Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent im...Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent impairment of the intestinal barrier.Levosimendan,a novel inotropic agent,binds to cardiac troponin C to enhance calcium sensitivity,activates ATP-dependent potassium channels in cardiomyocytes and vascular smooth muscle cells,exerts positive inotropic and vasodilatory effects,and reduces free radical generation,thereby improving systemic hemodynamics including intestinal circulation.However,clinical evidence regarding its protective effects on the intestinal barrier in HF patients remains limited,and the underlying mechanisms require further clarification.This study aims to investigate whether levosimendan confers protective effects on the intestinal barrier in HF patients and to explore its potential mechanisms.Methods:Network pharmacology was first used to analyze potential mechanisms of levosimendan in treating intestinal barrier dysfunction among HF patients.A total of 62 hospitalized patients with acute exacerbation of HF with reduced ejection fraction(HFrEF)were enrolled based on echocardiographic left ventricular ejection fraction.According to clinical medication regimens,patients were assigned to a conventional treatment group(n=31)or a levosimendan treatment group(n=31).The conventional treatment group received standard anti-HF therapy,while the levosimendan treatment group received levosimendan in addition to standard therapy.Enzyme-linked immunosorbent assays were used to measure plasma levels and changes in the intestinal-barrier proteins zonulin,intestinal fatty acid binding protein(I-FABP),proinflammatory cytokines[interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α],anti-inflammatory cytokine IL-10,and N-terminal probrain natriuretic peptide(NT-proBNP).Improvements in cardiac function and gastrointestinal symptoms were evaluated using the Kansas City Cardiomyopathy Questionnaire(KCCQ)and the Gastrointestinal Symptom Rating Scale(GSRS).Results:Network pharmacology indicated that the effects of levosimendan on intestinal barrier dysfunction in HF patients may involve inflammation-related pathways such as IL-17 and TNF.Clinically,after treatment,zonulin decreased by 32.94 ng/mL in the levosimendan treatment group versus 15.05 ng/mL in the conventional treatment group(P<0.05).I-FABP decreased by 6.97 pg/mL in the levosimendan treatment group but increased by 35.16 pg/mL in the conventional treatment group(P<0.05).IL-6,IL-17,and TNF-αdecreased by 1.11 pg/mL,1.21 pg/mL,and 2.83 pg/mL,respectively,in the levosimendan treatment group,whereas they increased by 7.68 pg/mL,0.67 pg/mL,and 2.38 pg/mL in the conventional treatment group(all P<0.05).IL-10 decreased by 24.48 pg/mL in the conventional treatment group but increased by 24.98 pg/mL in the levosimendan treatment group(P<0.05).NT-proBNP increased by 7.35 pg/mL in the conventional treatment group but decreased by 4.73 pg/mL in the levosimendan treatment group(P<0.05).KCCQ scores increased by 0.36 in the conventional treatment group and 1.86 in the levosimendan treatment group,GSRS scores decreased by 1.00 in the conventional treatment group and 2.40 in the levosimendan treatment group,respectively,but the differences were not statistically significant(both P>0.05).Conclusion:Levosimendan not only improves HF and gastrointestinal symptoms in hospitalized patients with acute exacerbation of HFrEF but also reduces plasma intestinal barrier factor levels.These effects may be associated with decreased plasma proinflammatory cytokines and increased anti-inflammatory cytokines after treatment,potentially involving IL-17 and TNF signaling pathways.展开更多
Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1...Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1 was administered at a single dose of 6 μg·kg^-1 levosimendan by intravenous bolus injection within 10 min, and then followed by intravenous infusion for 4 h at a dose per minute of 0.05 μg·kg^-1·min^-1. Similarly, each subject in the group 2 （or group 3） was given by intravenous bolus injection at a dose of 12 μg·kg^-1 （or 18 μg·kg^-1） followed by an infusion at a dose of 0.10 μg·kg^-1·min^-1 （or 0.15 μg·kg^-1·min^-1） levosimendan. Blood samples were collected at 0 （prior to dosing）, 0.17, 0.5, 1, 2, 3, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8 and 10 h after administrations. Levosimendan concentrations in plasma were measured by LC-MS/MS method. The pharmacokinetic parameters were calculated using a software Drug and Statistic （version 2.0）. Results After administrations of levosimendan at various dose levels, the half-life （t1/2） values were 1.50 ± 0.35, 1.64 ± 0.25 and 1.54 ± 0.39 h; the maximal concentrations after injections （Co） were 9.54 ± 3.90, 15.95 ± 7.84 and 28.46 ± 10.74 ng·mL^-1; the areas under concentration-time （AUCo-t （t=7.8）） were 33.63± 9.34,54.39 ± 15.34 and 78.36 ± 23.74 ng ·mL^-1·h, respectively. Conclusion The C0 and A UC0-tvalues of levosimendan exhibited a dose-dependent manner, respectively. No differences in the pharmacokinetic parameters were observed between male and female Chinese subjects.展开更多
Objective: To evaluate the clinical efficacy of levosimendan versus dobutamine in critically ill patients requiring inotropic support. Methods: Clinical trials were searched in PubMed, EMBASE, and the Cochrane Central...Objective: To evaluate the clinical efficacy of levosimendan versus dobutamine in critically ill patients requiring inotropic support. Methods: Clinical trials were searched in PubMed, EMBASE, and the Cochrane Central Registry of Clinical Trials, as well as Web of Science. Studies were included if they compared levosimendan with dobutamine in critically ill patients requiring inotropic support, and provided at least one outcome of interest. Outcomes of interest included mortality, incidence of hypotension, supraventricular arrhythmias, and ventricular arrhythmias. Results: Data from a total of 3052 patients from 22 randomized controlled trials (RCTs) were included in the analysis. Overall analysis showed that the use of levosimendan was associated with a significant reduction in mortality (269 of 1373 [19.6%] in the levosimendan group, versus 328 of 1278 [25.7%] in the dobutamine group, risk ratio (RR)=0.81, 95% confidence interval (CI) 0.70-0.92, P for effect=0.002). Subgroup analysis indicated that the benefit from levosimendan could be found in the subpopulations of cardiac surgery, ischemic heart failure, and concomitant β-blocker therapy in comparison with dobutamine. There was no significant difference in the incidence of hypotension, supraventricular arrhythmias, or ventricular arrhythmias between the two drugs. Conclusions: In contrast with dobutamine, levosimendan is associated with a significant improvement in mortality in critically ill patients requiring inotropic support. Patients having cardiac surgery, with ischemic heart failure, and receiving concomitant β-blocker therapy may benefit from levosimendan. More RCTs are required to address the questions about no positive outcomes in the subpopulation in a cardiology setting, and to confirm the advantages in long-term prognosis.展开更多
OBJECTIVE:To investigate the clinical effects of Xinkeshu combined with levosimendan on perioperative heart failure in oldest-old patients with hip fractures.METHODS:Oldest-old patients over 80 years old with perioper...OBJECTIVE:To investigate the clinical effects of Xinkeshu combined with levosimendan on perioperative heart failure in oldest-old patients with hip fractures.METHODS:Oldest-old patients over 80 years old with perioperative heart failure and hip fractures were randomly divided into the control and observation groups,with 50 patients in each group.All patients in both groups were treated with conventional anti-heart failure therapy and levosimendan,whereas patients in the observation group additionally received Xinkeshu tablets.Clinical manifestations;left ventricular ejection fraction(LVEF);left ventricular end-diastolic dimension(LVEDD);left ventricular end-systolic dimension(LVESD);B-type natriuretic peptide(BNP),superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO),and endothelin-1(ET-1)levels;and self-rating anxiety scale(SAS)and self-rating depression scale(SDS)scores were compared between before and after treatment to evaluate the curative effects of Xinkeshu combined with levosimendan.RESULTS:After treatment,the efficacy rate was significantly higher in the observation group than in the control group.LVEF and the levels of SOD and NO were higher in the observation group than in the control group after treatment.However,LVEDD;LVESD;BNP,MDA,and ET-1 levels;and the SAS and SDS scores were lower after treatment in the observation group than in the control group.CONCLUSION:Levosimendan combined with Xinkeshu can improve cardiac function,alleviate oxidative stress,and relieve anxiety and depression in oldest-old patients with perioperative heart failure and hip fracture.展开更多
Background: Left ventricular ejection fraction is an independent determinant of the outcome of coronary artery bypass surgery. Low preoperative ejection fraction requires special care in terms of pharmacological and m...Background: Left ventricular ejection fraction is an independent determinant of the outcome of coronary artery bypass surgery. Low preoperative ejection fraction requires special care in terms of pharmacological and mechanical inotropic support. Adrenaline is the most widely used inotropic drug, while levosimendan is a relatively new inotropic drug in the field of cardiac surgery. In this study, we aimed to evaluate the relative efficacy of levosimendan in low ejection fraction patients undergoing coronary artery bypass grafting (CABG). Methods: A retrospective comparative study was performed with 63 patients who underwent isolated on-pump elective CABG with a preoperative ejection fraction below 40%. Patients were allocated to the adrenaline group (n = 35) and levosimendan group (n = 28). Patients were further stratified according to ejection fraction above 30% and below or equal to 30%. The primary outcome was cardiac-related mortality, while other parameters were considered secondary endpoints. Results: EuroSCORE of the adrenaline group was 3.34 ± 1.26 and for the levosimendan group 3.15 ± 1.42 (p value 0.576). Nine patients of the adrenaline group had new postoperative atrial fibrillation compared to seven patients in the levosimendan group (p value 0.948). Two patients of the adrenaline group had postoperative ventricular arrhythmia compared to only one patient in the other group (p value 0.691). The adrenaline group had higher doses of inotropic support compared to the levosimendan group 210.84 ± 23.74 and 157.4 ± 22.69 ng/kg/min respectively (p value Conclusions: The levosimendan-based protocol failed to improve overall mortality in low ejection fraction patients undergoing CABG. However, this protocol significantly reduced the dose of inotropic and vasoconstrictor support needed, ventilation hours and duration of ICU stay.展开更多
Aim: Increased oxidative stress plays important roles in vascular dysfunction in patients undergoing coronary artery bypass graft surgery. Hydrogen peroxide (H2O2) is used as an experimental model for oxidative stress...Aim: Increased oxidative stress plays important roles in vascular dysfunction in patients undergoing coronary artery bypass graft surgery. Hydrogen peroxide (H2O2) is used as an experimental model for oxidative stress. The present study was designed to assess the effects of levosimendan pretreatment on the contractile effects induced by H2O2 in human saphenous vein (HSV) segments. Methods: We studied H2O2 induced contractions of isolated HSV mounted in standard tissue baths. H2O2 (10-6 – 10-3 M) was added cumulatively to the organ bath. Concentration-response curves to H2O2 were repeated in the presence of levosimendan (10–8 M). In the second series of experiments, strips were contracted with 5-HT (10–5 M). When the contraction reached a stable plateau, H2O2 was administrated cumulatively into the organ bath. The same procedure was conducted in the presence of levosimendan. Results: Pretreatment of the SV strips with levosimendan significantly reduced the contractile response to each concentration of H2O2 . 5-HT produced contractions in SV strips. Further treatment of these strips with H2O2 resulted in statistically significant concentration-dependent increases in tension. Preincubation of the tissues with levosimendan did not significantly influence the maximum amplitude of the 5-HT-induced tone but inhibited the contractile effect of H2O2 on the 5-HT-induced contraction. Conclusion: Pretreatment of HSV with clinical concentrations of levosimendan inhibits the vasoconstriction caused by oxidative stress, indicating its potential preventive effect against oxidative stress induced graft spasm.展开更多
