Objective:To investigate the efficacy and safety of different dosage regimens of levosimendan in elderly patients with severe heart failure.Methods:Thirty-two patients 75 years or older were randomly divided into a loading dose group (16 cases) in which levosimendan was maintained at 0.1 μg·kg -1·min -1 for 24 h after loaded with 6 μg/kg, and a maintenance dose group (16 cases) with same schedule without loading dose. The amino-terminal brain natriuretic peptide (NT-proBNP) before and after treatment was detected. Left ventricular ejection fraction (LVEF), stroke volume (SV), stroke volume index (SVI) by echocardiograph were monitored. Adverse events, the length of stay in ICU and 28-day mortality were recorded. Results:The NT-proBNP level in loading group after treatment was 1 950 (922,6 481)ng/L, which was improved than that before treatment [4 018(2 716,9 637)ng/L, P<0.05]. The result was similar in maintenance group [1 390 (599,3 297)ng/L vs. 4 576 (2 681,10 682)ng/L, P<0.05]. LVEF in loading group before and after treatment was (39.4±8.8) % vs. (48.9±9.2) % respectively, while in maintenance group it was (40.4±8.8) % vs. (48.7±12.0) % (both P<0.05). SV were also improved after treatment in both groups compared with baseline levels ( P<0.05). NT-proBNP started to decline on day 3 in the loading group, while on day 7 in the maintenance group. SVI recovered on day 14 in the loading group [ (29.4±6.5) ml/m 2 vs. (27.3±6.7) ml/m 2, P<0.05], while it did not change much in the maintenance group. There was no significant differences as to the length of stay in ICU [ (11.1±4.4) d in loading group vs. (9.6±3.5) d in maintenance group] and 28-day mortality rates were comparable (2/16 in loading group vs. 1/16 in maintenance group) . The adverse events were 7 vs. 2 cases in loading group and maintenance group respectively, which were mild and all alleviated. Conclusion:The application of levosimendan only with maintenance dose improves cardiac function in very elderly patients with severe heart failure. Adverse events are mild and manageable.

Objective:To investigate the value of programmed death-1（PD-1） expression on the T lymphocytes for the prognosis of septic patients.Methods:From September 2017 to May 2019, septic patients were included in Department of Intensive Care Unit at 6 hospitals. The PD-1 expression on T cells were measured by flow cytometry. Logistic regression was conducted to analyze independent risk factors related to death within 28 days，and receiver operating characteristic curve(ROC) was conducted to evaluate the prognostic value of PD-1 expression on T cells in septic patients.Results:A total of 64 septic patients were enrolled to this study，including 32 survivors and 32 deaths. The PD-1 expression on T cells in the death group was significantly higher than that in the surviving group ( P<0.05). Correlation analysis showed that the percentages of PD-1 +/CD3 +T cells and PD-1 +/CD8 +T cells were positively correlated with procalciton in ( r=0.313, P =0.015； r=0.375, P=0.003), logistic regression analysis showed that the percentages of PD-1 +/CD3 +，PD-1 +/CD4 +，PD-1 +/CD8 +T cells were independent risk factors for the death of sepsis patients. The percentage of PD-1 +/CD3 +T cell was 3.63%, with AUC 0.842, sensitivity to predict the mortality 96.43% and specificity 59.38%, ( P<0.000 1). The percentage of PD-1 +/CD4 +T cell was 4.65%, with AUC 0.847, sensitivity 96.43%, specificity 62.50%，( P<0.000 1). The percentage of PD-1 +/CD8 +T cell was 3.91%, with AUC 0.771, sensitivity 64.29%, specificity 81.25%，( P=0.000 3). Conclusions:The T cell PD-1 expression is an independent risk factor to predict the 28-day mortality in septic patients. Combining the proportions of PD-1 +/CD3 +, PD-1 +/CD4 +and PD-1 +/CD8 +T cells may further enhance the predictive value for death.

