Thiol-catalyzed formation of NO-ferroheme regulates intravascular NO signaling.

Nitric oxide (NO) is an endogenously produced signaling molecule that regulates blood flow and platelet activation. However, intracellular and intravascular diffusion of NO are limited by scavenging reactions with several hemoproteins, raising questions as to how free NO can signal in hemoprotein-rich environments. We explore the hypothesis that NO can be stabilized as a labile ferrous heme-nitrosyl complex (Fe2+-NO, NO-ferroheme). We observe a reaction between NO, labile ferric heme (Fe3+) and reduced thiols to yield NO-ferroheme and a thiyl radical. This thiol-catalyzed reductive nitrosylation occurs when heme is solubilized in lipophilic environments such as red blood cell membranes or bound to serum albumin. The resulting NO-ferroheme resists oxidative inactivation, is soluble in cell membranes and is transported intravascularly by albumin to promote potent vasodilation. We therefore provide an alternative route for NO delivery from erythrocytes and blood via transfer of NO-ferroheme and activation of apo-soluble guanylyl cyclase.

Echocardiographic features of right ventricle in septic patients with elevated central venous pressure.

BACKGROUND: Elevated central venous pressure (CVP) is deemed as a sign of right ventricular (RV) dysfunction. We aimed to characterize the echocardiographic features of RV in septic patients with elevated CVP, and quantify associations between RV function parameters and 30-day mortality. METHODS: We retrospectively reviewed a cohort of septic patients with CVP ≥ 8 mmHg in a tertiary hospital intensive care unit. General characteristics and echocardiographic parameters including tricuspid annular plane systolic excursion (TAPSE), pulmonary vascular resistance (PVR) as well as prognostic data were collected. Associations between RV function parameters and 30-day mortality were assessed using Cox regression models. RESULTS: Echocardiography was performed in 244 septic patients with CVP ≥ 8 mmHg. Echocardiographic findings revealed that various types of abnormal RV function can occur individually or collectively. Prevalence of RV systolic dysfunction was 46%, prevalence of RV enlargement was 34%, and prevalence of PVR increase was 14%. In addition, we collected haemodynamic consequences and found that prevalence of systemic venous congestion was 16%, prevalence of RV-pulmonary artery decoupling was 34%, and prevalence of low cardiac index (CI) was 23%. The 30-day mortality of the enrolled population was 24.2%. In a Cox regression analysis, TAPSE (HR:0.542, 95% CI:0.302-0.972, p = 0.040) and PVR (HR:1.384, 95% CI:1.007-1.903, p = 0.045) were independently associated with 30-day mortality. CONCLUSIONS: Echocardiographic findings demonstrated a high prevalence of RV-related abnormalities (RV enlargement, RV systolic dysfunction and PVR increase) in septic patients with elevated CVP. Among those echocardiographic parameters, TAPSE and PVR were independently associated with 30-day mortality in these patients.

A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning.

Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC-treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 µm) and nitric oxide (100 µm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 µm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning.

Physicians' abilities to obtain and interpret focused cardiac ultrasound images from critically ill patients after a 2-day training course.

BACKGROUND: This study aimed to determine whether a focused 2-day cardiac ultrasound training course could enable physicians to obtain and interpret focused cardiac ultrasound (FCU) images from critically ill patients. METHODS: We retrospectively reviewed the FCU images submitted by the physicians who attended a 2-day FCU training courses. Three experienced trainers reviewed the images separately. They determined whether the images were assessable and scored the images on an 8-point scale. They also decided whether the physicians provided correct responses for visual estimations of the left ventricular ejection fraction (LVEF) and right ventricle (RV) dilatation and septal motion. RESULTS: Among the 327 physicians, 291 obtained images that were considered assessable (89%). The scores for parasternal short-axis view were lower than those obtained for other transthoracic echocardiographic views, p < 0.001. More physicians provided incorrect appraisals of LVEF than of RV dilatation and septal motion (19.9% vs. 3.1%, p < 0.001). The percentages of incorrect answers by LVEF category were as follows: 34.8% on images of LVEF < 30, 24.7% on images of LVEF 30-54, and 16.4% on images of LVEF ≥55%, p < 0.001. A logistic regression analysis showed that patients with abnormal LVEF were associated with physicians' incorrect assessment of LVEF, with an odds ratio of 1.923 (95% confidence interval (CI):1.071-3.456, p = 0.029). CONCLUSIONS: A large proportion of physicians could obtain and interpret FCU images from critically ill patients after a 2-day training course. However, they still scored low on the parasternal short-axis view and were more likely to make an incorrect assessment of LVEF in patients with abnormal left ventricular systolic function.