Introduction: In this study we explicated early results of patients (the patients in whom levosimendan was used) who underwent coronary artery bypass graft surgery with ejection fraction 35% or less. We compared this ...Introduction: In this study we explicated early results of patients (the patients in whom levosimendan was used) who underwent coronary artery bypass graft surgery with ejection fraction 35% or less. We compared this group with the patients in whom levo-simendan was not used. Material and Methods: 97 patients who have 35% ejection fraction or less taken to isolated coronary artery bypass surgery between January 2009 and December 2011 in our clinic are chosen for this study retrospectively. We compared the patients in whom levosimendan was used with the patients in whom levosimendan was not used. Levo- simendan (Simdax, Abbott) has been used according to surgeon’s decision in patients. Results: The mean age of group 1 was 62.3 ± 7.6, and the mean age of group 2 was 59.3 ± 10.5 (p > 0.05). It was detected that the average ejection fraction was less in group 1 (p 0.05). It was found that need for blood transfusion were less in group 1 than group 2 (p 0.05). Conclusion: We consider levosimendan reduces need for blood transfusion in coronary artery bypass graft surgery. This results may change with increasing number of patients so we consider that multicenter larger study is needed.展开更多
Objective:To investigate the effect of levosimendan on 28-day mortality in patients with sepsis.Methods:The English databases including Embase,PubMed,Web of Science,Cochrane Library and Chinese databasesincluding Chin...Objective:To investigate the effect of levosimendan on 28-day mortality in patients with sepsis.Methods:The English databases including Embase,PubMed,Web of Science,Cochrane Library and Chinese databasesincluding China National Knowledge Infrastructure(NKI),Wan fang Data,VIP,CBM were searched with levosimendan,sepsis and septic shock is as search terms.The published clinical randomized controlled trials of levosimendan injection were searched and the primary outcome measures of 28-day and 30-day mortality were included.Secondary outcome measures were left ventricular ejection fraction,left ventricular work index,cardiac index,and lactic acid.The literature retrieved is from the establishment of the database to October 2022.Stata 14.0 software was used for all data consolidation,publication bias monitoring and sensitivity analysis.Results:A total of 15 studies with 1337 patients were included in this meta-analysis.The results showed that at the 28-day mortality of patients with sepsis in the levosimendan group was not statistically superior to the 28-day mortality in the control group[RR=0.91,95%CI(0.78~1.06),Z=1.24,P=0.22].However,levosimendan can increase left ventricular ejection fraction,decrease left ventricular function index,increase cardiac index and decrease lactic acid in patients with sepsis.Conclusion:There is insufficient evidence to support a reduction in 28-day mortality in sepsis patients with levosimendan.However,levosimendan showed positive results on hemodynamic parameters,and more clinical trials are needed to verify the application of levosimendan in hemodynamic parameters of sepsis.展开更多
[Objectives] To investigate the clinical efficacy of intermittent levosimendan in the treatment of acute heart failure. [Methods] 100 patients diagnosed with acute heart failure and hospitalized in the internal medici...[Objectives] To investigate the clinical efficacy of intermittent levosimendan in the treatment of acute heart failure. [Methods] 100 patients diagnosed with acute heart failure and hospitalized in the internal medicine-cardiovascular department in The First People s Hospital of Yulin from January 2019 to February 2020 were randomly divided into two groups, 50 cases in each group. Both groups were treated with conventional anti-heart failure drugs. The control group was given levosimendan once, and the observation group was given levosimendan three times, with an interval of one month. The creatinine (Cr) level, serum NT proBNP, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were observed at 48 h before and after treatment and one month and two months after treatment in both groups. [Results] Compared with before treatment, the levels of NT-proBNP decreased in the two groups at 48 h after treatment, and the difference was statistically significant ( P <0.05). The Cr level of the control group did not change significantly before and after treatment, and the Cr level of the observation group decreased at one and two months after treatment compared with before treatment, with statistically significant differences ( P <0.05). Compared with before treatment, NT-proBNP and LVEDD decreased and LVEF increased at one and two months after treatment, and the differences were statistically significant ( P <0.05). There were no obvious adverse reactions in the two groups of patients during the treatment. [Conclusions] Repetitive use of levosimendan in the treatment of acute heart failure could significantly improve the renal function, cardiac contractility and cardiac function of patients, and with the passage of time, the treatment effect was improved, which is worthy of clinical promotion.展开更多
Background Acute myocardial depression caused by sepsis is an important cause of early death in sepsis patients.This study aimed to evaluate the effects of levosimendan on septic myocardial depression compared with th...Background Acute myocardial depression caused by sepsis is an important cause of early death in sepsis patients.This study aimed to evaluate the effects of levosimendan on septic myocardial depression compared with the control treatment.Methods A single-center study was conducted from Jan 15th 2019 to Jan 20th 2020.A total of 112 patients with septic myocardial depression were included and divided into levosimendan(LEV)group(n=49)and the control group(n=63)based on the administration of levosimendan.Clinical data including heart function,mechanical ventilation time,the length of intensive care unit(ICU)stay,the incidence of acute pulmonary edema and 28-day of survival rates were recorded.Results Compared with the control group,the improvement of left ventricular ejection fraction(LVEF)was greater in LEV group after one week treatment(52.41±4.62 vs.47.32±4.31,P=0.003).The level of N-terminal pro-brain natriuretic peptide(NT-pro-BNP)decreased more significantly(1882.92±190.61 pg/mL vs.3374.62±453.13 pg/mL,P=0.004).The mechanical ventilation time(112.43±9.11 h vs.135.34±12.54 h,P=0.013)and the length of ICU stay were also shorter(10.53±3.32 d vs.16.82±5.24 d,P=0.027)than that in the control group,and the incidence of acute pulmonary edema was lower(9.91%vs.17.22%,P=0.041).However,Kaplan-Meier analysis indicated there was no significant difference in both group for 28-day survival rates.Conclusions Levosimendan can improve cardiac function and shorten the duration of mechanical ventilation and ICU hospitalization for septic shock patients with myocardial depression.展开更多
Objective: To discuss the effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure. Methods: A total of 100 elderly patients with chronic heart fa...Objective: To discuss the effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure. Methods: A total of 100 elderly patients with chronic heart failure who were treated in the hospital between March 2014 and March 2017 were divided into control group and levosimendan group by random number table, each with 50 cases. Control group received clinical routine therapy for chronic heart failure, and levosimendan group received routine therapy combined with adjuvant levosimendan therapy. The differences in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes were compared between the two groups before and after treatment. Results: At T0, there was no statistically significant difference in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes between the two groups. At T1, serum RAAS indexes PRA, AngⅡ and ALD levels of levosimendan group were lower than those of control group;serum thyroid hormones TT3, TT4, FT3 and FT4 levels of levosimendan group were higher than those of control group;serum myocardial damage indexes cTnⅠ, H-FABP and NT-proBNP levels of levosimendan group were lower than those of control group;serum endothelial function index NO level of levosimendan group was higher than that of control group while ET-1 level was lower than that of control group. Conclusion: Adjuvant levosimendan therapy for elderly patients with chronic heart failure can effectively adjust the secretion of neuroendocrine hormones and reduce the myocardial and vascular endothelial damage.展开更多
Objective Levosimendan,a new calcium ion sensitizer,is currently used in the treatment of heart failure and as an option for patients with injury to the left heart or at high risk for surgery. The study tried to evalu...Objective Levosimendan,a new calcium ion sensitizer,is currently used in the treatment of heart failure and as an option for patients with injury to the left heart or at high risk for surgery. The study tried to evaluate the effects of levosimendan and ulinastain for protecting myocardium from ischemia-reperfusion (I / R) injury to展开更多
Background:Previous studies on whether or not levosimendan improved the prognosis of patients with sepsis and septic shock been inconsistent.We aimed to provide an updated analysis of the therapeutic value of levosime...Background:Previous studies on whether or not levosimendan improved the prognosis of patients with sepsis and septic shock been inconsistent.We aimed to provide an updated analysis of the therapeutic value of levosimendan in adult patients with sepsis and septic shock,in order to provide evidence-based medical evidence for its use.Methods:PubMed,Embase,Cochrane Library,Wanfang Data,and CNKI were searched until August 2018 without language restriction.Randomized controlled studies of levosimendan with either inotropic drugs or placebo for the treatment of sepsis or septic shock were enrolled.The primary outcome was mortality,and cardiac index and serum lactate levels were the secondary outcomes.Results:A total of 20 randomized controlled studies were included in this meta-analysis,including 1467 patients,with 738 patients in the experimental group(levosimendan group)and 729 patients in the control group(other inotropic drugs or placebo).There were no significant differences in mortality between the levosimendan and control groups(fixed-effect relative risk[RR]=0.90,95%confidence interval[CI][0.79,1.03],P=0.13).Levosimendan increased the cardiac index(VMD[weighted mean difference]=0.51,95%CI[0.06,0.95],P=0.02);and serum lactate levels were lower(VMD=—1.04,95%CI[—1.47,—0.60],P<0.00001).Conclusions:Based on current clinical evidence,levosimendan does not reduce mortality in adult critically ill patients with sepsis and septic shock.Physicians should use levosimendan with caution in patients with sepsis and septic shock.展开更多
Background:The role of prophylactic levosimendan in coronary surgery has not been established conclusively.Methods:Postoperative outcomes of 139 patients(mean age,68.2±9.6 years)having preoperative left ventricul...Background:The role of prophylactic levosimendan in coronary surgery has not been established conclusively.Methods:Postoperative outcomes of 139 patients(mean age,68.2±9.6 years)having preoperative left ventricular ejection fraction(LVEF)≤40%and undergoing isolated coronary surgery(2013-2017)were reviewed retrospectively.In 42(30.2%)patients(L-group),an intravenous infusion of levosimendan was started 24 hours before operation.The remaining 97(69.8%)patients were the control group(C-group).A comparison between the two groups regarding outcome of surgery was performed also after propensity matching.Results:Although the risk profile in L-patients was higher than in C-patients(median European System for Cardiac Operative Risk Evaluation II,10.5%vs.6.5%,P=0.013)due to higher prevalence of New York Heart Association class III-IV,LVEF≤30%,and preoperative intra-aortic balloon pump,in-hospital mortality was equivalent(4.8%vs.3.1%,P=0.48).However,low cardiac output,multiple blood transfusion,and any major complication early after surgery were more frequent in L-patients.After one-to-one propensity matching,which resulted in 15 pairs with similar baseline characteristics the use of levosimendan was associated with a trend towards an increased blood use(P=0.077),a higher frequency of any major complication(P=0.053),and lower peak serum levels of cardiac troponin I(P=0.088).No intergroup differences concerning mid-term survival or outcomes were found even for matched patients.Conclusions:When compared with traditional inotropes alone,prophylactic use of levosimendan showed clear benefits/drawbacks neither concerning immediate nor mid-term outcomes after coronary surgery.There could be any advantage in terms of myocardial preservation.展开更多
基金supported by the Hunan Provincial Science and Technology Major Special Fund(2021SK1020)the Natural Science Foundation of Hunan Province(2023JJ30948)+1 种基金the Health Commission of Hunan Province(202203014687)the International Medical Exchange Cardiovascular Multidisciplinary Integrated Thinking Research Foundation(Z-2016-23-2101-20),China.
