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Objective:To evaluate the feasibility of using bedside ultrasound and serum biomarkers for the prediction of sepsis-induced myocardial dysfunction(SIMD)and mortality in septic shock patients.Methods:The patients diagnosed as septic shock were enrolled in the study from January 2019 to July 2021 in PICU at Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine.Bedside ultrasound results were recorded at day 1, 2, 3, 7 and 10.Blood samples were collected at the same time, markers of myocardial injury were detected, and prognosis was recorded at 28 days.According to the left ventricular ejection fraction (LVEF), children with septic shock were divided into SIMD group and non-SIMD group.Those with LVEF <50% or decreased by ≥10% from baseline level were defined as SIMD.Differences in cardiac ultrasound parameters and biomarkers between two groups were compared.Logistic regression analysis was performed to determine the independent risk factors for SIMD and the independent risk factors for death at 28 days after septic shock.The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of different indicators in predicting SIMD and the death outcome of children with septic shock on 28 days.Results:A total of 57 children were enrolled, including 28 cases in SIMD group and 29 cases in non-SIMD group.Univariate analysis showed that there were statistically significant differences in pediatric critical illness score, N-terminal B-type natriuretic peptide(NT-proBNP), LVEF and left ventricular short axis shortening rate between two groups ( P<0.05). Logistic analysis demonstrated that LVEF( OR=0.890, 95% CI 0.818-0.969, P=0.007)and NT-proBNP ( OR=1.000, 95% CI 1.000-1.000, P=0.015)could independently predict SIMD.There were 42 cases in survival group and 15 in non-survival group according to the prognosis on 28 days.Univariate analysis showed that there were significant differences in pediatric risk mortality score Ⅲ, pediatric sequential organ failure assessment, cardiac troponin I, and mitral annular plane systolic excursion(MAPSE)( P<0.05). Logistic analysis showed that only MAPSE independently predicted mortality( OR=85.670, 95% CI 1.685-4 356.736, P=0.026). Compared with MAPSE(AUC=0.727), MAPSE combined with pediatric risk mortality score Ⅲ, pediatric sequential organ failure assessment, cardiac troponin I(AUC=0.926) could be better to predict the 28 days prognosis of patients with septic shock on 28 days. Conclusion:NT-proBNP increases significantly in the early stage of SIMD.MAPSE shows no difference between SIMD and non-SIMD patients.MAPSE is correlated with the prognosis of patient with septic shock.
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Objective:To systematically review the relationship between the sepsis-induced myocardial dysfunction and hypertension.Methods:PubMed, Embase, Cochrane Library, China National Knowledge Internet (CNKI), China Biology Medicine (CBM) and Wanfang were searched both with Chinese and English keywords from the establishment of the database to January 2022 on the correlation between sepsis-induced myocardial dysfunction and hypertension. Newcastle-Ottawa Quality Assessment Scale (NOS) was used to evaluate the literature quality, and Stata 12.0 software was used to perform meta-analysis on the included literature.Results:After screening, 16 literatures were included, a total of 3 758 subjects was involved. Meta-analysis results showed that patients with hypertension had a higher incidence of sepsis-induced myocardial dysfunction, and the results were statistically significant. Subgroup analysis and sensitivity analysis suggested stable results.Conclusions:Hypertension is a risk factor for sepsis-induced myocardial dysfunction, and the results are statistically significant. Early intervention may improve the prognosis of septic patients.
