Effect of Ulinastatin on Syndecan-2-Mediated Vascular Damage in IDH2-Deficient Endothelial Cells.

Syndecan-2 (SDC2), a cell-surface heparin sulfate proteoglycan of the glycocalyx, is mainly expressed in endothelial cells. Although oxidative stress and inflammatory mediators have been shown to mediate dysfunction of the glycocalyx, little is known about their role in vascular endothelial cells. In this study, we aimed to identify the mechanism that regulates SDC2 expression in isocitrate dehydrogenase 2 (IDH2)-deficient endothelial cells, and to investigate the effect of ulinastatin (UTI) on this mechanism. We showed that knockdown of IDH2 induced SDC2 expression in human umbilical vein endothelial cells (HUVECs). Matrix metalloproteinase 7 (MMP7) influences SDC2 expression. When IDH2 was downregulated, MMP7 expression was increased, as was TGF-ß signaling, which regulates MMP7. Inhibition of MMP7 activity using MMP inhibitor II significantly reduced SDC2, suggesting that IDH2 mediated SDC2 expression via MMP7. Moreover, expression of SDC2 and MMP7, as well as TGF-ß signaling, increased in response to IDH2 deficiency, and treatment with UTI reversed this increase. Similarly, the increase in SDC2, MMP7, and TGF-ß signaling in the aorta of IDH2 knockout mice was reversed by UTI treatment. These findings suggest that IDH2 deficiency induces SDC2 expression via TGF-ß and MMP7 signaling in endothelial cells.

CR6 interacting factor 1 deficiency promotes endothelial inflammation by SIRT1 downregulation.

AIMS: CR6 interacting factor 1 (CRIF1) deficiency impairs mitochondrial oxidative phosphorylation complexes, contributing to increased mitochondrial and cellular reactive oxygen species (ROS) production. CRIF1 downregulation has also been revealed to decrease sirtuin 1 (SIRT1) expression and impair vascular function. Inhibition of SIRT1 disturbs oxidative energy metabolism and stimulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-induced inflammation. Therefore, we hypothesized that both CRIF1 deficiency-induced mitochondrial ROS production and SIRT1 reduction play stimulatory roles in vascular inflammation. METHODS AND RESULTS: Plasma levels and mRNA expression of proinflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6) were markedly elevated in endothelium-specific CRIF1-knockout mice and CRIF1-silenced endothelial cells, respectively. Moreover, CRIF1 deficiency-induced vascular adhesion molecule-1 (VCAM-1) expression was consistently attenuated by the antioxidant N-acetyl-cysteine and NF-κB inhibitor (BAY11). We next showed that siRNA-mediated CRIF1 downregulation markedly activated NF-κB. SIRT1 overexpression not only rescued CRIF1 deficiency-induced NF-κB activation but also decreased inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and VCAM-1 expression levels in endothelial cells. CONCLUSIONS: These results strongly suggest that CRIF1 deficiency promotes endothelial cell inflammation by increasing VCAM-1 expression, elevating inflammatory cytokines levels, and activating the transcription factor NF-κB, all of which were inhibited by SIRT1 overexpression.

Point-of-Care Ultrasound-Guided Percutaneous Cannulation of Extracorporeal Membrane Oxygenation: Make it Simple.

BACKGROUND: Cannulation of the great vessels is required for extracorporeal membrane oxygenation (ECMO). Currently, there is no guideline for optimal imaging modalities during percutaneous cannulation of ECMO. OBJECTIVE: The purpose of this study was to describe percutaneous cannulation guided by point-of-care ultrasound (POCUS) for ECMO and compare it with fluoroscopy and landmark guidance. METHODS: Three groups (POCUS-, fluoroscopy-, and landmark-guided) of percutaneous cannulation for ECMO were analyzed retrospectively in a tertiary academic hospital. In the POCUS-guided group, visual confirmation of guidewire and cannula by ultrasound in both the access and return cannula were essential for successful cannulation. Fluoroscopy- and landmark-guided groups were cannulated with the conventional technique. RESULTS: A total of 128 patients were treated by ECMO during the study period, of which 94 (73.4%) cases were venoarterial ECMO. This included 56 cases of extracorporeal cardiopulmonary resuscitation. Also, there were 30 (23.4%) cases of venovenous ECMO and 4 (3.1%) cases of venoarteriovenous ECMO. A total of 71 (55.5%) patients were cannulated under POCUS guidance, and 43 (33.6%) patients were cannulated under fluoroscopy guidance and 14 (10.9%) patients were cannulated by landmark guidance. No surgical cut downs were required. Misplacement of cannula occurred in 3 (2.3%) cases. All three occurred in the landmark-guided group. CONCLUSIONS: POCUS-guided cannulation is comparable to fluoroscopy-guided cannulation in terms of avoiding cannula misplacement. In our experience, POCUS-guided cannulation is a useful strategy over fluoroscopy- and landmark-guided cannulation during peripheral ECMO.