文摘Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent impairment of the intestinal barrier.Levosimendan,a novel inotropic agent,binds to cardiac troponin C to enhance calcium sensitivity,activates ATP-dependent potassium channels in cardiomyocytes and vascular smooth muscle cells,exerts positive inotropic and vasodilatory effects,and reduces free radical generation,thereby improving systemic hemodynamics including intestinal circulation.However,clinical evidence regarding its protective effects on the intestinal barrier in HF patients remains limited,and the underlying mechanisms require further clarification.This study aims to investigate whether levosimendan confers protective effects on the intestinal barrier in HF patients and to explore its potential mechanisms.Methods:Network pharmacology was first used to analyze potential mechanisms of levosimendan in treating intestinal barrier dysfunction among HF patients.A total of 62 hospitalized patients with acute exacerbation of HF with reduced ejection fraction(HFrEF)were enrolled based on echocardiographic left ventricular ejection fraction.According to clinical medication regimens,patients were assigned to a conventional treatment group(n=31)or a levosimendan treatment group(n=31).The conventional treatment group received standard anti-HF therapy,while the levosimendan treatment group received levosimendan in addition to standard therapy.Enzyme-linked immunosorbent assays were used to measure plasma levels and changes in the intestinal-barrier proteins zonulin,intestinal fatty acid binding protein(I-FABP),proinflammatory cytokines[interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α],anti-inflammatory cytokine IL-10,and N-terminal probrain natriuretic peptide(NT-proBNP).Improvements in cardiac function and gastrointestinal symptoms were evaluated using the Kansas City Cardiomyopathy Questionnaire(KCCQ)and the Gastrointestinal Symptom Rating Scale(GSRS).Results:Network pharmacology indicated that the effects of levosimendan on intestinal barrier dysfunction in HF patients may involve inflammation-related pathways such as IL-17 and TNF.Clinically,after treatment,zonulin decreased by 32.94 ng/mL in the levosimendan treatment group versus 15.05 ng/mL in the conventional treatment group(P<0.05).I-FABP decreased by 6.97 pg/mL in the levosimendan treatment group but increased by 35.16 pg/mL in the conventional treatment group(P<0.05).IL-6,IL-17,and TNF-αdecreased by 1.11 pg/mL,1.21 pg/mL,and 2.83 pg/mL,respectively,in the levosimendan treatment group,whereas they increased by 7.68 pg/mL,0.67 pg/mL,and 2.38 pg/mL in the conventional treatment group(all P<0.05).IL-10 decreased by 24.48 pg/mL in the conventional treatment group but increased by 24.98 pg/mL in the levosimendan treatment group(P<0.05).NT-proBNP increased by 7.35 pg/mL in the conventional treatment group but decreased by 4.73 pg/mL in the levosimendan treatment group(P<0.05).KCCQ scores increased by 0.36 in the conventional treatment group and 1.86 in the levosimendan treatment group,GSRS scores decreased by 1.00 in the conventional treatment group and 2.40 in the levosimendan treatment group,respectively,but the differences were not statistically significant(both P>0.05).Conclusion:Levosimendan not only improves HF and gastrointestinal symptoms in hospitalized patients with acute exacerbation of HFrEF but also reduces plasma intestinal barrier factor levels.These effects may be associated with decreased plasma proinflammatory cytokines and increased anti-inflammatory cytokines after treatment,potentially involving IL-17 and TNF signaling pathways.
文摘Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1 was administered at a single dose of 6 μg·kg^-1 levosimendan by intravenous bolus injection within 10 min, and then followed by intravenous infusion for 4 h at a dose per minute of 0.05 μg·kg^-1·min^-1. Similarly, each subject in the group 2 （or group 3） was given by intravenous bolus injection at a dose of 12 μg·kg^-1 （or 18 μg·kg^-1） followed by an infusion at a dose of 0.10 μg·kg^-1·min^-1 （or 0.15 μg·kg^-1·min^-1） levosimendan. Blood samples were collected at 0 （prior to dosing）, 0.17, 0.5, 1, 2, 3, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8 and 10 h after administrations. Levosimendan concentrations in plasma were measured by LC-MS/MS method. The pharmacokinetic parameters were calculated using a software Drug and Statistic （version 2.0）. Results After administrations of levosimendan at various dose levels, the half-life （t1/2） values were 1.50 ± 0.35, 1.64 ± 0.25 and 1.54 ± 0.39 h; the maximal concentrations after injections （Co） were 9.54 ± 3.90, 15.95 ± 7.84 and 28.46 ± 10.74 ng·mL^-1; the areas under concentration-time （AUCo-t （t=7.8）） were 33.63± 9.34,54.39 ± 15.34 and 78.36 ± 23.74 ng ·mL^-1·h, respectively. Conclusion The C0 and A UC0-tvalues of levosimendan exhibited a dose-dependent manner, respectively. No differences in the pharmacokinetic parameters were observed between male and female Chinese subjects.
