clinical practice approach., (Copyright © 2013 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.)

A best evidence topic in cardiac surgery was constructed according to a structured protocol. The question addressed was, 'Is double or single patch for sinus venous atrial septal defect repair the better option in prevention of postoperative venous obstruction?' Altogether seventy nine papers were found using the reported search; ten papers were identified that provided the best evidence to answer the question. The authors, journal, date, country of publication, patient group, study type, relevant outcomes and results of were tabulated. Three hundred and thirty four patients had single-patch with 7 (2.1%) having venous obstruction (venous obstruction; defined as obstruction at the atriocaval anastomosis and/or the right superior pulmonary vein) while 130 had double-patch with 3 (2.3%) having venous obstruction. However, when the three randomised studies were reviewed, 101 had single-patch and 67 had double-patch with 7 (7%) and 4 (6%) having venous obstruction respectively. Similarly, another randomised study that considered solely the two surgical options with eighteen patients who had single-patch repair as group A and 19 patients who had double-patch repair as group B with six patients in group A and 2 patients in group B having significant superior vena cava-right atrium pressure gradient of more than 6 mmHg. Nine patients in group A had a significant gradient causing turbulence across the right superior pulmonary vein at the level of the patch, whereas no patients in group B had turbulence across the pulmonary vein. The double-patch technique technically offered better results in terms of superior vena cava narrowing and gradient across the pulmonary vein without any increase in complications. However, in order to reduce postoperative venous obstruction while using the single-patch repair method, the adoption of the transcaval approach yielded excellent results, with unobstructed pulmonary and systemic venous flow as in 141 patients who had this method of repair only one patient had venous obstruction. In conclusion, the evidence was in support of the adoption of double-patch or the use of the transcaval repair technique when the single patch technique was used as a better option to avoid venous obstruction.

The natural history of total pulmonary venous connection (TAPVC) is unfavorable per se. We describe a modified technique of intra-atrial repair in infants with supra- and infracardiac TAPVC. Twenty patients were treated. The median age at repair was 16 (range 3-62) days. Echocardiography and multi-detector row computed tomography were used to confirm the diagnosis. Our policy was to perform surgery on an urgent basis whenever there was a sign of severe pulmonary congestion or hypoxia. The procedures performed in cardiopulmonary bypass (CPB) were established in a standard fashion using bi-caval cannulation and moderate hypothermia. A novel modification of our surgical technique is the H-shaped instead of simple straight incision of pulmonary venous confluence and intra-atrial sewing. H-shaped incision of pulmonary venous confluence can increase the anastomotic area than simply straight-line incision and create a large anastomosis with maximal use of the venous confluence and atrial tissue. Intra-atrial repair can avoid torsion and rotation of the pulmonary veins. There were no operative deaths and no recurrent pulmonary venous obstruction was noted after a mean period of 2 ± 0.8 years (range: 12-20 months). Intra-atrial repair provides excellent results for primary repair of supra- and infracardiac TAPVC in infants., (Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Pulmonary venous obstruction (PVO) after correction of total anomalous pulmonary venous connection (TAPVC) frequently occurs due to intimal-hyperplasia and the required re-operation. We have developed a novel sustained-release drug delivery system, using Tacrolimus-eluting biodegradable nano-fiber (TEBN). It consists of nano-scale fiber composed of biodegradable polymer and Tacrolimus. This study evaluated the effects of TEBN for prevention of venous anastomotic stricture in a rat model to apply to PVO operation. Tacrolimus was incorporated into poly (L-lactide-co-glycolide). The venous stricture model was made by rat inferior vena cava anastomosis. The IVC anastomosis was covered with TEBN with 1.0 wt% Tacrolimus (n=12) or without TEBN as a control (n=12), and evaluated histologically at 1, 2, and 4 weeks after operation. The ratio of intimal area was significantly reduced in the TEBN group compared with the control group (ratio; 1 week: 0.43+/-0.26 vs. 0.07+/-0.04, P=0.04, 2 weeks: 0.39+/-0.19 vs. 0.05+/-0.02, P=0.01, 4 weeks: 0.31+/-0.15 vs. 0.09+/-0.04, P=0.03, control vs. TEBN, respectively). Histological findings showed endothelialization along the inner surface of the vein even in TEBN. The TEBN reduced intimal hyperplasia and preserved endothelialization even in a venous stricture. These results suggested that this strategy might be useful for prevention of recurrent PVO after TAPVC correction.

Nitric oxide (NO) is a potential new therapeutic agent for sickle cell disease (SCD). We investigated the effects of NO donor on hypoxia-induced acute lung injury that occurs when transgenic sickle cell SAD mice are exposed to chronic hypoxia, a model for lung vasoocclusive sickle cell events. In wild-type and SAD mice, intraperitoneal injection of S-nitrosoalbumin (NO-Alb) produced no significant hematologic changes under room air conditions, whereas it induced mild temporary hypotension and inhibition of platelet aggregation. NO-Alb administration (300 mg/kg ip twice a day, equivalent to 7.5 microM NO) in wild-type and SAD mice exposed to 46 h of hypoxia (8% oxygen) followed by 2 h of normoxia resulted in 1) reduction of the hypoxia-induced increase in blood neutrophil count, 2) prevention of hypoxia-induced increased IL-6 and IL-1beta levels in bronchoalveolar lavage, 3) reduction of the lung injury induced by hypoxia-reoxygenation, 4) prevention of thrombus formation, and 5) prevention of hypoxia-induced increase of lung matrix metalloproteinase-9 gene expression. These effects provide new insights into the possible use of NO-Alb in the treatment of acute lung injury in SCD.

Background: Despite theoretical advantages of absorbable suture in the growing vascular anastomosis, there has not been a documented advantage over nonabsorbable suture in preventing late anastomotic stenosis in total anomalous pulmonary venous connection (TAPVC)., Methods: We reviewed our experience from 1982 to 1994 with 65 hospital survivors of total TAPVC repair to examine the influence of suture type on survival and incidence of late pulmonary venous obstruction. From 1982 until 1988, we used continuous nonabsorbable polypropylene suture for the pulmonary venous-left atrial anastomosis in supracardiac, infracardiac, and mixed types of TAPVC: In 1989, we adopted a running absorbable polydioxanone suture technique. Cardiac catheterization and echocardiography were used to evaluate late pulmonary venous obstruction., Results: Late pulmonary venous obstruction occurred in 17% (4/23) of survivors after repair with polypropylene suture compared with 3.2% (1/32) after repair with polydioxanone suture (p < 0.05). There were no instances of late pulmonary venous obstruction in the intracardiac TAPVC group (0/10). All late pulmonary venous obstructions occurred within 16 months after operation. The actuarial 3-year and 5-year freedom from late pulmonary venous obstruction was 100% for intracardiac TAPVC, 96% for the polydioxanone group, and 81% for the polypropylene group. Five patients died late (5/65, 7.7%), 3 in the polypropylene suture group (3/23, 13%) and 2 in the polydioxanone group (2/32, 6%)., Conclusions: Continuous absorbable polydioxanone suture for the repair of TAPVC results in a low incidence of late pulmonary venous obstruction and death and appears to offer advantages over a continuous nonabsorbable suture. A continuous nonabsorbable suture may limit growth of a vascular anastomosis, particularly one involving a "low-pressure" anastomosis such as in the repair of TAPVC: