Usefulness of two-dimensional echocardiographic parameters of the left side of the heart to predict right ventricular failure after left ventricular assist device implantation

Right ventricular failure (RVF) after left ventricular assist device (LVAD) placement is associated with increased morbidity and mortality. Echocardiography is a primary imaging method in the assessment of cardiac function; however, visualization of the right-sided heart is often technically difficult in patients with heart failure. We aimed to create a simple and generally applicable scoring system based on "left-sided echocardiographic parameters" to provide complementary information for predicting RVF after LVAD surgery. We reviewed 111 consecutive patients undergoing LVAD surgery from 2007 through 2010. Echocardiograms within 5 days before surgery were analyzed. RVF was defined as an unexpected RV assist devices requirement, nitric oxide inhalation >48 hours, and/or inotropic support >14 days. Thirty-five patients (32%) developed RVF. LV end-diastolic dimension (LVEDD) was smaller, LV ejection fraction was greater, and the left atrial diameter/LVEDD ratio was greater (p < 0.05 for all comparisons) in patients with RVF than in those without RVF. An RVF score (LV echocardiographic RVF score) was determined as a sum of points based on receiver operator characteristics analysis: LVEDD >78, 79 to 70, and <70 mm; LV ejection fraction ≤19%, 19% to 33%, and >33%; and left atrial diameter/LVEDD <0.63, 0.63 to 0.68, and >0.68; each variable was associated with 0 and 1 point and 2 points, respectively. LV echocardiographic RVF score ≥3 was associated with RVF with a sensitivity of 88.6% and score ≥5 with a specificity of 80.3%. In conclusion, patients with relatively small LV size, preserved LV contraction, and dilated left atrium were at higher risk for RVF after LVAD surgery. In conclusion, LV echocardiographic RVF score provides a novel tool to predict RVF after LVAD surgery, which does not involve invasive or technically complicated procedures.     

Toll-Like Receptor 4 Agonistic Antibody Promotes Innate Immunity against Severe Pneumonia Induced by Coinfection with Influenza Virus and Streptococcus pneumoniae

Coinfection with bacteria is a major cause of mortality during influenza epidemics. Recently, Toll-like receptor (TLR) agonists were shown to have immunomodulatory functions. In the present study, we investigated the effectiveness and mechanisms of the new TLR4 agonistic monoclonal antibody UT12 against secondary pneumococcal pneumonia induced by coinfection with influenza virus in a mouse model. Mice were intranasally inoculated with Streptococcus pneumoniae 2 days after influenza virus inoculation. UT12 was intraperitoneally administered 2 h before each inoculation. Survival rates were significantly increased and body weight loss was significantly decreased by UT12 administration. Additionally, the production of inflammatory mediators was significantly suppressed by the administration of UT12. In a histopathological study, pneumonia in UT12-treated mice was very mild compared to that in control mice. UT12 increased antimicrobial defense through the acceleration of macrophage recruitment into the lower respiratory tract induced by c-Jun N-terminal kinase (JNK) and nuclear factor kappaB (NF-κB) pathway-dependent monocyte chemoattractant protein 1 (MCP-1) production. Collectively, these findings indicate that UT12 promoted pulmonary innate immunity and may reduce the severity of severe pneumonia induced by coinfection with influenza virus and S. pneumoniae. This immunomodulatory effect of UT12 improves the prognosis of secondary pneumococcal pneumonia and makes UT12 an attractive candidate for treating severe infectious diseases.     

Tissue Distribution of Neospora caninum in Experimentally Infected Cattle

Histopathology and quantitative PCR (qPCR) were used to determine the tissue distribution of Neospora caninum in calves at 80 days postinfection. Our findings revealed that the most appropriate brain areas for researching N. caninum pathogenesis were the amygdala and hippocampus for qPCR and the corpus striatum and diencephalon for histopathology.     

Obstructive sleep apnea as a potential risk factor for aortic disease

Obstructive sleep apnea (OSA) is not only a cause of hypertension; it also possibly affects the pathogenesis and progression of aortic disease because an inspiratory effort-induced increase in negative intrathoracic pressure generates mechanical stress on the aortic wall. The objective of the present study was to examine the incidence by location of OSA as a complication in patients with aortic aneurysm and patients with aortic dissection (AD). An overnight sleep study was conducted in the following study groups: the aortic disease group (n?=?95) consisting of patients with thoracic aortic aneurysm (TAA, n?=?32), patients with abdominal aortic aneurysm (AAA, n?=?36), and patients with AD (n?=?27); and a control group (n?=?32), consisting of patients with coronary risk factors who were matched with the aortic disease group for age, gender, and body mass index (BMI). The 3% oxygen desaturation index (ODI) was significantly higher in all the TAA, AAA, and AD groups (P?=?0.045, P?=?0.003, and P?=?0.005, respectively) than in the control group. The incidence of moderate to severe OSA [apnea hypopnea index (AHI) ??15 events/h] was significantly higher in the first three groups (P?=?0.026, P?=?0.001, P?=?0.003, respectively) than in the control group, while no significant difference was found between the TAA group and the AAA group with respect to these variables. Furthermore, no significant differences were found between the thoracic AD subgroup and the abdominal AD subgroup with respect to AHI and 3% ODI, as well as with respect to the incidences of moderate to severe OSA. Patients with TAA, patients with AAA, and patients with AD showed high incidences of moderate to severe OSA. Although this result suggests that OSA may be one of risks for aortic disease, unelucidated mechanism(s) other than negative intrathoracic pressure may be involved in the pathogenesis of aortic disease.     