Prognostic implications of tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio in septic shock patients.

BACKGROUND: To explore the association between the ratio of tricuspid annular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP), and long- and short-term outcomes in mechanically ventilated septic shock patients. METHODS: Septic shock patients admitted to the intensive care unit (ICU) were screened for enrollment. Echocardiographic parameters including TAPSE and tricuspid regurgitation velocity, haemodynamic and respiratory parameters, and prognostic data were obtained. RESULTS: One hundred eighteen subjects were enrolled in this study, among whom 75 survived and 43 died at the one-year follow-up. ROC curve analysis revealed that the TAPSE/PASP ratio was able to assess one-year all-cause mortality with an area under the curve of 0.817 (95% CI: 0.739-0.896, p < 0.001) and the optimal cutoff value was 0.50 mm/mmHg. Kaplan-Meier survival analysis showed that one-year all-cause mortality was significantly higher in patients with TAPSE/PASP ≤0.5 mm/mmHg than in patients with TAPSE/PASP > 0.5 mm/mmHg (log-rank 32.934, p < 0.001). According to the Cox regression survival analyses, the TAPSE/PASP ratio was independently associated with one-year all-cause mortality (HR 0.007, 95% CI:0.000-0.162, p = 0.002) and ICU mortality (HR 0.027, 95% CI:0.001-0.530, p = 0.017). According to the multivariable analysis, the TAPSE/PASP ratio was an independent variable associated with mechanical ventilation (MV) duration (standard coefficient - 0.240, p = 0.010). CONCLUSION: The TAPSE/PASP ratio demonstrated prognostic value for one-year all-cause mortality, ICU mortality and MV duration in mechanically ventilated septic shock patients.

Prognostic Value of Tricuspid Annular Plane Systolic Excursion and Right Ventricular Outflow Tract Fractional Shortening in Mechanically Ventilated Septic Patients.

OBJECTIVE: The authors aimed to explore whether tricuspid annular plane systolic excursion (TAPSE) and right ventricular outflow fractional shortening (RVOT-FS) were associated with long-term prognosis in mechanically ventilated septic patients. DESIGN: A prospective observational study. SETTING: A tertiary hospital intensive care unit (ICU). PARTICIPANTS: One hundred eighty-one septic patients who were on mechanical ventilation. INTERVENTIONS: Echocardiography was performed within 24 hours of ICU admission. MEASUREMENTS AND MAIN RESULTS: Several echocardiographic parameters, including TAPSE and RVOT-FS, as well as prognostic information, were collected. A Cox regression survival analysis showed that TAPSE was independently associated with one-year all-cause mortality (hazard ratio [HR] 0.407, 95% confidence interval [CI]: 0.200-0.827, p = 0.013), but ROVT-FS was not (HR 0.997, 95% CI: 0.970-1.025, p = 0.828). ROC analysis showed that the optimal cutoff value for TAPSE and RVOT-FS to determine one-year mortality was TAPSE <18 mm and RVOT-FS <40%. The one-year mortality in patients with low TAPSE (n = 88) and in patients with both low TAPSE and low RVOT-FS (n = 60) was 45.5% and 48.3%, respectively; p = 0.724. In a multivariate analysis, RVOT-FS did not add significant prognostic information to that provided by TAPSE <18 mm (p = 0.197). CONCLUSIONS: TAPSE was an independent predictor of one-year all-cause mortality in mechanically ventilated septic patients. RVOT-FS was not associated with one-year mortality and added no prognostic value to TAPSE in these patients.

