FC 104CARDIAC GEOMETRY, FUNCTION, AND REMODELING PATTENRS AND LUNG WATER CONTENT IN PATIENTS UNDER MAINTENANCE HEMODIALYSIS AND PERITONEAL DIALYSIS TREATMENT

Background and Aims Cardiovascular disease is the leading cause of mortality in patients with end-stage kidney disease (ESKD). Evidence on the possible echocardiographic differences between patients undergoing different dialysis modalities is scarce. This study aimed to evaluate differences in left (LA) and right atrial (RA) and left (LV) and right ventricular (RV) geometry, systolic and diastolic function, as well as lung water content in hemodialysis and peritoneal dialysis (PD) patients. Method A total of 38 hemodialysis and 38 PD patients receiving treatment for ≥3 months, matched in a 1:1 ratio for age, sex and dialysis vintage were included in this study. Lung ultrasound, two-dimensional and tissue-Doppler echocardiography were performed during an interdialytic day in hemodialysis and before a programmed follow-up visit in PD patients. To identify factors possible associated with LVH (left ventricular hypertrophy), we performed univariate and multivariate linear regression analyses in the total population studied. Results No significant differences were evidenced in ultrasound B-lines (4.00 [6.00] vs 3.00 [4.25]; p=0.623) between the two groups. Vena cava diameter (11.09±4.53 vs 14.91±4.30 mm; P<0.001) was significantly lower in hemodialysis patients. Indices of LA, RA, LV and RV dimensions were similar between the two groups. LVMi (116.91 [38.56] vs 122.83 [52.33] g/m2; P=0.767) was similar, but relative wall thickness (RWT) was marginally (0.40 [0.14] vs 0.45 [0.15] cm; P=0.055) lower in hemodialysis patients. LV hypertrophy prevalence, defined as LVMi values >95 or >115 g/m2 for female and male patients, was similar between groups (73.7% vs 71.1%; p=0.798), but relative wall thickness (RWT) was numerically lower (0.40 [0.14] vs 0.45 [0.15] cm; P=0.055) and fractional shortening (29.12±7.07% vs 23.37±8.84%; P=0.003) was significantly higher in patients under hemodialysis compared to those under PD. Hemodialysis patients presented mainly eccentric (normal RWT and increased LVMi), while PD patients presented mainly concentric LVH (increased RWT and increased LVMi). Left atrial (LA), right atrial (RA) and ventricular (RV) echocardiographic indices were again similar between the two study groups. Ventricular systolic function was similar between-groups, except for stroke volume (78.97 [24.24] vs 64.66 [27.35] ml; P=0.030) and cardiac output (5.75 [2.29] vs 4.93 [2.10] L/min; P=0.036) which were higher in hemodialysis. With regards to RV systolic function indices, RV systolic pressure (RVSP) was significantly lower in the hemodialysis compared to the PD group (20.37 [22.54] vs 27.68 [14.32] mmHg; P=0.009). All diastolic function indices were similar between the two groups. Prevalence of mitral valve (MV) regurgitation was significantly lower in the hemodialysis group (10.5% vs 39.5%; p=0.004). According to the results of multivariate linear regression analysis, only male gender (β=20.677, 95%CI: 3.479 to 37.874; P=0.019) and number of US-B lines (β=0.892, 95%CI:0.071 to 1.713; P=0.034) were independently associated with LVMi. Conclusion Hemodialysis and PD patients present similar volume overload, evaluated with lung ultrasound, and no significant differences in echocardiographic indices reflecting cardiac geometry, but different patterns of abnormal LV remodeling was evident in each dialysis modality, with hemodialysis presenting eccentric and PD concentric LVH. These results clearly support that PD is no better than HD with regards to cardiovascular stress, despite the fact that they experience a more stable volume status.

High molecular weight sodium hyaluronate improves survival of syndecan-1-deficient septic mice by inhibiting neutrophil migration

We investigated the role of endothelial glycocalyx and its component syndecan-1 protein in the pathophysiology of sepsis-induced vascular hyper-permeability and examined the therapeutic effects of high-molecular-weight sodium hyaluronate (HMW-SH). Methods Sepsis was induced by cotton smoke inhalation followed by intranasal administration of Pseudomonas aeruginosa in female (> 6 months) Balb/c and syndecan-1 knockout mice. Survival of mice, lung capillary endothelial glycocalyx integrity, lung water content, and vascular hyper-permeability were determined with or without HMW-SH treatment in these mice. Effects of HMW-SH on endothelial permeability and neutrophil migration were tested in in vitro setting. Results In septic wildtype mice, we found a severely damaged pulmonary microvascular endothelial glycocalyx and elevated levels of shed syndecan-1 in the circulation. These changes were associated with significantly increased pulmonary vascular permeability. In septic syndecan-1 knockout mice, extravascular lung water content was higher, and early death was observed. The administration of HMW-SH significantly reduced mortality and lung water content in septic syndecan-1 knockout mice, but not in septic wildtype mice. In in vitro setting, HMW-SH inhibited neutrophil migration and reduced cultured endothelial cell permeability increases. However, these effects were reversed by the addition of recombinant syndecan-1 ectodomain. Conclusions HMW-SH reduced lung tissue damage and mortality in the absence of syndecan-1 protein, possibly by reducing vascular hyper-permeability and neutrophil migration. Our results further suggest that increased shed syndecan-1 protein levels are linked with the inefficiency of HMW-SH in septic wildtype mice.

Maraviroc-Mediated Lung Protection following Trauma-Hemorrhagic Shock

Objectives.The peroxisome proliferator-activated receptor gamma (PPARγ) pathway exerts anti-inflammatory effects in response to injury. Maraviroc has been shown to have potent anti-inflammatory effects. The aim of this study was to investigate whether PPARγplays an important role in maraviroc-mediated lung protection following trauma-hemorrhage.Methods.Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35–40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of maraviroc (3 mg/kg, intravenously) with and without a PPARγinhibitor GW9662 (1 mg/kg, intravenously), GW9662, or vehicle was administered. Lung water content, tissue histology, and other various parameters were measured (n=8rats/group) 24 hours after resuscitation. One-way ANOVA and Tukey’s testing were used for statistical analysis.Results.Trauma-hemorrhage significantly increased lung water content, myeloperoxidase activity, intercellular adhesion molecule-1, interleukin-6, and interleukin-1βlevels. These parameters significantly improved in the maraviroc-treated rats subjected to trauma-hemorrhage. Maraviroc treatment also decreased lung tissue damage as compared to the vehicle-treated trauma-hemorrhaged rats. Coadministration of GW9662 with maraviroc abolished the maraviroc-induced beneficial effects on these parameters and lung injury.Conclusion.These results suggest that PPARγmight play a key role in maraviroc-mediated lung protection following trauma-hemorrhage.

Comparative analysis of fluid therapy in coronary artery bypass grafting surgery

Our prospective, randomized, simple-blinded, pilot study investigates the influence of fluid therapy by using balanced crystalloid solution, 4% solution of gelatin polysuccinate, and 6% hydroxyethyl starch 130/0.42 on the extravascular lung water content in patients with coronary artery bypass grafting surgery. The aim of fluid therapy was to maintain a global end diastolic volume index within 680-850 ml/m ². Transpulmonary thermodilution was used to determine an extravascular lung water index. Saturation of mixed venous blood, lactate, fluid balance, and hemodynamics were also investigated. It was shown that fluid therapy with the use of balanced crystalloid solution does not enhance the extravascular lung water content as compared with the use of colloid solutions. To achieve appropriate oxygen delivery, the effective infused volume of crystalloid solution was the double of that of colloid solutions.