文摘Objective: To evaluate the clinical efficacy of levosimendan versus dobutamine in critically ill patients requiring inotropic support. Methods: Clinical trials were searched in PubMed, EMBASE, and the Cochrane Central Registry of Clinical Trials, as well as Web of Science. Studies were included if they compared levosimendan with dobutamine in critically ill patients requiring inotropic support, and provided at least one outcome of interest. Outcomes of interest included mortality, incidence of hypotension, supraventricular arrhythmias, and ventricular arrhythmias. Results: Data from a total of 3052 patients from 22 randomized controlled trials (RCTs) were included in the analysis. Overall analysis showed that the use of levosimendan was associated with a significant reduction in mortality (269 of 1373 [19.6%] in the levosimendan group, versus 328 of 1278 [25.7%] in the dobutamine group, risk ratio (RR)=0.81, 95% confidence interval (CI) 0.70-0.92, P for effect=0.002). Subgroup analysis indicated that the benefit from levosimendan could be found in the subpopulations of cardiac surgery, ischemic heart failure, and concomitant β-blocker therapy in comparison with dobutamine. There was no significant difference in the incidence of hypotension, supraventricular arrhythmias, or ventricular arrhythmias between the two drugs. Conclusions: In contrast with dobutamine, levosimendan is associated with a significant improvement in mortality in critically ill patients requiring inotropic support. Patients having cardiac surgery, with ischemic heart failure, and receiving concomitant β-blocker therapy may benefit from levosimendan. More RCTs are required to address the questions about no positive outcomes in the subpopulation in a cardiology setting, and to confirm the advantages in long-term prognosis.
文摘OBJECTIVE:To investigate the clinical effects of Xinkeshu combined with levosimendan on perioperative heart failure in oldest-old patients with hip fractures.METHODS:Oldest-old patients over 80 years old with perioperative heart failure and hip fractures were randomly divided into the control and observation groups,with 50 patients in each group.All patients in both groups were treated with conventional anti-heart failure therapy and levosimendan,whereas patients in the observation group additionally received Xinkeshu tablets.Clinical manifestations;left ventricular ejection fraction(LVEF);left ventricular end-diastolic dimension(LVEDD);left ventricular end-systolic dimension(LVESD);B-type natriuretic peptide(BNP),superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO),and endothelin-1(ET-1)levels;and self-rating anxiety scale(SAS)and self-rating depression scale(SDS)scores were compared between before and after treatment to evaluate the curative effects of Xinkeshu combined with levosimendan.RESULTS:After treatment,the efficacy rate was significantly higher in the observation group than in the control group.LVEF and the levels of SOD and NO were higher in the observation group than in the control group after treatment.However,LVEDD;LVESD;BNP,MDA,and ET-1 levels;and the SAS and SDS scores were lower after treatment in the observation group than in the control group.CONCLUSION:Levosimendan combined with Xinkeshu can improve cardiac function,alleviate oxidative stress,and relieve anxiety and depression in oldest-old patients with perioperative heart failure and hip fracture.
文摘Background: Left ventricular ejection fraction is an independent determinant of the outcome of coronary artery bypass surgery. Low preoperative ejection fraction requires special care in terms of pharmacological and mechanical inotropic support. Adrenaline is the most widely used inotropic drug, while levosimendan is a relatively new inotropic drug in the field of cardiac surgery. In this study, we aimed to evaluate the relative efficacy of levosimendan in low ejection fraction patients undergoing coronary artery bypass grafting (CABG). Methods: A retrospective comparative study was performed with 63 patients who underwent isolated on-pump elective CABG with a preoperative ejection fraction below 40%. Patients were allocated to the adrenaline group (n = 35) and levosimendan group (n = 28). Patients were further stratified according to ejection fraction above 30% and below or equal to 30%. The primary outcome was cardiac-related mortality, while other parameters were considered secondary endpoints. Results: EuroSCORE of the adrenaline group was 3.34 ± 1.26 and for the levosimendan group 3.15 ± 1.42 (p value 0.576). Nine patients of the adrenaline group had new postoperative atrial fibrillation compared to seven patients in the levosimendan group (p value 0.948). Two patients of the adrenaline group had postoperative ventricular arrhythmia compared to only one patient in the other group (p value 0.691). The adrenaline group had higher doses of inotropic support compared to the levosimendan group 210.84 ± 23.74 and 157.4 ± 22.69 ng/kg/min respectively (p value Conclusions: The levosimendan-based protocol failed to improve overall mortality in low ejection fraction patients undergoing CABG. However, this protocol significantly reduced the dose of inotropic and vasoconstrictor support needed, ventilation hours and duration of ICU stay.