Objective To investigate the effect of levosimendan on cardiac function and prognosis in elderly patients with septic myocardial contractility impairment.Methods A prospective,randomized,controlled study was conducted.The elderly patients with septic myocardial contractility impairment who were admitted to Intensive Care Unit in Zhejiang Hospital were consecutively enrolled from January 2017 to September 2017.The key inclusive criterion was left ventricular ejection fraction (LVEF) ≤ 50％ after fluid resuscitation.A total of 30 patients were randomly assigned to levosimendan group (n=15) and dobutamine group (n=15).Based onconventional treatment,intravenous dobutamine (5 μg per kilogram of body weight per minute) or levosimendan (0.2 μg per kilogram of body weight per minute)were continuously administrated for 24 hours in two groups.At 0 h,24 h,48 h,72 h after injection,the following parameters or values were recorded including serum lactic acid (Lac),and echocardiographic parameters such as LVEF,stroke volume (SV).The time of mechanical ventilation,length of stay in ICU and 28-day mortality were compared in two groups.Results Compared with dobutamine group,blood Lac at 24 h [(1.97±1.10)mmol/L vs.(2.73 ± 2.06) mmol/L,P=0.002] decreased significantlyin levosimendan group.LVEF and SV were significantly higher in levosimendan group at 24 h [LVEF:(47.93±5.01)％ vs.(45.60±5.47)％,P=0.004;SV:(47.73 ± 14.01) ml vs.(44.80±16.89) ml,P=0.035;respectively],48 h [LVEF:(51.07 ± 5.05)％ vs.(46.73 ± 6.34)％,P=0.004;SV:(49.87 ± 14.15) ml vs.(45.07± 16.94) ml,P=0.005;respectively] and 72 h [LVEF:(53.20±5.92)％ vs.(47.70±6.71)％,P=0.002;SV:(51.27±14.98) ml vs.(45.73±17.34) ml,P=0.010].The time of mechanical ventilation,length of stay in ICU and 28-day mortality were comparable between two groups (P＞0.05).Conclusions Levosimendan improves cardiac systolic function and tissue perfusion in elderly patients with septic myocardial contractility impairment.However,cardiac diastolic function,liver and kidney function are not further improved by levosimendan compare with dubutamine.Time of mechanical ventilation,length of stay in ICU and 28-day mortality in two groups are similar.

To analyze the correlation between transcutaneous oxygen pressure (PtcO2) and blood lactate in patients with septic shock. Fifty-sixpatients with septic shock were prospectively investigated. PtcO2 was monitored continuously for 6 hours, and arterial blood gas was measured at baseline (T0) and 6 hours (T6). Records of PtcO2, were analyzed for the correlation with lactate level and lactate clearance rate. PtcO2 valuesin the high lactate clearance group and the low one were compared.The lowest value of PtcO2 at T6 and duration of PtcO2<40 mmHg (1 mmHg=0.133 kPa) were both correlated with lactate level and lactate clearance rateat T6. The low predictive value of PtcO2 was 29 mmHg of lactate clearance under 20％with a sensitivity 85.2％and a specificity 65.5％. The low predictive value of PtcO2 in high lactate clearance group was significantly higher than that in low lactate clearance group, while the duration of PtcO2<40 mmHg was shorter than the latter. During 6 h continuous monitoring, patients with a significant low PtcO2 or prolonged duration of low PtcO2 have relatively high lactate or low lactate clearance after resuscitation.

Objective To investigate the influence of left ventricular-arterial coupling(VAC) on clinical prognosis of elderly patients with septic shock.Methods A total of 56 elderly septic shoek patients were enrolled in this study,all of whom were admitted to Department of Intensive Care Unit in Zhejiang Hospital from August 2014 to October 2015.The patients were divided into two groups according to the status of left ventricular-arterial coupling when septic shock was diagnosed,which were left ventricular-arterial uncoupling group(UC group) and left ventricular-arterial coupling group(C group).Various parameters were recorded,including blood lactate level,central venous oxygen saturation(ScvO2),serum level of N-terminal pro-brain natriuretic peptide(NT-proBNP) and cardiac troponin Ⅰ (cTN Ⅰ),dose of vasoactive drugs,the total fluid volume and urine volume per hour within 24 hours.The 28-day survival rate was a key index of prognosis.Multivariate logistic regression was taken to analyze risk factors related to death within 28 day.Results Compared with C group,UC group had lower values of left ventricular ejection fraction[(42.43 ±4.76)％ vs (53.17±3.01)％;P＜0.01] and cardiac index[(2.36±0.68) L· min-1 · m 2vs (2.93±0.45)L · min-1 · m-2;P ＜0.01].Yet serum levels of NT-proBNP[lg NT-proBNP 3.93 ±0.53 vs 3.40 ±0.63;P =0.004] and cTN Ⅰ [lg cTN Ⅰ-0.16 ± 0.68 vs-1.03 ± 0.69;P ＜ 0.001] in UC group were higher than those in C group.Moreover,the total fluid volume within 24 hours [(3 806.3 ± 831.4) ml vs (3 142.0±770.0) ml;P =0.016],blood lactate level[(5.61 ±2.68) mmol/L vs (3.93 ± 1.59)mmol/L;P =0.043] and dose of norepinephrine[(0.630 ±0.300) μg · kg-1 · min-1 vs (0.292 ±0.234)μg · kg-1 · min-1;P =0.001] in UC group were greater than those in C group,while ScvO2 [(60.75 ±2.91)％ vs (64.42 ±2.19)％;P＜0.001] and urine volume per hour[(0.518 ±0.358) ml vs (0.926 ±0.678) ml;P =0.007] were less than those in C group.Compared with C group,UC group had a lower 28-day survival rate [43.2％ (19/44) vs 9/12;P =0.049].Ea/Ees ratio was negatively correlated with LVEF,ScvO2 (r =-0.686,P ＜ 0.001;r =-0.411,P =0.002),positively correlated with NT-proBNP,cTN Ⅰ (r =0.294,P =0.028;r =0.363,P =0.006),yet no obvious correlation was noticed with blood lactate level (r =0.170,P =0.21).Multiple logistic regression analysis showed that VAC(OR =11.187,95％ CI 2.489-50.285;P =0.002),lactate level (OR =1.727,95 ％ CI 1.164-2.563;P =0.007) and lg cTN Ⅰ (OR =0.247,95 ％ CI 0.079-0.779;P =0.017) were independent risk factors affecting 28-day mortality.Conclutions In elderly patients with septic shock,left ventricular-arterial uncoupling indicates a lower 28-day survival rate,worse cardiac function and tissue perfusion.Ea/Ees ratio might sever as a predictive indicator of 28-day mortality.