WRN is recruited to damaged telomeres via its RQC domain and tankyrase1-mediated poly-ADP-ribosylation of TRF1.

Werner syndrome (WS) is a progeroid-like syndrome caused by WRN gene mutations. WS cells exhibit shorter telomere length compared to normal cells, but it is not fully understood how WRN deficiency leads directly to telomere dysfunction. By generating localized telomere-specific DNA damage in a real-time fashion and a dose-dependent manner, we found that the damage response of WRN at telomeres relies on its RQC domain, which is different from the canonical damage response at genomic sites via its HRDC domain. We showed that in addition to steady state telomere erosion, WRN depleted cells are also sensitive to telomeric damage. WRN responds to site-specific telomeric damage via its RQC domain, interacting at Lysine 1016 and Phenylalanine1037 with the N-terminal acidic domain of the telomere shelterin protein TRF1 and demonstrating a novel mechanism for WRN's role in telomere protection. We also found that tankyrase1-mediated poly-ADP-ribosylation of TRF1 is important for both the interaction between WRN and TRF1 and the damage recruitment of WRN to telomeres. Mutations of potential tankyrase1 ADP-ribosylation sites within the RGCADG motif of TRF1 strongly diminish the interaction with WRN and the damage response of WRN only at telomeres. Taken together, our results reveal a novel mechanism as to how WRN protects telomere integrity from damage and telomere erosion.

Tricuspid annular plane systolic excursion and central venous pressure in mechanically ventilated critically ill patients.

BACKGROUND: The tricuspid annular plane systolic excursion (TAPSE) is commonly recommended for estimating the right ventricular systolic function. The central venous pressure (CVP), which is determined by venous return and right heart function, was found to be associated with right ventricular outflow fractional shortening. This study thus aimed to investigate the relationship between the TAPSE and CVP in mechanically ventilated critically ill patients. METHODS: This is a prospective observational study. From October 1 to December 31, 2017, patients admitted to the intensive care unit with CVP monitoring and controlled mechanical ventilation were screened for enrolment. Echocardiographic parameters, including the TAPSE, mitral annular plane systolic excursion (MAPSE), left ventricular ejection fraction (LVEF), and internal diameter of inferior vena cava (dIVC), and haemodynamic parameters, including the CVP, were collected. RESULTS: Seventy-four patients were included. Thirty-one were included in the low LVEF (< 55%) group, and 43 were included in the high LVEF (≥55%) group. In the high LVEF group, the TAPSE and CVP were not correlated (r = - 0.234, P = 0.151). In the low LVEF group, partial correlation analysis indicated that the TAPSE and CVP were correlated (r = - 0.516, P = 0.006), and multivariable linear regression analysis indicated that the TAPSE was independently associated with the CVP (standard coefficient: - 0.601, p < 0.001). Additionally, in the low LVEF group, a ROC analysis showed that the area under the curve of the TAPSE for the detection of CVP greater than 8 mmHg was 0.860 (95% confidence interval: 0.730-0.991; P = 0.001). The optimum cut-off value was 1.52 cm, which resulted in a sensitivity of 75.0%, a specificity of 86.7%, a positive predictive value of 84.6% and a negative predictive value of 77.8%. CONCLUSIONS: The TAPSE is inversely correlated with the CVP in mechanically ventilated critically ill patients who have a LVEF less than 55%.

Different effects of cardiac and diaphragm function assessed by ultrasound on extubation outcomes in difficult-to-wean patients: a cohort study.