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Objective:To investigate the role and mechanism of microRNA-499 (miR-499) regulating α-myosin heavy chain (α-MHC) and β-myosin heavy chain (β-MHC) gene axis in septic myocardial dysfunction (SMD) and its significance.Methods:Sixty healthy adult male Sprague-Dawley (SD) rats were divided into phosphate buffered saline (PBS) control group (PBS group), lipopolysaccharide (LPS) induced SMD model group (LPS group), miR-499 agonist pretreatment group (agomir+LPS group), and miR-499 inhibitor pretreatment group (antagomir+LPS group) by random number table, with 15 rats in each group. SMD rat model was reproduced by intraperitoneal injection of LPS 10 mg/kg. The PBS group was intraperitoneally injected with the same amount of PBS. The two pretreatment groups were injected with agomir 30 mg/kg or antagomir 80 mg/kg through the caudal vein for 3 days, once a day. PBS group and LPS group were not pretreated. Echocardiography was detected 5 hours after LPS injection, and relevant indexes were recorded. The expression of miR-499 in plasma and myocardial tissue was detected by real-time quantitative polymerase chain reaction (qPCR). Western blotting was used to detect the protein expressions of α-MHC and β-MHC in myocardial tissue. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of heart failure, was measured by electrochemiluminescence.Results:Compared with the PBS group, the rats in LPS group were depressed. Additionally, LPS down-regulated the level of miR-499 in plasma and myocardial tissue, decreased α-MHC expression in myocardial tissue and up-regulated the expression of β-MHC. Echocardiography showed that left ventricular ejection fraction (LVEF), left ventricle fractional shortening (LVFS), cardiac output (CO), stroke volume (SV) and heart rate (HR) decreased by 49.1%, 59.2%, 48.8%, 39.4% and 15.9%, respectively, and the level of plasma NT-proBNP increased significantly in LPS group, indicating that LPS could induce cardiac dysfunction in rats. Compared with the LPS group, after pretreatment with agomir to overexpress the miR-499, LVEF and LVFS were significantly increased [LVEF: 0.662±0.020 vs. 0.323±0.024, LVFS: (36.16±1.43)% vs. (20.20±1.32)%, both P < 0.01], which suggested that the cardiac function of rats was improved in agomir+LPS group. At the same time, pretreatment with agomir significantly down-regulated the β-MHC protein expression (β-MHC/GAPDH: 0.74±0.04 vs. 2.97±0.34, P < 0.01), significantly up-regulated α-MHC protein expression (α-MHC/GAPDH: 1.59±0.05 vs. 0.74±0.14, P < 0.01), and significantly decreased the plasma NT-proBNP level (ng/L: 114.49±6.85 vs. 334.13±4.36, P < 0.01). After pretreatment with antagomir to inhibit the expression of miR-499, echocardiography showed that LVEF and LVFS were significantly lower than those in the LPS group [LVEF: 0.297±0.021 vs. 0.323±0.024, LVFS: (19.38±1.52)% vs. (21.20±1.32)%, both P < 0.01], which suggested that the cardiac function of rats was significantly inhibited. At the same time, pretreatment with antagomir significantly down-regulated α-MHC protein expression in myocardial tissue (α-MHC/GAPDH: 0.63±0.03 vs. 0.74±0.14, P < 0.01), significantly up-regulated β-MHC protein expression (β-MHC/GAPDH: 3.03±0.47 vs. 2.97±0.34, P < 0.01), and significantly increased the level of plasma NT-proBNP (ng/L: 373.91±4.23 vs. 334.13±4.36, P < 0.05). Conclusions:miR-499 could regulate the expression of α-MHC and β-MHC which improved cardiac dysfunction caused by sepsis. Targeted regulation of miR-499 expression may be an effective way to treat SMD.
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Objective:To observe the changes of serum histone H4 level and its predictive value in patients with septic cardiomyopathy.Methods:A prospective study was conducted. A total of 147 patients with sepsis and septic shock were collected in emergency department. The general data were recorded. Transthoracic echocardiography and plasma histone H4 were conducted within 24 hours and 7 days after admission.The scores of sequential organ failure assessment(SOFA), acute physiology and chronic health evaluationⅡ(APACHEⅡ), and nutritional risk screening 2002 (NRS2002) were evaluated within 24 hours. According to whether septic cardiomyopathy occurred, the patients were divided into two groups, and dynamic changes of histone H4 on the first and seventh day of the two groups were observed. The factors influencing the occurrence of septic cardiomyopathy were analyzed by multivariate logistic regression. The prediction ability of serum histone H4 on septic cardiomyopathy was evaluated by receiver operating curve (ROC).Results:The incidence of septic cardiomyopathy was 28.6% (42 / 147). The level of histone H4 in septic cardiomyopathy group was higher than that in non septic cardiomyopathy group ( Z = 4.449, P < 0.001), and dynamic detection showed that the level of histone H4 on the seventh day was lower than that on admission ( Z=3.057, P=0.002). Multivariate logistic regression showed that the high serum histone H4 level [Odd Ratio( OR)=1.337, 95% confidence interval (95% CI) was 1.173-1.522, P < 0.001], SOFA ( OR= 1.474, 95% CI 1.227-1.769, P < 0.001), older age ( OR = 1.074, 95% CI 1.019-1.132, P = 0.008) were independent risk factors for septic cardiomyopathy. The area of ROC curve for serum histone H4 to predict septic cardiomyopathy was 0.729 ( P < 0.001), the predictive cut-off value was 10.81 ng/ml, which yielded a sensitivity 0.524 and a specificity of 0.914. Conclusions:The level of histone H4 showed dynamic change in septic cardiomyopathy, and high serum histone H4 level has a good predictive value for the occurrence of septic cardiomyopathy.