Extracorporeal CPR and intra-aortic balloon pumping in tachycardia-induced cardiomyopathy complicating cardiac arrest.

Although tachycardia-induced cardiomyopathy (TIC) due to atrial fibrillation occurs frequently, it is under-recognized in clinical settings. TIC has a wide range of clinical manifestations, from asymptomatic tachycardia to cardiomyopathy leading to end stage heart failure. We present a case of a 48year-old-woman who presented as cardiogenic shock, and rapidly progressed to cardiac arrest from recently diagnosed but undertreated atrial fibrillation, resulting TIC in the emergency department (ED). She was rescued by extracorporeal cardiopulmonary resuscitation (E-CPR) for refractory cardiac arrest in the ED, and received concomitant intra-aortic balloon counterpulsation (IABP) support for severe left ventricular failure. Cardiogenic shock can present as an initial manifestation of TIC, and E-CPR and subsequent IABP support can be a valuable rescue therapy for severe TIC.

Phrenic Arterial Injury Presenting as Delayed Hemothorax Complicating Simple Rib Fracture.

Delayed hemothorax after blunt torso injury is rare, but might be associated with significant morbidity and mortality. We present a case of delayed hemothorax bleeding from phrenic artery injury in a 24-year-old woman. The patient suffered from multiple rib fractures on the right side, a right hemopneumothorax, thoracic vertebral injury and a pelvic bone fracture after a fall from a fourth floor window. Delayed hemothorax associated with phrenic artery bleeding, caused by a stab injury from a fractured rib segment, was treated successfully by a minimally invasive thoracoscopic surgery. Here, we have shown that fracture of a lower rib or ribs might be accompanied by delayed massive hemothorax that can be rapidly identified and promptly managed by thoracoscopic means.

IDH2 deficiency impairs mitochondrial function in endothelial cells and endothelium-dependent vasomotor function.

Mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2) plays an essential role protecting cells against oxidative stress-induced damage. A deficiency in IDH2 leads to mitochondrial dysfunction and the production of reactive oxygen species (ROS) in cardiomyocytes and cancer cells. However, the function of IDH2 in vascular endothelial cells is mostly unknown. In this study the effects of IDH2 deficiency on mitochondrial and vascular function were investigated in endothelial cells. IDH2 knockdown decreased the expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I, II and III, which lead to increased mitochondrial superoxide. In addition, the levels of fission and fusion proteins (Mfn-1, OPA-1, and Drp-1) were significantly altered and MnSOD expression also was decreased by IDH2 knockdown. Furthermore, knockdown of IDH2 decreased eNOS phosphorylation and nitric oxide (NO) concentration in endothelial cells. Interestingly, treatment with Mito-TEMPO, a mitochondrial-specific superoxide scavenger, recovered mitochondrial fission-fusion imbalance and blunted mitochondrial superoxide production, and reduced the IDH2 knockdown-induced decrease in MnSOD expression, eNOS phosphorylation and NO production in endothelial cells. Endothelium-dependent vasorelaxation was impaired, and the concentration of bioavailable NO decreased in the aortic ring in IDH2 knockout mice. These findings suggest that IDH2 deficiency induces endothelial dysfunction through the induction of dynamic mitochondrial changes and impairment in vascular function.

Extracorporeal cardiopulmonary resuscitation in bedside echocardiography-diagnosed massive pulmonary embolism.

Acute pulmonary embolism (PE) is one of the major causes of inhospital cardiac arrest as well as out-of-hospital cardiac arrest. Bedside diagnosis of acute PE in the emergency department (ED) can be challenging, especially in a cardiac arrest setting. Even if the early diagnosis of an acute massive PE had been made, hemodynamic instability may be worsened unless obstructive shock gets resolved. We present a case of a 46-year-old woman who developed pulseless electrical activity (PEA) after complaining of weakness and dyspnea in an ambulance, presumptively diagnosed as acute PE by bedside focused echocardiography. She received thrombolytic therapy and was rescued by extracorporeal cardiopulmonary resuscitation for recurrent PEA arrest in the ED. Focused bedside echocardiography provides a rapid diagnostic adjunct, and extracorporeal cardiopulmonary resuscitation can be a valuable rescue therapy for PEA arrest from massive PE.

An unusual case of candidemia presenting as acute respiratory distress syndrome after a small bowel bezoar removal operation.