BACKGROUND: Ultrasound is a convenient tool to evaluate cardiac and diaphragm function. The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue Doppler wave velocity by transthoracic echocardiography (TTE) and diaphragmatic excursion (DE) by diaphragm ultrasound have been confirmed in predicting extubation outcomes independently, however their different roles in the weaning process have not been determined until now. METHODS: We designed a cohort study to preform diaphragm ultrasound and TTE before and after the spontaneous breathing trial (SBT) in difficult-to-wean patients. Patients considered for enrollment should succeed on a SBT and have been extubated. They were followed up with the events of respiratory failure within 48 h, and divided into the respiratory failure and extubation success subgroups. Relevant risk factors predicting respiratory failure were analysed by a multivariate logistic regression model. Then, each subgroup was assessed with respect to re-intubation within 1 week, and divided into the re-intubation and non-intubation subgroups. Furthermore, relevant risk factors predicting re-intubation were also analysed in each subgroup. The area under the curve (AUC) and optimum cut-off value were identified by the receiver operating characteristic curve. RESULTS: Among 60 patients, 29 cases developed respiratory failure within 48 h, and 14 cases were re-intubated or died within 1 week, respectively. Multivariate logistic regression analysis showed that E/Ea (average) after SBT [odds ratio (OR) 1.450, 95% confidence intervals (CI) 1.092-1.926, P = 0.01] and left ventricular ejection fraction were associated with respiratory failure. The AUC of E/Ea (average) after SBT was 0.789, and a cut-off value ≥ 12.5 showed the highest diagnostic accuracy with a sensitivity and specificity of 72.4% and 77.4%, respectively. Furthermore, in the respiratory failure subgroup only DE (average) after SBT was associated with re-intubation (OR 0.690, CI 0.499-0.953, P = 0.024). The AUC of DE (average) after SBT was 0.805, and a cut-off value ≤ 12.6 mm showed the highest diagnostic accuracy with a sensitivity and specificity of 80% and 68.4%, respectively. CONCLUSIONS: E/Ea (average) after SBT could help predict respiratory failure within 48 h. However, DE (average) after SBT could help predict re-intubation within 1 week in the respiratory failure subgroup.

[Variations of renal vascular score and resistive indices in septic shock patients].

OBJECTIVE: To assess the variations of renal vascularization scale and resistive index in septic shock patients during the first 6 h in intensive care unit (ICU). METHODS: A total of 39 septic shock patients were prospectively enrolled to receive echocardiographic and renal ultrasound examinations. And the data of mean arterial pressure (MAP), central venous pressure (CVP), cardiac output (CO), renal vascularization scale (VS) and resistive index (RI) were recorded. RESULTS: Among 19 patients without an increase of CVP, 8 of them showed significant increase in MAP and CO. Six of 8 patients with increases both in MAP and CO displayed an increase of VS while only 1 out of the remaining 11 patients had an increase of VS (P = 0.027). Among 20 patients with an increase of CVP, 9 of them showed no significant increase in MAP or CO. Eight out of 9 patients without significant increase in MAP or CO displayed a decrease of VS while only 2 out of the remaining 11 patients displayed a decrease of VS (P = 0.086). They were divided into two groups according to the variations of MAP, CVP and CO respectively. No significant change of RI was found between oh and 6 h in each group. CONCLUSION: The renal vascularization scale increases in patients with increases both in CO and MAP while CVP remains almost unchanged. No significant relationship exists between resistive index and such hemodynamic parameters as CO, MAP and CVP.

Melatonin improved rat cardiac mitochondria and survival rate in septic heart injury.

The pathogenesis of septic myocardial depression is complicated. Mitochondrial dysfunction has been suggested to be one of the main reasons for the reduced cardiac function. As melatonin is an antioxidant with the potential to scavenge radicals in mitochondria, we therefore employed a sepsis model, that is, cecal ligation and double puncture (CLP) in rats, to study the melatonin effects on: (i), myocardial mitochondrial function; (ii), heart systolic function; and (iii), prognosis of septic rats. We demonstrate that melatonin treatment (30 mg/kg, 3, 6, 12, 18, 24 hr after CLP) (i) improved myocardial cytochrome c oxidase (CcOX) activity and blood lactate level, (ii) attenuated heart dysfunction with a higher left ventricular ejection fraction (EF), and (iii) promoted 48-h survival of the rats compared to CLP animals with no melatonin treatment. In conclusion, our results show that rat myocardial mitochondrial CcOX activity was depressed during severe sepsis accompanied by myocardial depression characterized by the decline of EF. In septic rats, melatonin increased the CcOX activity, improved heart systolic function, and lowered mortality rate. The clinical use of melatonin in septic myocardial depression should be tested in the future.