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OBJECTIVE@#To investigate whether Shenfu Injection (SFI, ) can alleviate post-resuscitation myocardial dysfunction by inhibiting the inflammatory response.@*METHODS@#After 8 min of ventricular fibrillation and 2 min of basic life support, 24 pigs were randomly divided into 3 groups (n=8), which were given intravenous bolus injections of SFI (1.0 mL/kg), epinephrine (EP, 0.02 mg/kg) and normal saline (SA), respectively. The animals were sacrificed at 24 h after restoration of spontaneous circulation (ROSC), and serum interleuking-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay (ELISA); expressions of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) mRNAs and proteins were determined by RT-PCR and Western blot, respectively.@*RESULTS@#Compared with the EP and the SA groups, the ultrastructure of myocardial cells were slightly damaged and the systolic function of the left ventricle was markedly improved in the SFI group at 24 h after ROSC (P<0.05). In addition, compared with the EP and SA groups, the SFI group also showed significantly reduced levels of serum IL-6 and TNF-α, protein and mRNA levels of myocardial NF- κB and TLR4 (P<0.05).@*CONCLUSIONS@#Activation of TLR4/NF-κB signaling pathway may be involved in the pathological mechanisms of post-resuscitation myocardial dysfunction. SFI may block NF-κB-mediated inflammatory response by reducing the activity of NF- κB and the level of TNF-α, thus playing a protective role in post-resuscitation myocardial dysfunction.
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OBJECTIVE@#To evaluate the protective effects of Astragaloside IV (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP).@*METHODS@#The model of sepsis-induced cardiac dysfunction was induced by CLP. Using a random number table, 50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups: the sham group (sham), the model group (CLP, 18 h/72 h) and AST group (18 h/72 h). Except the sham group, the rats in other groups received CLP surgery to induce sepsis. CLP groups received intragastric administration with normal saline after CLP. AST groups received intragastric administration with AST solution (40 mg/kg) once a day. The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay (ELISA) at different time point, such as interleukin 6 (IL-6), IL-10, high mobility group box-1 protein B1 (HMGB-1), superoxide dismutase (SOD), and malondialdehyde (MDA). Cardiac function was determined by echocardiography. Moreover, changes in myocardial pathology were evaluated using hematoxylin and eosin staining. The levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were analysed to determine the status of CLP-induced myocardium. In addition, the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), IκB kinase α (IKKα), nuclear factor kappa B p65 (NF-κB p65) were detected by Western blot analysis. Moreover, survival rate was investigated.@*RESULTS@#AST improved the survival rate of CLP-induced rats by up to 33.3% (P<0.05). The cardioprotective effect of AST was observed by increased ejection fraction, fractional shortening and left ventricular internal diameter in diastole respectively (P<0.01 or P<0.05). Subsequently, AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium, as well as the histological alterations of myocardium (P<0.01 or P<0.05); the generation of inflammatory cytokines (IL-6, IL-10, HMGB-1) and oxidative stress markers (SOD, MDA) in the serum was significantly alleviated (P<0.01 or P<0.05). On the other hand, AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (P<0.01 or P<0.05).@*CONCLUSIONS@#AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome. The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes.
