BACKGROUND At present,large-scale studies on the clinical characteristics of sepsis-induced cardiomyopathy(SIC)are lacking.AIM To investigate the clinical characteristics of SIC.METHODS Based on the analysis of the MI...BACKGROUND At present,large-scale studies on the clinical characteristics of sepsis-induced cardiomyopathy(SIC)are lacking.AIM To investigate the clinical characteristics of SIC.METHODS Based on the analysis of the MIMIC-III public database,we performed a largescale retrospective study involving sepsis patients who were admitted to the intensive care unit(ICU)and had no concomitant cardiac disease.We used propensity score matching analysis and multivariate logistic regression to ensure the robustness of the results.The primary outcome was hospital mortality,and the secondary outcomes included the number of patients who received mechanical ventilation or renal replacement therapy during their hospital stay,the number of patients administered with vasopressors,the length of ICU stay,and the length of hospital stay.RESULTS In the present study,after screening 38605 patients,3530 patients with sepsis were included.A total of 997 patients met the SIC diagnostic criteria,and the incidence of SIC was 28.20%(95%confidence interval[CI]:26.80%-29.70%).Compared to patients in the non-SIC group,patients in the SIC group were of older age and had a higher Simplified Acute Physiology Score(SAPS)-Ⅰ score,SAPS-Ⅱ score,and Elixhauser comorbidity index(ECI).A total of 367(36.8%)of 997 patients in the SIC group and 818(32.3%)of 2533 patients in the non-SIC group died in the hospital,which resulted in a significant between-group difference(odds ratios=1.22,95%CI:1.05-1.42;P=0.011).For the secondary outcomes,more patients in the SIC group received mechanical ventilation and vasopressors.Multivariate logistic regression analysis showed that age,male sex,ECI,hemoglobin level,diabetes,and mechanical ventilation use on the first day of ICU admission were risk factors for SIC.CONCLUSION Compared with non-SIC patients,hospital mortality is higher in SIC patients.展开更多
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.The heart is one of the most important oxygen delivery organs,and dysfunction significantly increases the mor...Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.The heart is one of the most important oxygen delivery organs,and dysfunction significantly increases the mortality of the body.Hence,the heart has been studied in sepsis for over half a century.However,the definition of sepsis-induced cardiomyopathy is not unified yet,and the conventional conception seems outdated:left ventricular systolic dysfunction(LVSD)along with enlargement of the left ventricle,recovering in 7 to 10 days.With the application of echocardiography in intensive care units,not only LVSD but also left ventricular diastolic dysfunction,right ventricular dysfunction,and even diffuse ventricular dysfunction have been seen.The recognition of sepsis-induced cardiomyopathy is gradually becoming complete,although our understanding of it is not deep,which has made the diagnosis and treatment stagnate.In this review,we summarize the research on sepsis-induced cardiomyopathy.Women and young people with septic cardiomyopathy are more likely to have LVSD,which may have the same mechanism as stress cardiomyopathy.Elderly people with ischemic cardiomyopathy and hypertension tend to have left ventricular diastolic dysfunction.Patients with mechanical ventilation,acute respiratory distress syndrome or other complications of increased right ventricular afterload mostly have right ventricular dysfunction.Diffuse cardiac dysfunction has also been shown in some studies;patients with mixed or co-existing cardiac dysfunction are more common,theoretically.Thus,understanding the pathophysiology of sepsis-induced cardiomyopathy from the perspective of critical care echocardiography is essential.展开更多
Background:Sepsis-induced cardiomyopathy(SIC)is an identified serious complication of sepsis that is associated with adverse outcomes and high mortality.Heat shock proteins(HSPs)have been implicated in suppressing sep...Background:Sepsis-induced cardiomyopathy(SIC)is an identified serious complication of sepsis that is associated with adverse outcomes and high mortality.Heat shock proteins(HSPs)have been implicated in suppressing septic inflammation.The aim of this study was to investigate whether HSP70 can attenuate cellular mitochondrial dysfunction,exuberated inflammation and inflammasome-mediated pyroptosis for SIC intervention.Methods:Mice with cecal ligation plus perforation(CLP)and lipopolysaccharide(LPS)-treated H9C2 cardiomyocytes were used as models of SIC.The mouse survival rate,gross profile,cardiac function,pathological changes and mitochondrial function were observed by photography,echocardiography,hematoxylin-eosin staining and transmission electron microscopy.In addition,cell proliferation and the levels of cardiac troponin I(cTnI),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were determined by Cell Counting Kit-8,crystal violet staining and