[Value of dynamic arterial elastance in the predication of arterial pressure response to volume loading in shock patients].

OBJECTIVE: To explore the value of dynamic arterial elastance (Eadyn) in the predication of arterial pressure response to volume loading in shock patients. METHODS: A total of 32 patients with pulse indicator continuous cardiac output (PICCO) monitoring at our intensive care unit from January 2011 to December 2012 were retrospectively studied. The decision of fluid replacement was based upon the presence of shock (mean arterial pressure (MAP) ≤ 65 mm Hg, systolic arterial pressure <90 mm Hg or a decrease of 40 mm Hg from baseline) and preserved volume responsiveness condition with a stroke volume variation (SVV) value ≥ 10%. According to the MAP increase after volume loading, they were classified into MAP responders (≥ 15%) and MAP nonresponders (<15%) respectively. The goal was to investigate the influencing factors of the changes of MAP after volume loading and predict the arterial pressure response to volume loading. RESULTS: Significantly different between MAP responders and MAP nonresponders, baseline Eadyn was an effective predictor of MAP increase after volume loading. The area under the ROC curve was 0.95 for the prediction of volume loading on MAP for Eadyn at baseline (P < 0.01). A baseline Eadyn value >0.85 predicted a MAP increase after volume administration with a sensitivity of 89.5% and a specificity of 92.3%. CONCLUSION: Baseline Eadyn may predict accurately arterial pressure response in MAP to volume loading in shock patients.

[Effects of early goal-directed diuresis therapy on the outcomes of critical ill patients].

OBJECTIVE: To evaluate the effects of early goal-directed diuresis therapy on the outcomes of critical ill patients. METHODS: A total of 56 critical patients enrolled received an injection of furosemide 5-40 mg under a precondition of stable hemodynamics. They were divided into two groups:standard group [Central venous pressure (CVP) decreased below 8 mm Hg] (n = 30) and control group (if not) (n = 26) depending on the goal of CVP.And the differences of survival rate, intensive care unit (ICU) days and ventilation days after diuresis therapy were compared between two groups. RESULTS: The survival rate of standard group was significantly higher than that of control group (96.7% vs 84.6%, P < 0.05) while the ICU days (4.4 ± 3.6 days) and ventilation days (1.2 ± 1.1 days) after diuresis therapy of standard group were significantly shorter than that of control group (12.5 ± 11.7 and 9.8 ± 9.6 days, P < 0.05). CONCLUSION: Early goal-directed diuresis therapy can improve the prognosis of critical ill patients.

[Clinical role of evaluating vascular paralysis in septic shock patients].

OBJECTIVE: To explore the effects of vascular paralysis upon prognosis and tissue perfusion in septic shock patients. METHODS: A total of 73 septic shock patients consecutively admitted into our department from January 2010 to July 2011 were retrospectively studied. Their hemodynamic data, arterial lactate concentration and APACHEII (acute physiology & chronic health evaluation II) score at the beginning of cardiac output monitoring (0h), as well as the outcome of Day 28 post-diagnosis were recorded. Stroke volume index (SVI) and cardiac index (CI) were obtained through transpulmonary thermodilution technique by pulse induced continuous cardiac output (PiCCO) system. RESULTS: (1) APACHEII score at 0h was higher in non-survivors than those in survivors ((14.6 ± 5.6) vs (20.4 ± 4.8), P < 0.01). Stroke systemic vascular resistance index (SSVRI), pulse pressure/stroke volume index (PP/SVI), effective arterial elastance index (EaI), 24h lactate clearance rate (24rLac) , 72h lactate clearance rate (72rLac) and 7d lactate clearance rate (7rLac) in non-survivors were all lower than those in survivors (P < 0.05); (2) SVRI, SSVRI, PP/SVI and EaI were all correlated significantly with 24rLac, 72rLac and 7rLac [ (212.7 ± 52.6) vs (185.4 ± 50.5) , PP/SVI: (2.8 ± 0.7) vs (2.5 ± 0.6), EaI: (5.0 ± 1.2) vs (4.3 ± 1.1), 24/72/7 rLac: (18.4 ± 46.4) vs (21.5 ± 49.7), (19.9 ± 49.6) vs (-21.5 ± 46.3), (35.5 ± 45.8) vs (-59.5 ± 64.5), P < 0.00]. CONCLUSION: Vascular paralysis is correlated with prognosis and tissue perfusion in septic shock patients. And SSVRI, PP/SVI and EaI are more significant.