BACKGROUNDSevere sepsis and septic shock are the leading causes of morbidity and mortality in hospitalized patients. This study aimed to investigate the association of poly (ADP-ribose) polymerase-1 (PARP-1) activity in circulating mononuclear cells with myocardial dysfunction in patients with septic shock.

METHODSA total of 64 patients with septic shock were divided into the survival group (n = 41) and the nonsurvival group (n = 23) according to mortality at 28 days after enrollments. PARP-1 activity in circulating mononuclear cells, brain natriuretic peptide, Acute Physiology and Chronic Health Evaluation II score, the cardiac index (CI), the cardiac function index (CFI), global ejection fraction (GEF), and the left ventricular contractility index (dp/dt max) were measured after admission to the intensive care unit.

RESULTSPARP-1 activity in circulating mononuclear cells of nonsurvival patients with septic shock was significantly higher than that in survival patients. PARP-1 activity in circulating mononuclear cells was strongly, negatively correlated with the CI, the CFI, GEF, and dp/dt max. Multiple Logistic regression analysis showed that PARP-1 activity in circulating mononuclear cells was an independent risk factor of myocardial dysfunction. The optimal cutoff point of PARP-1 activity for predicting 28-day mortality was 942 nmol/L with a sensibility of 78.2% and specificity of 65.1%.

CONCLUSIONPARP-1 activity in circulating mononuclear cells is significantly associated with myocardial dysfunction and may have prognostic value in patients with septic shock.

Aged ; Aged, 80 and over ; Female ; Humans ; Leukocytes, Mononuclear ; enzymology ; Male ; Middle Aged ; Poly(ADP-ribose) Polymerases ; metabolism ; Shock, Septic ; enzymology

Objective To investigate the association between body mass index (BMI) and exercise capacity in patients with chronic systolic heart failure.Methods The elderly patients with chronic systolic heart failure were consecutively recruited from 2008 to 2011 in cardiovascular clinic of Zhejiang Hospital.All the participants underwent height and weight measurements and BMI was calculated with these two parameters.Cardiopulmonary exercise test were performed to achieve peak oxygen uptake (PVO2),oxygen uptake to body mass ratio (PKVO2),oxygen uptake to heart ratio (VO2/HR) and ventilation/carbon dioxide production (VO2/VCO2).Results A total of the 273 patients with chronic systolic heart failure included 6 underweight patients (BMI ＜ 18.5 kg/m2),113 normal weight patients (BMI 18.5-＜ 24.0 kg/m2),116 overweight patients (BMI 24.0-＜ 28.0 kg/m2),and 38 obese patients (BMI ≥ 28 kg/m2).In both NYHA Ⅱ and Ⅲ/Ⅳ patients,unadjusted correlation analyses showed that BMI was positively related to PVO2 and VO2/HR,and was inversely related to PKVO2 and VE/VCO2 (P ＜ 0.05),respectively.Multiple stepwise regression analyses showed age,sex,BMI (P ＜ 0.05) and left ventricular ejection fraction (LVEF) were independent determinants of PKVO2,and age and BMI (P ＜ 0.05) were independent determinants of VE/VCO2.Conclusions BMI is significantly associated with exercise capacity in patients with chronic systolic heart failure,and also independent determinant for the PKVO2 and VE/VCO2,respectively.