TGF-β1 Promotes Lymphangiogenesis during Peritoneal Fibrosis

Peritoneal fibrosis (PF) causes ultrafiltration failure (UFF) and is a complicating factor in long-term peritoneal dialysis. Lymphatic reabsorption also may contribute to UFF, but little is known about lymphangiogenesis in patients with UFF and peritonitis. We studied the role of the lymphangiogenesis mediator vascular endothelial growth factor-C (VEGF-C) in human dialysate effluents, peritoneal tissues, and peritoneal mesothelial cells (HPMCs). Dialysate VEGF-C concentration correlated positively with the dialysate-to-plasma ratio of creatinine (D/P Cr) and the dialysate TGF-β1 concentration. Peritoneal tissue from patients with UFF expressed higher levels of VEGF-C, lymphatic endothelial hyaluronan receptor-1 (LYVE-1), and podoplanin mRNA and contained more lymphatic vessels than tissue from patients without UFF. Furthermore, mesothelial cell and macrophage expression of VEGF-C increased in the peritoneal membranes of patients with UFF and peritonitis. In cultured mesothelial cells, TGF-β1 upregulated the expression of VEGF-C mRNA and protein, and this upregulation was suppressed by a TGF-β type I receptor (TGFβR-I) inhibitor. TGF-β1–induced upregulation of VEGF-C mRNA expression in cultured HPMCs correlated with the D/P Cr of the patient from whom the HPMCs were derived (P<0.001). Moreover, treatment with a TGFβR-I inhibitor suppressed the enhanced lymphangiogenesis and VEGF-C expression associated with fibrosis in a rat model of PF. These results suggest that lymphangiogenesis associates with fibrosis through the TGF-β–VEGF-C pathway.The decrease in ultrafiltration capacity that is associated with the high peritoneal solute transport that is observed after prolonged peritoneal dialysis (PD) treatment is a major reason for its discontinuation.^1–4 Several studies have shown that a higher peritoneal solute transport rate is associated with reduced survival of PD patients.^1,2,5 The characteristic features of chronic peritoneal damage in PD treatment are associated with submesothelial fibrosis and neoangiogenesis.^6,7 Analyses of the surface peritoneum showed no significant changes in vessel density with duration of PD.^6,8 In addition, the vessel density in patients with ultrafiltration failure (UFF) was significantly higher than the vessel density in normal individuals or non-PD patients, but it was not higher than the vessel density in patients undergoing PD.⁶ These findings suggest that factors other than increased vascular density may be involved in disease states associated with increased transport of peritoneal membranes. In addition, the relationship between peritoneal fibrosis and UFF remains obscure.Blood capillaries have a continuous basal lamina with tight interendothelial junctions and are supported by pericytes and smooth muscle cells. In contrast, lymphatic capillaries are thin-walled with a wide lumen and do not contain pericytes or basement membrane. The structures of lymphatic vessels are suitable for the removal of tissue fluid, cells, and macromolecules from the interstitium.^9–11 If lymphangiogenesis develops in the peritoneal membrane, absorption of the PD fluid could be increased and lead to UFF. An increase in the number of lymphatic vessels has recently been reported in several disease conditions, including tumor metastasis,^12–15 chronic respiratory inflammatory diseases,^16–18 wound healing,¹⁹ and renal transplant rejection.^20,21 We recently reported that lymphangiogenesis had developed in tubulointerstitial fibrosis of human renal biopsy specimens,²² and we also reported the mechanisms of lymphangiogenesis in rat unilateral ureteral obstruction models.²³The lymphatic absorption rate, which is measured by the rate at which intraperitoneally administered radioactive serum albumin or macromolecule dextran 70 disappears, is significantly higher in patients with UFF, and lymphatic reabsorption is considered to be one of the causes of UFF.^24–27 However, the results from these clinical approaches have been controversial.^28,29 In addition, little is known about the pathology and the process of lymphangiogenesis in patients with UFF and peritonitis.In this study, we investigated lymphangiogenesis and the expression of vascular endothelial growth factor-C (VEGF-C), which is a potentially important mediator of lymphangiogenesis, in human peritoneal tissues, PD effluent, and peritoneal mesothelial cells. We also explored VEGF-C induction by TGF-β1 in the human mesothelial cell line (Met-5A) and cultured human peritoneal mesothelial cells (HPMCs) from the spent PD effluent of patients with varying rates of peritoneal transport. Finally, we explored the relationship between peritoneal fibrosis and lymphangiogenesis in rats that were administered chlorhexidine gluconate (CG) into the abdominal cavity, which provides a model of chemically induced peritoneal inflammation/fibrosis.^30–32 This work is the first report to show that lymphangiogenesis is linked to the peritoneal fibrosis that is often associated with a high peritoneal transport rate.