[Variations of left ventricular-arterial coupling in septic shock].

OBJECTIVE: To explore the variations of left ventricular-arterial coupling and elucidate its mechanisms in septic shock. METHODS: Septic shock rabbits were established by an intravenous injection of endotoxin. A total of 12 rabbits were divided randomly into sham operation group (S, n = 6) and endotoxin injection group (E, n = 6). Ultrasonic echocardiography and hemodynamic monitoring were conducted at 0h (30-min post-operation), 2h (1-hour after endotoxin or saline injection) and 4h (3-hour after endotoxin or saline injection) and the relative hemodynamic indices were recorded. RESULTS: (1) In E group, end-systolic elastance (Ees) at 2h was lower than that at 0h (75.72 ± 5.16 vs 90.77 ± 7.17 mm Hg/ml) and Ees at 4h was lower than that at 2h (58.45 ± 3.63 vs 75.72 ± 5.16 mm Hg/ml, P < 0.05); (2) In E group, left ventricular diastolic volume (LVDV) at 2h and 4h were both lower than that at 0h (3.26 ± 0.21 vs 3.58 ± 0.25 ml, 3.27 ± 0.19 vs 3.58 ± 0.25 ml). And left ventricular end diastolic compliance (Ced) at 4h were lower than that at 0h and 2h (0.61 ± 0.05 vs 0.74 ± 0.07 ml/mm Hg, 0.61 ± 0.05 vs 0.75 ± 0.08 ml/mm Hg, P < 0.05); (3) In E group, Ea at 2h and 4h was lower than that at 0h (41.35 ± 2.87 vs 50.46 ± 3.22 mm Hg/ml, 40.13 ± 2.68 vs 50.46 ± 3.22 mm Hg/ml, P < 0.05); (4) In E group, Ea/Ees at 4h was higher than that at 0h and 4h (0.70 ± 0.07 vs 0.57 ± 0.06, 0.70 ± 0.07 vs 0.56 ± 0.05, P < 0.05). And Ea/Ees at 2h had no significant difference with that at 0h (0.56 ± 0.05 vs 0.57 ± 0.06, P < 0.05). CONCLUSION: During compensatory stage of septic shock, left ventricular-arterial coupling shows no significant variation. However, during decompensatory stage of septic shock, there is significant left ventricular-arterial decoupling. The main reason for decoupling lies in that the decrease of left myocardial contractility is more significant than that of left ventricular afterload. And ventricular diastolic dysfunction may also participate.

Effect of Glucose Contents on Electrochemical Corrosion Behavior of Ti/ZrO2 Brazing Joint in SBF.

The effect of glucose content on the electrochemical corrosion behavior of the Ti/ZrO2 brazing joint in simulated body fluid (SBF) was researched by the means of SEM morphologies, electrochemical and XPS analyses. Herein, pitting is observed to be a dominating corrosion model under the investigated glucose content. The pitting corrosion of the joint in 200 mg/dL SBF is minimal. In addition, the joint in 200 mg/dL SBF manifests the best corrosion resistance by electrochemical analyses, which indicates that glucose content has a bidirectional effect on corrosion of the Ti/ZrO2 brazing joint. Additionally, the corrosion current value and impedance of titanium and brazing joint are close, which indicates that their corrosion resistance is similar. Finally, the OH-, Cl-, Sn2+/Sn4+ and -COOH on the joint surface are found by XPS analysis, and the mechanism of Ti/ZrO2 brazing joint corrosion is elucidated. The study provides a novel understanding of the corrosion behavior and relevant corrosion mechanism of the Ti/ZrO2 brazing joint in body fluids with different glucose content.