文摘Aim: Increased oxidative stress plays important roles in vascular dysfunction in patients undergoing coronary artery bypass graft surgery. Hydrogen peroxide (H2O2) is used as an experimental model for oxidative stress. The present study was designed to assess the effects of levosimendan pretreatment on the contractile effects induced by H2O2 in human saphenous vein (HSV) segments. Methods: We studied H2O2 induced contractions of isolated HSV mounted in standard tissue baths. H2O2 (10-6 – 10-3 M) was added cumulatively to the organ bath. Concentration-response curves to H2O2 were repeated in the presence of levosimendan (10–8 M). In the second series of experiments, strips were contracted with 5-HT (10–5 M). When the contraction reached a stable plateau, H2O2 was administrated cumulatively into the organ bath. The same procedure was conducted in the presence of levosimendan. Results: Pretreatment of the SV strips with levosimendan significantly reduced the contractile response to each concentration of H2O2 . 5-HT produced contractions in SV strips. Further treatment of these strips with H2O2 resulted in statistically significant concentration-dependent increases in tension. Preincubation of the tissues with levosimendan did not significantly influence the maximum amplitude of the 5-HT-induced tone but inhibited the contractile effect of H2O2 on the 5-HT-induced contraction. Conclusion: Pretreatment of HSV with clinical concentrations of levosimendan inhibits the vasoconstriction caused by oxidative stress, indicating its potential preventive effect against oxidative stress induced graft spasm.
文摘Introduction: In this study we explicated early results of patients (the patients in whom levosimendan was used) who underwent coronary artery bypass graft surgery with ejection fraction 35% or less. We compared this group with the patients in whom levo-simendan was not used. Material and Methods: 97 patients who have 35% ejection fraction or less taken to isolated coronary artery bypass surgery between January 2009 and December 2011 in our clinic are chosen for this study retrospectively. We compared the patients in whom levosimendan was used with the patients in whom levosimendan was not used. Levo- simendan (Simdax, Abbott) has been used according to surgeon’s decision in patients. Results: The mean age of group 1 was 62.3 ± 7.6, and the mean age of group 2 was 59.3 ± 10.5 (p > 0.05). It was detected that the average ejection fraction was less in group 1 (p 0.05). It was found that need for blood transfusion were less in group 1 than group 2 (p 0.05). Conclusion: We consider levosimendan reduces need for blood transfusion in coronary artery bypass graft surgery. This results may change with increasing number of patients so we consider that multicenter larger study is needed.
基金This study was supported by National Natural Foundation Project of China(No81760341)。
文摘Objective:To investigate the effect of levosimendan on 28-day mortality in patients with sepsis.Methods:The English databases including Embase,PubMed,Web of Science,Cochrane Library and Chinese databasesincluding China National Knowledge Infrastructure(NKI),Wan fang Data,VIP,CBM were searched with levosimendan,sepsis and septic shock is as search terms.The published clinical randomized controlled trials of levosimendan injection were searched and the primary outcome measures of 28-day and 30-day mortality were included.Secondary outcome measures were left ventricular ejection fraction,left ventricular work index,cardiac index,and lactic acid.The literature retrieved is from the establishment of the database to October 2022.Stata 14.0 software was used for all data consolidation,publication bias monitoring and sensitivity analysis.Results:A total of 15 studies with 1337 patients were included in this meta-analysis.The results showed that at the 28-day mortality of patients with sepsis in the levosimendan group was not statistically superior to the 28-day mortality in the control group[RR=0.91,95%CI(0.78~1.06),Z=1.24,P=0.22].However,levosimendan can increase left ventricular ejection fraction,decrease left ventricular function index,increase cardiac index and decrease lactic acid in patients with sepsis.Conclusion:There is insufficient evidence to support a reduction in 28-day mortality in sepsis patients with levosimendan.However,levosimendan showed positive results on hemodynamic parameters,and more clinical trials are needed to verify the application of levosimendan in hemodynamic parameters of sepsis.
基金Supported by Scientific Research and Technology Development Program of Yulin City(20204031).
文摘[Objectives] To investigate the clinical efficacy of intermittent levosimendan in the treatment of acute heart failure. [Methods] 100 patients diagnosed with acute heart failure and hospitalized in the internal medicine-cardiovascular department in The First People s Hospital of Yulin from January 2019 to February 2020 were randomly divided into two groups, 50 cases in each group. Both groups were treated with conventional anti-heart failure drugs. The control group was given levosimendan once, and the observation group was given levosimendan three times, with an interval of one month. The creatinine (Cr) level, serum NT proBNP, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were observed at 48 h before and after treatment and one month and two months after treatment in both groups. [Results] Compared with before treatment, the levels of NT-proBNP decreased in the two groups at 48 h after treatment, and the difference was statistically significant ( P <0.05). The Cr level of the control group did not change significantly before and after treatment, and the Cr level of the observation group decreased at one and two months after treatment compared with before treatment, with statistically significant differences ( P <0.05). Compared with before treatment, NT-proBNP and LVEDD decreased and LVEF increased at one and two months after treatment, and the differences were statistically significant ( P <0.05). There were no obvious adverse reactions in the two groups of patients during the treatment. [Conclusions] Repetitive use of levosimendan in the treatment of acute heart failure could significantly improve the renal function, cardiac contractility and cardiac function of patients, and with the passage of time, the treatment effect was improved, which is worthy of clinical promotion.