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Animals , Rats , Disease Models, Animal , Heart Diseases , NF-kappa B , Rats, Sprague-Dawley , Saponins , Sepsis/drug therapy , Triterpenes , Tumor Necrosis Factor-alphaABSTRACT
Objective To investigate the effects of therapeutic hypothermia (TH) on myocardial Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) and cell autophagy after cardiopulmonary resuscitation (CPR) in swine.Methods Twenty healthy male domestic swine weighing 33-40 kg were randomly (random number) divided into 3 groups:sham group (n=4),CPR group (n=8) and TH group (n=8).Sham animals only underwent general preparation without experiencing cardiac arrest and resuscitation.The animal model was established by 8 min of electrically induced ventricular fibrillation and then 5 min CPR in the CPR and TH groups.Successful resuscitation was regarded as an organized rhythm with a mean arterial pressure of greater than 50 mmHg for 5 min or more.After successful resuscitation,body temperature was decreased to 33 ℃ by a cooling blanket and then maintained until 24 h post-resuscitation,and followed by a rewarming at a rate of 1 ℃/h for 5 h in the TH group.A normal temperature was maintained by the blanket throughout the experiment in the sham and CPR groups.At 6,12,24 and 30 h after resuscitation,the values of stroke volume (SV) and global ejection fraction (GEF) were measured by PiCCO,and meanwhile the serum concentrations of cardiac troponin Ⅰ (cTnI) were measured by ELISA assay and the serum activities of creatine kinase-MB (CK-MB) were evaluated by an automatic biochemical analyzer.At 30 h after resuscitation,the animals were sacrificed and left ventricular myocardium was obtained for the determination ofCaMK Ⅱ,microtubule-associated protein light chain 3 Ⅱ (LC3 Ⅱ) and p62 expressions by Western blot.The variables were compared with One way analysis of variance and then the Bonferroni test among the three groups.Results Compared with the sham group,myocardial dysfunction and injury after resuscitation were observed in the CPR and TH groups,which were indicated by decreased SV and GEF and also increased cTnI concentration and CK-MB activity in serum (all P＜0.05).Compared with the CPR group,the values of SV and GEF were significantly increased at 6 h after resuscitation,and serum cTnI concentration and CK-MB activity were significantly decreased starting 12 h after resuscitation in the TH group [SV (mL):25.0±6.9 vs 31.9±3.3 at 6 h,26.7±5.1 vs 34.6±3.7 at 12 h,28.8±3.3 vs 35.7±3.2 at 24 h,29.2±5.2 vs 36.7±3.3 at 30 h;GEF (％):17.1±2.7 vs 19.9±1.8 at 6 h,18.7±1.9 vs 21.6±1.8 at 12 h,19.3±2.3 vs 23.0±2.4 at 24 h,21.0±1.7 vs 23.7±1.7 at 30 h;cTnI (pg/mL):564±51 vs 466±56 at 12 h,534±38 vs 427±60 at 24 h,476±55 vs 375±46 at 30 h;CK-MB (U/L):803±164 vs 652±76 at 12 h,693±96 vs 557±54 at 24 h,633±91 vs 480±77 at 30 h,all P＜0.05].Tissue detection indicated that the expression of CaMK Ⅱ and LC3 Ⅱ were increased while the expression of p62 was decreased in post-resuscitation myocardium in the CPR and TH groups compared with the sham group (all P＜0.05).However,the expression of CaMK Ⅱ and LC3 Ⅱ were decreased and the expression of p62 was increased in postresuscitation myocardium in the TH group compared to the CPR group (CaMK Ⅱ:0.73±0.06 vs 0.58±0.05;LC3 Ⅱ:0.69±0.09 vs 0.50±0.07;p62:0.40±0.07 vs 0.68±0.14,all P＜0.05).Conclusion The mechanism of TH alleviating post-resuscitation myocardial dysfunction and injury may be related to the inhibition of CaMK Ⅱ expression and cell autophagy.