Prognostic implication of a novel right ventricular injury score in septic patients.

AIMS: We aim to investigate the prognostic value of a right ventricular (RV) injury score based on the concept of RV dilation, RV systolic dysfunction, and RV-pulmonary arterial (PA) decoupling in septic patients and to explore whether the RV injury (RVI) score can be used to grade the severity of RV dysfunction in these patients. METHODS AND RESULTS: Septic patients admitted to the ICU were prospectively included. We collected haemodynamic and echocardiographic parameters as well as prognostic information. RV dilation was defined as right and left ventricular end-diastolic area ratio (R/LVEDA) > 2/3. RVSD was defined as tricuspid annular plane systolic excursion (TAPSE) < 17 mm, right ventricular fractional area change (FAC) < 35%, or peak velocity of tricuspid annulus via tissue Doppler (S') < 10 cm/s. RV-PA decoupling was represented by the TAPSE/pulmonary arterial systolic pressure (PASP) ratio. RVI score were determined by the presence of the following findings: RVSD, RV dilation, and RV-PA decoupling, that is, one point for each finding. A total of 327 patients were enrolled in this study, among whom 276 survived and 51 died at 30 days after admission. Overall, 18.0% had RV dilation, 35.8% had RVSD, and 21.4% had RV-PA decoupling, with an appreciable overlap present. A multivariate Cox regression analysis showed that RV dilation (HR: 2.19, 95% CI: 1.19-4.01, P = 0.011), RVSD (HR: 2.25, 95% CI: 1.23-4.13, P = 0.009) and RV-PA decoupling (HR: 2.08, 95% CI: 1.19-3.65, P = 0.011) were independently associated with a 30 day mortality. Furthermore, RVI score was also an independent predictor, displayed additive effect with respect to 30 day mortality (RVI score 1 vs. RVI score 0, HR: 2.94, 95% CI: 1.20-7.20, P = 0.018; RVI score 2 vs. RVI score 0, HR: 3.20, 95% CI: 1.28-7.98, P = 0.013; RVI score 3 vs. RVI score 0, HR: 7.17, 95% CI: 2.65-19.38, P < 0.001), and had the best performance in model goodness of fit, discrimination and variance explained than the other RV indices. CONCLUSIONS: The RVI score was independently related to 30 day mortality and had the potential to grade the severity of RV dysfunction in septic patients.

Thiol catalyzed formation of NO-ferroheme regulates canonical intravascular NO signaling.

Nitric oxide (NO) is an endogenously produced physiological signaling molecule that regulates blood flow and platelet activation. However, both the intracellular and intravascular diffusion of NO is severely limited by scavenging reactions with hemoglobin, myoglobin, and other hemoproteins, raising unanswered questions as to how free NO can signal in hemoprotein-rich environments, like blood and cardiomyocytes. We explored the hypothesis that NO could be stabilized as a ferrous heme-nitrosyl complex (Fe 2+ -NO, NO-ferroheme) either in solution within membranes or bound to albumin. Unexpectedly, we observed a rapid reaction of NO with free ferric heme (Fe 3+ ) and a reduced thiol under physiological conditions to yield NO-ferroheme and a thiyl radical. This thiol-catalyzed reductive nitrosylation reaction occurs readily when the hemin is solubilized in lipophilic environments, such as red blood cell membranes, or bound to serum albumin. NO-ferroheme albumin is stable, even in the presence of excess oxyhemoglobin, and potently inhibits platelet activation. NO-ferroheme-albumin administered intravenously to mice dose-dependently vasodilates at low- to mid-nanomolar concentrations. In conclusion, we report the fastest rate of reductive nitrosylation observed to date to generate a NO-ferroheme molecule that resists oxidative inactivation, is soluble in cell membranes, and is transported intravascularly by albumin to promote potent vasodilation.