enzyme-linked immunosorbent assay.Moreover,mitochondrial membrane potential was assessed by immunofluorescence staining,and dynamin-related protein 1 and pyroptosis-related molecules[nucleotide-binding domain,leucine-rich-repeat containing family pyrin domain-containing 3(NLRP3),caspase-1,gasdermin-D(GSDMD),gasdermin-D N-terminal(GSDMD-N)]were measured by western blotting,immunoprecipitation and immunoblotting.Finally,hsp70.1 knockout mice with CLP were used to verify the effects of HSP70 on SIC and the underlying mechanism.Results:Models of SIC were successfully established,as reduced consciousness and activity with liparotrichia in CLP mice were observed,and the survival rate and cardiac ejection fraction(EF)were decreased;conversely,the levels of cTnI,TNF-αand IL-1βand myocardial tissue damage were increased in CLP mice.In addition,LPS stimulation resulted in a reduction in cell viability,mitochondrial destabilization and activation of NLRP3-mediated pyroptosis molecules in vitro.HSP70 treatment improved myocardial tissue damage,survival rate and cardiac dysfunction caused by CLP.Additionally,HSP70 intervention reversed LPS-induced mitochondrial destabiliza-tion,inhibited activation of the NLRP3 inflammasome,caspase-1,GSDMD and GSDMD-N,and decreased pyroptosis.Finally,knockout of hsp70.1 mice with CLP aggravated cardiac dysfunction and upregulated NLRP3 inflammasome activity,and exogenous HSP70 significantly rescued these changes.It was further confirmed that HSP70 plays a protective role in SIC by attenuating mitochondrial dysfunction and inactivating pyroptotic molecules.Conclusions:Our study demonstrated that mitochondrial destabilization and NLRP3 inflammasome activation-mediated pyroptosis are attributed to SIC.Interestingly,HSP70 ameliorates sepsis-induced myocardial dysfunction by improving mitochondrial dysfunction and inhibiting the acti-vation of NLRP3 inflammasome-mediated pyroptosis,and such a result may provide approaches for novel therapies for SIC.展开更多
Sepsis is a common clinical disease;if there is no early active treatment,it is likely to develop into multiple organ dysfunction syndrome and even cause death.Septic cardiomyopathy is a complication of sepsis-related...Sepsis is a common clinical disease;if there is no early active treatment,it is likely to develop into multiple organ dysfunction syndrome and even cause death.Septic cardiomyopathy is a complication of sepsis-related cardiovascular failure,characterized by reversible left ventricular dilatation and decreased ventricular systolic and/or diastolic function.At present,echocardiography and biomarkers are often used to screen septic cardiomyopathy in clinics.Although there is still a lack of clear diagnostic criteria for septic cardiomyopathy,according to existing studies,the pathogenesis of several septic cardiomyopathy has been clarified,such as immune response caused by infection and mitochondrial dysfunction.This review summarizes the characteristics,pathophysiology,and diagnosis of septic cardiomyopathy and focuses on the mechanisms of infection immunity and mitochondrial dysfunction.展开更多
基金Supported by Science and Technology Program of Guangzhou Science,Technology,and Innovation Commission,No.201904010258.
文摘BACKGROUND At present,large-scale studies on the clinical characteristics of sepsis-induced cardiomyopathy(SIC)are lacking.AIM To investigate the clinical characteristics of SIC.METHODS Based on the analysis of the MIMIC-III public database,we performed a largescale retrospective study involving sepsis patients who were admitted to the intensive care unit(ICU)and had no concomitant cardiac disease.We used propensity score matching analysis and multivariate logistic regression to ensure the robustness of the results.The primary outcome was hospital mortality,and the secondary outcomes included the number of patients who received mechanical ventilation or renal replacement therapy during their hospital stay,the number of patients administered with vasopressors,the length of ICU stay,and the length of hospital stay.RESULTS In the present study,after screening 38605 patients,3530 patients with sepsis were included.A total of 997 patients met the SIC diagnostic criteria,and the incidence of SIC was 28.20%(95%confidence interval[CI]:26.80%-29.70%).Compared to patients in the non-SIC group,patients in the SIC group were of older age and had a higher Simplified Acute Physiology Score(SAPS)-Ⅰ score,SAPS-Ⅱ score,and Elixhauser comorbidity index(ECI).A total of 367(36.8%)of 997 patients in the SIC group and 818(32.3%)of 2533 patients in the non-SIC group died in the hospital,which resulted in a significant between-group difference(odds ratios=1.22,95%CI:1.05-1.42;P=0.011).For the secondary outcomes,more patients in the SIC group received mechanical ventilation and vasopressors.Multivariate logistic regression analysis showed that age,male sex,ECI,hemoglobin level,diabetes,and mechanical ventilation use on the first day of ICU admission were risk factors for SIC.CONCLUSION Compared with non-SIC patients,hospital mortality is higher in SIC patients.