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BACKGROUND: It is currently believed that myocardial mitochondrial structure and function damage play a key role in sepsis-induced myocardial dysfunction. OBJECTIVE: To construct a rat model of sepsis-induced myocardial dysfunction and provide an effective experimental method for studying the disease. METHODS: Seventy-two SPF male Sprague-Dawley rats were randomly divided into control group (n-28) and lipopolysaccharide (LPS) group (n=44). Twenty rats were randomly selected from each group for observation of 10 days of survival. According to the post-modeling phase, the remaining 24 rats of the LPS group were divided into three subgroups, LPS 6-hour group, LPS 12-hour group and LPS 24-hour group, with 8 rats in each group. A sepsis model was constructed by intraperitoneal injection of 10 mg/kg LPS in the LPS group, and the control group was injected with an equal volume of normal saline. Echocardiographic examination of cardiac function was performed at each phase in each LPS subgroup. Myocardial histopathological morphology was observed by light microscopy, and myocardial ultrastructure was observed by transmission electron microscopy. Serum cardiac troponin and brain natriuretic peptide levels were measured by ELISA. The study was approved by the Ethic Committee of General Hospital of Ningxia Medical University in China (approval No. 2018-320). RESULTS AND CONCLUSION: Compared with the control group, the 10-day survival rate of rats in the LPS subgroups was lower. Compared with the control group, there was no reduction in left ventricular ejection fraction and left fractional shortening in the LPS 6-hour group (both P > 0.05). While in the LPS 12-hour group and LPS 24-hour group, the left ventricular ejection fraction and left fractional shortening significantly decreased (all P < 0.01), and the decrease was more obvious with time (all P < 0.01). Compared with the control group, the serum cardiac troponin and brain natriuretic peptide levels were significantly increased in the LPS 12-hour group and LPS 24-hour group (all P < 0.01), and the serum cardiac troponin and brain natriuretic peptide levels gradually increased with LPS injection time (all P < 0.01). The myocardial pathological morphology and ultrastructure of the LPS subgroups showed obvious damage compared with the control group, and the damage was more obvious with the prolongation of LPS injection time. In this experiment, we successfully constructed a stable and reliable model of sepsis-induced myocardial dysfunction in rats, which is an ideal animal model for clinical research of sepsis cardiomyopathy.
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Objective: The present study was to evaluate the feasibility of using the multi-biomarker strategy for the prediction of sepsis-induced myocardial dysfunction (SIMD) and mortality in septic patients. Methods: Brain natriuretic peptide (BNP), cardiac troponin I (cTnI), and heart-type fatty acid-binding protein (h-FABP) in 147 septic patients were assayed within 6 h after admission. We also determined the plasma levels of myeloperoxidase (MPO) and pregnancy-associated plasma protein-A (PAPP-A). The receiver operating characteristic (ROC) curve was used to assess the best cutoff values of various single-biomarkers for the diagnosis of SIMD and the prediction of mortality. Also, the ROC curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) indices were used to evaluate the feasibility of using multi-biomarkers to predict SIMD and mortality. Results: Our statistics revealed that only h-FABP independently predicted SIMD (P0.05). A history of shock and MPO were independent predictors of mortality in septic patients (both P0.05). Conclusions: The findings of this study indicate that a sensitive and specific strategy for early diagnosis of SIMD and mortality prediction in sepsis should incorporate three biomarkers.
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OBJECTIVE@#The present study was to evaluate the feasibility of using the multi-biomarker strategy for the prediction of sepsis-induced myocardial dysfunction (SIMD) and mortality in septic patients.@*METHODS@#Brain natriuretic peptide (BNP), cardiac troponin I (cTnI), and heart-type fatty acid-binding protein (h-FABP) in 147 septic patients were assayed within 6 h after admission. We also determined the plasma levels of myeloperoxidase (MPO) and pregnancy-associated plasma protein-A (PAPP-A). The receiver operating characteristic (ROC) curve was used to assess the best cutoff values of various single-biomarkers for the diagnosis of SIMD and the prediction of mortality. Also, the ROC curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) indices were used to evaluate the feasibility of using multi-biomarkers to predict SIMD and mortality.@*RESULTS@#Our statistics revealed that only h-FABP independently predicted SIMD (P0.05). A history of shock and MPO were independent predictors of mortality in septic patients (both P0.05).@*CONCLUSIONS@#The findings of this study indicate that a sensitive and specific strategy for early diagnosis of SIMD and mortality prediction in sepsis should incorporate three biomarkers.