基金National Natural Science Foundation of China(No.81701875)Science and Technology Program of Guangzhou,China(No.201904010039)Natural Science Foundation of Guangdong Province of China(No.10451008002006285)。
文摘Background Acute myocardial depression caused by sepsis is an important cause of early death in sepsis patients.This study aimed to evaluate the effects of levosimendan on septic myocardial depression compared with the control treatment.Methods A single-center study was conducted from Jan 15th 2019 to Jan 20th 2020.A total of 112 patients with septic myocardial depression were included and divided into levosimendan(LEV)group(n=49)and the control group(n=63)based on the administration of levosimendan.Clinical data including heart function,mechanical ventilation time,the length of intensive care unit(ICU)stay,the incidence of acute pulmonary edema and 28-day of survival rates were recorded.Results Compared with the control group,the improvement of left ventricular ejection fraction(LVEF)was greater in LEV group after one week treatment(52.41±4.62 vs.47.32±4.31,P=0.003).The level of N-terminal pro-brain natriuretic peptide(NT-pro-BNP)decreased more significantly(1882.92±190.61 pg/mL vs.3374.62±453.13 pg/mL,P=0.004).The mechanical ventilation time(112.43±9.11 h vs.135.34±12.54 h,P=0.013)and the length of ICU stay were also shorter(10.53±3.32 d vs.16.82±5.24 d,P=0.027)than that in the control group,and the incidence of acute pulmonary edema was lower(9.91%vs.17.22%,P=0.041).However,Kaplan-Meier analysis indicated there was no significant difference in both group for 28-day survival rates.Conclusions Levosimendan can improve cardiac function and shorten the duration of mechanical ventilation and ICU hospitalization for septic shock patients with myocardial depression.
文摘Objective: To discuss the effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure. Methods: A total of 100 elderly patients with chronic heart failure who were treated in the hospital between March 2014 and March 2017 were divided into control group and levosimendan group by random number table, each with 50 cases. Control group received clinical routine therapy for chronic heart failure, and levosimendan group received routine therapy combined with adjuvant levosimendan therapy. The differences in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes were compared between the two groups before and after treatment. Results: At T0, there was no statistically significant difference in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes between the two groups. At T1, serum RAAS indexes PRA, AngⅡ and ALD levels of levosimendan group were lower than those of control group;serum thyroid hormones TT3, TT4, FT3 and FT4 levels of levosimendan group were higher than those of control group;serum myocardial damage indexes cTnⅠ, H-FABP and NT-proBNP levels of levosimendan group were lower than those of control group;serum endothelial function index NO level of levosimendan group was higher than that of control group while ET-1 level was lower than that of control group. Conclusion: Adjuvant levosimendan therapy for elderly patients with chronic heart failure can effectively adjust the secretion of neuroendocrine hormones and reduce the myocardial and vascular endothelial damage.
文摘Objective Levosimendan,a new calcium ion sensitizer,is currently used in the treatment of heart failure and as an option for patients with injury to the left heart or at high risk for surgery. The study tried to evaluate the effects of levosimendan and ulinastain for protecting myocardium from ischemia-reperfusion (I / R) injury to
文摘Background:Previous studies on whether or not levosimendan improved the prognosis of patients with sepsis and septic shock been inconsistent.We aimed to provide an updated analysis of the therapeutic value of levosimendan in adult patients with sepsis and septic shock,in order to provide evidence-based medical evidence for its use.Methods:PubMed,Embase,Cochrane Library,Wanfang Data,and CNKI were searched until August 2018 without language restriction.Randomized controlled studies of levosimendan with either inotropic drugs or placebo for the treatment of sepsis or septic shock were enrolled.The primary outcome was mortality,and cardiac index and serum lactate levels were the secondary outcomes.Results:A total of 20 randomized controlled studies were included in this meta-analysis,including 1467 patients,with 738 patients in the experimental group(levosimendan group)and 729 patients in the control group(other inotropic drugs or placebo).There were no significant differences in mortality between the levosimendan and control groups(fixed-effect relative risk[RR]=0.90,95%confidence interval[CI][0.79,1.03],P=0.13).Levosimendan increased the cardiac index(VMD[weighted mean difference]=0.51,95%CI[0.06,0.95],P=0.02);and serum lactate levels were lower(VMD=—1.04,95%CI[—1.47,—0.60],P<0.00001).Conclusions:Based on current clinical evidence,levosimendan does not reduce mortality in adult critically ill patients with sepsis and septic shock.Physicians should use levosimendan with caution in patients with sepsis and septic shock.
文摘Background:The role of prophylactic levosimendan in coronary surgery has not been established conclusively.Methods:Postoperative outcomes of 139 patients(mean age,68.2±9.6 years)having preoperative left ventricular ejection fraction(LVEF)≤40%and undergoing isolated coronary surgery(2013-2017)were reviewed retrospectively.In 42(30.2%)patients(L-group),an intravenous infusion of levosimendan was started 24 hours before operation.The remaining 97(69.8%)patients were the control group(C-group).A comparison between the two groups regarding outcome of surgery was performed also after propensity matching.Results:Although the risk profile in L-patients was higher than in C-patients(median European System for Cardiac Operative Risk Evaluation II,10.5%vs.6.5%,P=0.013)due to higher prevalence of New York Heart Association class III-IV,LVEF≤30%,and preoperative intra-aortic balloon pump,in-hospital mortality was equivalent(4.8%vs.3.1%,P=0.48).However,low cardiac output,multiple blood transfusion,and any major complication early after surgery were more frequent in L-patients.After one-to-one propensity matching,which resulted in 15 pairs with similar baseline characteristics the use of levosimendan was associated with a trend towards an increased blood use(P=0.077),a higher frequency of any major complication(P=0.053),and lower peak serum levels of cardiac troponin I(P=0.088).No intergroup differences concerning mid-term survival or outcomes were found even for matched patients.Conclusions:When compared with traditional inotropes alone,prophylactic use of levosimendan showed clear benefits/drawbacks neither concerning immediate nor mid-term outcomes after coronary surgery.There could be any advantage in terms of myocardial preservation.