文摘Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.The heart is one of the most important oxygen delivery organs,and dysfunction significantly increases the mortality of the body.Hence,the heart has been studied in sepsis for over half a century.However,the definition of sepsis-induced cardiomyopathy is not unified yet,and the conventional conception seems outdated:left ventricular systolic dysfunction(LVSD)along with enlargement of the left ventricle,recovering in 7 to 10 days.With the application of echocardiography in intensive care units,not only LVSD but also left ventricular diastolic dysfunction,right ventricular dysfunction,and even diffuse ventricular dysfunction have been seen.The recognition of sepsis-induced cardiomyopathy is gradually becoming complete,although our understanding of it is not deep,which has made the diagnosis and treatment stagnate.In this review,we summarize the research on sepsis-induced cardiomyopathy.Women and young people with septic cardiomyopathy are more likely to have LVSD,which may have the same mechanism as stress cardiomyopathy.Elderly people with ischemic cardiomyopathy and hypertension tend to have left ventricular diastolic dysfunction.Patients with mechanical ventilation,acute respiratory distress syndrome or other complications of increased right ventricular afterload mostly have right ventricular dysfunction.Diffuse cardiac dysfunction has also been shown in some studies;patients with mixed or co-existing cardiac dysfunction are more common,theoretically.Thus,understanding the pathophysiology of sepsis-induced cardiomyopathy from the perspective of critical care echocardiography is essential.
文摘Background:Sepsis-induced cardiomyopathy(SIC)is an identified serious complication of sepsis that is associated with adverse outcomes and high mortality.Heat shock proteins(HSPs)have been implicated in suppressing septic inflammation.The aim of this study was to investigate whether HSP70 can attenuate cellular mitochondrial dysfunction,exuberated inflammation and inflammasome-mediated pyroptosis for SIC intervention.Methods:Mice with cecal ligation plus perforation(CLP)and lipopolysaccharide(LPS)-treated H9C2 cardiomyocytes were used as models of SIC.The mouse survival rate,gross profile,cardiac function,pathological changes and mitochondrial function were observed by photography,echocardiography,hematoxylin-eosin staining and transmission electron microscopy.In addition,cell proliferation and the levels of cardiac troponin I(cTnI),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were determined by Cell Counting Kit-8,crystal violet staining and enzyme-linked immunosorbent assay.Moreover,mitochondrial membrane potential was assessed by immunofluorescence staining,and dynamin-related protein 1 and pyroptosis-related molecules[nucleotide-binding domain,leucine-rich-repeat containing family pyrin domain-containing 3(NLRP3),caspase-1,gasdermin-D(GSDMD),gasdermin-D N-terminal(GSDMD-N)]were measured by western blotting,immunoprecipitation and immunoblotting.Finally,hsp70.1 knockout mice with CLP were used to verify the effects of HSP70 on SIC and the underlying mechanism.Results:Models of SIC were successfully established,as reduced consciousness and activity with liparotrichia in CLP mice were observed,and the survival rate and cardiac ejection fraction(EF)were decreased;conversely,the levels of cTnI,TNF-αand IL-1βand myocardial tissue damage were increased in CLP mice.In addition,LPS stimulation resulted in a reduction in cell viability,mitochondrial destabilization and activation of NLRP3-mediated pyroptosis molecules in vitro.HSP70 treatment improved myocardial tissue damage,survival rate and cardiac dysfunction caused by CLP.Additionally,HSP70 intervention reversed LPS-induced mitochondrial destabiliza-tion,inhibited activation of the NLRP3 inflammasome,caspase-1,GSDMD and GSDMD-N,and decreased pyroptosis.Finally,knockout of hsp70.1 mice with CLP aggravated cardiac dysfunction and upregulated NLRP3 inflammasome activity,and exogenous HSP70 significantly rescued these changes.It was further confirmed that HSP70 plays a protective role in SIC by attenuating mitochondrial dysfunction and inactivating pyroptotic molecules.Conclusions:Our study demonstrated that mitochondrial destabilization and NLRP3 inflammasome activation-mediated pyroptosis are attributed to SIC.Interestingly,HSP70 ameliorates sepsis-induced myocardial dysfunction by improving mitochondrial dysfunction and inhibiting the acti-vation of NLRP3 inflammasome-mediated pyroptosis,and such a result may provide approaches for novel therapies for SIC.
基金supported by grants from the National Natural Science Foundation of China(82172165)Taishan Young Scholar Program of Shandong Province(tsqn202103171)+1 种基金Project was funded by China Postdoctoral Science Foundation(2020T130072ZX)Clinical Research Center of Shandong University(2020SDUCRCC007).
文摘Sepsis is a common clinical disease;if there is no early active treatment,it is likely to develop into multiple organ dysfunction syndrome and even cause death.Septic cardiomyopathy is a complication of sepsis-related cardiovascular failure,characterized by reversible left ventricular dilatation and decreased ventricular systolic and/or diastolic function.At present,echocardiography and biomarkers are often used to screen septic cardiomyopathy in clinics.Although there is still a lack of clear diagnostic criteria for septic cardiomyopathy,according to existing studies,the pathogenesis of several septic cardiomyopathy has been clarified,such as immune response caused by infection and mitochondrial dysfunction.This review summarizes the characteristics,pathophysiology,and diagnosis of septic cardiomyopathy and focuses on the mechanisms of infection immunity and mitochondrial dysfunction.