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A presente revisão tem por objetivo aprimorar o conhecimento sobre Dilated Cardiomyopathy (DCM) em cães, visando à compreensão dos aspectos clínicos, diagnóstico e tratamento. A DCM é caracterizada por dilatação ventricular, disfunção sistólica e arritmias que podem culminar em insuficiência cardíaca e morte. É a segunda cardiopatia mais frequente em cães, acometendo principalmente animais de grande porte e machos. A etiologia é idiopática, mas alguns genes associados à doença já foram identificados. A manifestação clínica é dividida basicamente em estágios oculto e sintomático. O estágio oculto é caracterizado pela presença de alterações elétricas e/ou morfológicas e ausência de sinais clínicos. Os cães podem apresentar o estágio oculto longo até o desenvolvimento de insuficiência cardíaca de forma aguda ou morte súbita. O estágio sintomático é definido pela presença de insuficiência cardíaca esquerda ou biventricular. O diagnóstico somente é confirmado por meio de ecocardiograma e/ou Holter. Estes exames são considerados padrão-ouro, uma vez que apresentam alta sensibilidade na identificação precoce da doença. Cães de raças predispostas devem ser monitorados anualmente a partir dos três anos de idade. O tratamento tem o intuito de minimizar os efeitos da insuficiência cardíaca, sendo instituído de acordo com a fase em que o animal se encontra. O prognóstico após início dos sinais clínicos é desfavorável. Alguns fatores podem influenciar a sobrevida de forma positiva ou negativa. A realização de exames periódicos é de grande importância para obter o diagnóstico precoce e intervir de maneira a retardar a progressão da doença.
The aim of the present review is to improve the knowledge about Cardiomyopathy dilata (CMD) in dogs, in order to understanding clinical aspects, diagnosis and treatment. CMD is characterized by ventricular dilation, systolic dysfunction, and arrhythmias that may culminate in heart failure and death. It is the second most common heart disease in dogs, affecting mainly large animals and males. The etiology is idiopathic, but some genes associated with the disease have already been identified. The clinical manifestation is basically divided into occult and symptomatic stages. The occult stage is characterized by the presence of electrical and/or morphological changes and absence of clinical signs. Dogs may present the long occult stage to the development of acute heart failure or sudden death. The symptomatic stage is defined by the presence of left or biventricular heart failure. The diagnosis is only confirmed by echocardiography and/or Holter. These exams are considered gold standard, since they present high sensitivity in the early identification of the disease. Dogs of predisposed breeds should be monitored annually from the age of three. The treatment is intended to minimize the effects of heart failure, and is instituted according to the stage in which the animal is. The prognosis after onset of clinical signs is worse. Some factors may influence survival in a positive or negative way. Periodic examinations are great importance to obtain early diagnosis and interpose in order to delay the progression of the disease.
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Animals , Dogs , Echocardiography/veterinary , Cardiomyopathy, Dilated/veterinary , Early Diagnosis , Dogs/abnormalities , Heart Diseases/veterinaryABSTRACT
A presente revisão tem por objetivo aprimorar o conhecimento sobre Dilated Cardiomyopathy (DCM) em cães, visando à compreensão dos aspectos clínicos, diagnóstico e tratamento. A DCM é caracterizada por dilatação ventricular, disfunção sistólica e arritmias que podem culminar em insuficiência cardíaca e morte. É a segunda cardiopatia mais frequente em cães, acometendo principalmente animais de grande porte e machos. A etiologia é idiopática, mas alguns genes associados à doença já foram identificados. A manifestação clínica é dividida basicamente em estágios oculto e sintomático. O estágio oculto é caracterizado pela presença de alterações elétricas e/ou morfológicas e ausência de sinais clínicos. Os cães podem apresentar o estágio oculto longo até o desenvolvimento de insuficiência cardíaca de forma aguda ou morte súbita. O estágio sintomático é definido pela presença de insuficiência cardíaca esquerda ou biventricular. O diagnóstico somente é confirmado por meio de ecocardiograma e/ou Holter. Estes exames são considerados padrão-ouro, uma vez que apresentam alta sensibilidade na identificação precoce da doença. Cães de raças predispostas devem ser monitorados anualmente a partir dos três anos de idade. O tratamento tem o intuito de minimizar os efeitos da insuficiência cardíaca, sendo instituído de acordo com a fase em que o animal se encontra. O prognóstico após início dos