[Value of power Doppler ultrasound to evaluate acute kidney injury].

OBJECTIVE: To explore the value of power Doppler ultrasound (PDU) in the evaluation of acute kidney injury(AKI). METHODS: Renal blood flow of 40 AKI cases was monitored by power Doppler ultrasound and 4-level semiquantitative PDU score method employed. All cases were divided into 3 groups by PDU score. AKI stage and duration were compared. And the co-variables of death and (continuous renal replacement therapy) CRRT days (> 3) were also analyzed by Logistic regression analysis. RESULTS: A total of 40 AKI case were recruited. The 3-score group (n = 13)has lower mortality in intensive care unit and at 28 days than the 2-score group (n = 15) and the 1-score group (n = 12). The number of stage-3 AKI in the 3-score group was less than that in the 2-score and 1-score groups (n = 1, 4, 9 correspondingly, χ(2) = 16.103, degree of freedom = 4, P = 0.003). The number of persistent AKI in the 3-score group was less than that in the 2-score and 1-score groups (n = 3, 9, 10 correspondingly, P < 0.05). Age, APACHEII score and PDU score (< 3) were closely correlated with death while age, APACHEII score, level of serum creatinine and PDU score (< 3) with CRRT days (> 3) (P < 0.05). CONCLUSION: PDU may be used to monitor renal hemodynamics in AKI patients and its score helps clinicians to evaluate the severity and prognosis of AKI.

[Left ventricular-arterial coupling in the resuscitation of refractory septic shock].

OBJECTIVE: To explore the role of left ventricular-arterial coupling in the resuscitation of refractory septic shock. METHODS: A total of 58 patients with refractory septic shock admitted from January 2010 to July 2011 were retrospectively studied. Hemodynamic data, arterial lactate concentration and APACHEII (acute physiology & chronic health evaluation II) score at the beginning of and 24 hours after cardiac output monitoring, as well as the outcome of Day 28 post-diagnosis were recorded. Stroke volume index (SVI), cardiac index (CI) and global end diastolic volume index (GEDVI) were obtained through transpulmonary thermodilution technique by a pulse induced continuous cardiac output (PiCCO) system. Left ventricular end systolic volume index (LVESVI) was approximated to (GEDVI/4-SVI) while effective arterial elastance index/ventricular end systolic elastance index (EaI/EesI) was approximated to LVESVI/SVI. RESULTS: (1) APACHEII score at the 24th hour, 24 hs lactate clearance rate and 24 hs Ea/Ees variation (ΔEa/Ees) were higher in non-survivors than those in survivors; (2) binary Logistic regression analysis showed that ΔEa/Ees and APACHEII score at the 24th hour were the independent risk factors of mortality for refractory septic shock. And the OR value of ΔEa/Ees was higher than that of APACHEII score (2.04 vs 1.63). Their areas of ROC curve were 0.705 (95%CI 0.569 - 0.841, P = 0.007) and 0.939 (95%CI 0.878 - 1.000, P = 0.000) respectively; (3) all hemodynamic parameters at the beginning had no difference between ΔEa/Ees > 0 and ΔEa/Ees ≤ 0 groups. CI, SVI, EGDT (early goal-directed therapy) compliance rate at the 24th hour in the ΔEa/Ees > 0 group were lower than those in the ΔEa/Ees ≤ 0 group. The effective arterial elastance index (EaI) at the 24th hour and the mortality rate of Day 28 in the ΔEa/Ees > 0 group were higher than those in the ΔEa/Ees ≤ 0 group; (4) during the 24 hs treatment, ΔEa/Ees was correlated negatively with the variations of CI, SVI, EesI and lactate clearance rate and positively with the variations of heart rate, GEDVI, systolic vascular resistance index and EaI. CONCLUSION: ΔEa/Ees may be used as an excellent marker of predicting the outcome of refractory septic shock. Lowing Ea/Ees in resuscitation has beneficial effects on EGDT compliance, lactate clearance and outcome.