We report a rare case of sepsis with acute respiratory distress syndrome (ARDS) caused by Candida parapsilosis and Candida famata after a small bowel bezoar operation. The patient was successfully treated with intensive care including mechanical ventilation and systemic antifungal therapy. A strong association was observed between the intestinal obstruction caused by the bezoar and candidemia presenting as ARDS. This is the first case in which candidemia has led to ARDS after a bezoar removal operation in a patient who was neither immunocompromised nor self-administering an illicit intravenous drug.

Feasibility and early outcomes of intensivist-led critical care after major trauma in the Korean ICU.

PURPOSE: Substantial evidence supports the benefits of an intensivist model of critical care delivery. However, currently, this mode of critical care delivery has not been widely adopted in Korea. We hypothesized that intensivist-led critical care is feasible and would improve ICU mortality after major trauma. MATERIALS AND METHODS: A trauma registry from May 2009 to April 2011 was reviewed retrospectively. We evaluated the relationship between modes of ICU care (open vs. intensivist) and in-hospital mortality following severe injury [Injury Severity Score (ISS)>15]. An intensivist-model was defined as ICU care delivered by a board-certified physician who had no other clinical responsibilities outside the ICU and who is primarily available to the critically ill or injured patients. ISS and Revised Trauma Score were used as measure of injury severity. The Trauma and Injury Severity Score methodology was used to calculate each individual patient's probability of survival. RESULTS: Of the 251 patients, 57 patients were treated by an intensivist [intensivist group (IG)] while 194 patients were not [non-intensivist group (NIG)]. The ISS of IG was significantly higher than that for NIG (26.5 vs. 22.3, p=0.023). The hospital mortality rate for IG was significantly lower than that for NIG (15.8% and 27.8%, p<0.001). CONCLUSION: The intensivist model of critical care is feasible, and there is room for improvement in the care of major trauma patients. Although trauma systems take time to mature, future studies are needed to evaluate the best model of critical care delivery for severely injured patients in Korea.

Atypical transient stress-induced cardiomyopathies with an inverted Takotsubo pattern in sepsis and in the postpartal state.

Several cases of inverted Takotsubo cardiomyopathy--a variant form with hyperdynamic left ventricular apex and akinesia of the left ventricular base and mid-portion--have been reported recently, especially in association with cerebrovascular accidents and catecholamine cardiomyopathies. Herein, we describe 2 cases of inverted Takotsubo cardiomyopathy: one that occurred in a middle-aged woman who had a septic condition, and another in a young woman who was in the postpartal state. Such cases have not been reported previously.

Cardiac surgery in a patient with idiopathic aplastic anemia: a case report.

Major surgery in a patient with pancytopenia might be associated with increased surgical risks, especially for bleeding and infection. A 66-yr-old man was admitted to the hospital due to shortness of breath. His dyspnea was classified by the New York Heart Association (NYHA) as functional class III. Prior to admission, he had a 5-yr history of medical management for idiopathic aplastic anemia. The severity of aplastic anemia of the patient was graded as non-severe aplastic anemia. Echocardiography revealed reduced left ventricular function and severe aortic valve regurgitation (grade IV) with left ventricular end diastolic dimension measuring 87 mm. Because of dyspnea and echocardiographically documented aortic valve insufficiency, the patient underwent elective aortic valve replacement. Although extracorporeal circulation for valve operations might be associated with aggravation of impaired blood cell function, the patient recovered from surgery uneventfully. Here, we report a successful cardiac surgery with extracorporeal cardiopulmonary bypass in a patient with severe aortic valve insufficiency and concomitant idiopathic aplastic anemia.

Heart transplantation. A retrospective analysis of the long-term results.

Long-term results of orthotopic heart transplantation vary among different institutions. The purpose of the present study was to assess the factors, which might affect long-term survival and complications. Between November 1992 and July 2003, 112 heart transplantations (M/F=89:23) were performed. The standard technique was used in the first 57 patients and the bicaval technique in the latter 55 patients. Indications for transplantation in decreasing order of frequency were dilated cardiomyopathy (75%), ischemic cardiomyopathy (7%), and others (18%). The mean follow up duration was 51.8 +/- 31.3 months with 98 patients remaining alive. Preoperatively, all patients were either in NYHA functional class III or IV. Postoperatively, all patients showed improvement to functional class II or I, except 3 patients that remained in NYHA class III. The mean number of rejection cases within the first year was 0.6 +/- 0.8, with humoral rejection noted in 3 cases. The graft vascular disease (GVD)-free survival at 3 and 5 years was 96% and 83%, respectively. The 7-year survival after heart transplantation was 84%. There were 16 deaths, of which infection (n=4) was the most common followed by rejection (n=3), and malignancy (n=2). The present long-term results, were relatively superior to those seen in western countries. The relatively low GVD-free survival rate is thought to have contributed. The complications encountered after transplantation were mostly immunosuppressive drug related, suggesting further potentials for improvement in long-term survival.