Objective To investigate the role of damaged mitochondria in cardiac cell apoptosis in septic rats and the possible mechanism involved.Methods Seventy-two Sprague-Dawley rats were randomly (random number) divided into negative control group (n =18) and septic group (further divided into three groups as per rats sacrificed 6 h,12 h,and 24 h after endotoxin injection intra-peritoneally,n =18).The hearts of rats were taken.The changes of cardiac morphology were observed under light microscope and scanning electron microscope.Cell apoptosis in situ were examined by using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B (NF-κB) activation in myocardium was detected by using Western blotting to estimate myocardial cell apoptosis.Mitochondrial lipid and protein oxidation were measured to assess oxidative stress,and mitochondrial superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined to estimate antioxidant defense.Results Septic induced inflammatory cells infiltration,myocardium degeneration and effusion in a time-dependent manner.A remarkable expansion of capillaries could be observed in the hearts of infected rats at post-challenge of 24 h.Compared with sham-treated rats,the percentage of apoptosis increased in a time-dependent manner in the hearts of infected rats at 6 h,12 h,24 h of post-injection (P ＜0.05).The concentration of NF-κB p65 in the cytosol decreased gradually and increased in the nucleus during sepsis in a time-dependent manner (P ＜0.05),indicating that septic challenge provoked progressive activation of NF-κB.Mitochondrial cristae disappeared in 6 h of challenge,and significant mitochondrial cristae disappearance,vacuolization,and rupture of mitochondria membrane became markedly obvious 12 and 24 h later.Both SOD and GPx activities decreased,while mitochondrial lipid and protein oxidation increased in a time-dependent manner after 6-24 h of challenge (P ＜ 0.05).Conclusions Septic challenge induced myocardial apoptosis and mitochondrial damage.Further,damaged mitochondria might play an important role by means of alteration of defenses against reactive oxygen species in myocardial cell apoptosis during sepsis.

Objective To investigate the clinical values of central venous pressure (CVP) versus stroke volume variation (SVV) in patients with severe sepsis after early goal-directed therapy (EGDT).Methods Totally 30 mechanically ventilated patients with severe sepsis who underwent goal-achieved EGDT were enrolled and randomly divided into CVP group (study group) and SVV group (control group) according to the data detected by pulse contour continuous cardiac output (PiCCO) analysis device.The differences in 28-day survival,3-day APACHE Ⅱ score,time of ICU stay,duration of mechanical ventilation,number that need CRRT,entral venous pressure (CVP),heart end-diastolic volume index (GEDVI),intrathoracic blood volume index (ITBVI),extravascular lung water index (EVLWI),cardiac index (CI),central venous oxygen saturation (ScvO2),lactate clearance rate and APACHE Ⅱ score were compared between the 2 groups.Results The death rate had no difference between the 2 groups(x2=0.240,P=0.624).Among survival patients in the CVP group,the time of ICU stay and duration of mechanical ventilation were shorter in study group than in control group(t=2.166,P=0.041;t=2.104,P=0.046),APACHE Ⅱ score at 3th day was decreased(t=2.20,P =0.038).The values of ITBVI,GEDVI,CI,lactate clearance rate were higher in study group than in control group (t=2.759,2.146,2.199,2.654,3.362,P=0.011,0.043,0.038,0.014,0.003).EVLWI and APACHE Ⅱ score were not different (P＞0.05) between the two groups.Conclusions SVV as a recovery target for fluid resuscitation can reach a better recovery results and improvement of prognosis than CVP goal-achieved EGDT.

In this paper, we propose the construction of a fifth-order Windkessel model, and give complete mathematical solutions for this model. Utilizing the diastolic pulse wave analytical methods, we derived the parameters of the mathematical model. The parameters were further applied to estimate arterial compliance, blood flow inertia, peripheral resistance and other indices. With simulation tools we assess the validity of the model, and built a simulation circuit with the model parameters R, C and L. The model parameters were obtained from the high-order Windkessel model. The stroke volume of left ventricle is employed as the input of the simulation circuit. At the end of the circuit, the responding signal was gained. And it in turn was compared with the measured pulse waveform. The results show that the fifth-order Windkessel model is superior to the third-order Windkessel model in the pulse wave fitting and stability, and thus better reflects the role of microvessles in the circulatory system.
Algorithms ; Blood Vessels ; physiology ; Compliance ; Computer Simulation ; Humans ; Microcirculation ; physiology ; Models, Cardiovascular ; Stroke Volume ; physiology