The aim of the present review is to improve the knowledge about Cardiomyopathy dilata (CMD) in dogs, in order to understanding clinical aspects, diagnosis and treatment. CMD is characterized by ventricular dilation, systolic dysfunction, and arrhythmias that may culminate in heart failure and death. It is the second most common heart disease in dogs, affecting mainly large animals and males. The etiology is idiopathic, but some genes associated with the disease have already been identified. The clinical manifestation is basically divided into occult and symptomatic stages. The occult stage is characterized by the presence of electrical and/or morphological changes and absence of clinical signs. Dogs may present the long occult stage to the development of acute heart failure or sudden death. The symptomatic stage is defined by the presence of left or biventricular heart failure. The diagnosis is only confirmed by echocardiography and/or Holter. These exams are considered gold standard, since they present high sensitivity in the early identification of the disease. Dogs of predisposed breeds should be monitored annually from the age of three. The treatment is intended to minimize the effects of heart failure, and is instituted according to the stage in which the animal is. The prognosis after onset of clinical signs is worse. Some factors may influence survival in a positive or negative way. Periodic examinations are great importance to obtain early diagnosis and interpose in order to delay the progression of the disease.
Subject(s)
Animals , Dogs , Cardiomyopathy, Dilated/classification , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/veterinary , Dogs/abnormalitiesABSTRACT
Objective@#To investigate the protective effect of carbon monoxide release molecule-2 (CORM-2) on sepsis-induced myocardial dysfunction in rats.@*Methods@#140 healthy male Sprague-Dawley (SD) rats were divided into sham operation (Sham) group, model group, CORM-2 pretreatment group, inactivated carbon monoxide release molecule-2 (iCORM) pretreatment group, and dimethyl sulfoxide (DMSO) control group by random number table, with 28 rats in each group. The rat sepsis model was reproduced by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS). The rats in the Sham group were injected intraperitoneally with the same dose of normal saline (NS). The rats in the CORM-2 and iCORM-2 pretreatment groups were injected intraperitoneally with 8 mg/kg CORM-2 or iCORM-2 at 1 hour before LPS injection, respectively, and those in the DMSO group were injected intraperitoneally with the same dose of DMSO, but the rats in the Sham group and the model group were not treated after injection of NS or LPS. Twenty rats were randomly selected from each group to observe 10-day survival rate. Transthoracic echocardiography was performed on the remaining 8 rats at 12 hours after modeling, and the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were calculated to evaluate heart function. The blood of the inferior vena cava was harvested, then serum myocardial troponin I (cTnI) and brain natriuretic peptide (BNP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Then the rats were sacrificed, and the myocardial tissues were harvested, the pathological morphology and ultrastructure of myocardium were observed.@*Results@#① Survival rates: all rats in the Sham group survived; compared with the Sham group, the survival rates of the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group were significantly decreased at 10 days [10% (2/20), 70% (14/20), 25% (5/20), 15% (3/20) vs. 100% (20/20), all P < 0.01]. However, the 10-day survival rate in the CORM-2 pretreatment group was significantly higher than those in the model group, iCORM-2 pretreatment group and DMSO control group (all P < 0.01). ② Cardiac function: compared with the Sham group, LVEF and LVFS in the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group were significantly decreased, and left ventricular dilatation was obvious, indicating myocardial dysfunction in rats. However, LVEF and LVFS in the CORM-2 pretreatment group were significantly higher than those in the model group, iCORM-2 pretreatment group, and DMSO control group [LVEF: 0.760±0.029 vs. 0.634±0.021, 0.629±0.066, 0.673±0.023; LVFS: (39.32±2.38)% vs. (29.75±1.52)%, (29.61±4.15)%, (32.43±1.66)%, all P < 0.05], and the left ventricular dilatation in the septic rats was attenuated. ③ Myocardial injury markers: compared with the Sham group, serum cTnI and BNP levels were significantly higher in the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group. However, the levels of cTnI and BNP in the CORM-2 pretreatment group were significantly lower than those in the model group, iCORM-2 pretreatment group and DMSO control group [cTnI (ng/L): 3 283.54±803.50 vs. 6 449.18±1 105.10, 5 919.21±1 068.27, 6 349.80±1 153.08; BNP (ng/L): 3 456.62±905.85 vs. 6 070.18±1 287.62, 5 581.13±1 161.17, 5 974.89±988.89, all P < 0.05]. ④ Myocardial histopathological observation: optical microscope showed that the pathological changes in myocardial tissue of the model group, iCORM-2 pretreatment group and DMSO control group were severe. Transmission electron microscopy showed mitochondrial swelling, and some vacuoles changed. But the myocardial pathological morphology and mitochondrial ultrastructural integrity of the CORM-2 pretreatment group were significantly better than other groups of sepsis.@*Conclusion@#CORM-2 can attenuate myocardial dysfunction and improve survival rate of septic rats, especially to protect myocardial mitochondrial integrity in sepsis.
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Objective To investigate the protective effect of carbon monoxide release molecule-2 (CORM-2) on sepsis-induced myocardial dysfunction in rats. Methods 140 healthy male Sprague-Dawley (SD) rats were divided into sham operation (Sham) group, model group, CORM-2 pretreatment group, inactivated carbon monoxide release molecule-2 (iCORM) pretreatment group, and dimethyl sulfoxide (DMSO) control group by random number table, with 28 rats in each group. The rat sepsis model was reproduced by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS). The rats in the Sham group were injected intraperitoneally with the same dose of normal saline (NS). The rats in the CORM-2 and iCORM-2 pretreatment groups were injected intraperitoneally with 8 mg/kg CORM-2 or iCORM-2 at 1 hour before LPS injection, respectively, and those in the DMSO group were injected intraperitoneally with the same dose of DMSO, but the rats in the Sham group and the model group were not treated after injection of NS or LPS. Twenty rats were randomly selected from each group to observe 10-day survival rate. Transthoracic echocardiography was performed on the remaining 8 rats at 12 hours after modeling, and the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were calculated to evaluate heart function. The blood of the inferior vena cava was harvested, then serum myocardial troponin I (cTnI) and brain natriuretic peptide (BNP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Then the rats were sacrificed, and the myocardial tissues were harvested, the pathological morphology and ultrastructure of myocardium were observed. Results ① Survival rates: all rats in the Sham group survived; compared with the Sham group, the survival rates of the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group were significantly decreased at 10 days [10% (2/20), 70% (14/20), 25% (5/20), 15% (3/20) vs. 100% (20/20), all P < 0.01]. However, the 10-day survival rate in the CORM-2 pretreatment group was significantly higher than those in the model group, iCORM-2 pretreatment group and DMSO control group (all P < 0.01). ② Cardiac function: compared with the Sham group, LVEF and LVFS in the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group were significantly decreased, and left ventricular dilatation was obvious, indicating myocardial dysfunction in rats. However, LVEF and LVFS in the CORM-2 pretreatment group were significantly higher than those in the model group, iCORM-2 pretreatment group, and DMSO control group [LVEF: 0.760±0.029 vs. 0.634±0.021, 0.629±0.066, 0.673±0.023; LVFS: (39.32±2.38)% vs. (29.75±1.52)%, (29.61±4.15)%, (32.43±1.66)%, all P < 0.05], and the left ventricular dilatation in the septic rats was attenuated.③ Myocardial injury markers: compared with the Sham group, serum cTnI and BNP levels were significantly higher in the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group. However, the levels of cTnI and BNP in the CORM-2 pretreatment group were significantly lower than those in the model group, iCORM-2 pretreatment group and DMSO control group [cTnI (ng/L): 3 283.54±803.50 vs. 6 449.18±1 105.10, 5 919.21±1 068.27, 6 349.80±1 153.08; BNP (ng/L): 3 456.62±905.85 vs. 6 070.18±1 287.62, 5 581.13±1 161.17, 5 974.89±988.89, all P < 0.05]. ④ Myocardial histopathological observation: optical microscope showed that the pathological changes in myocardial tissue of the model group, iCORM-2 pretreatment group and DMSO control group were severe. Transmission electron microscopy showed mitochondrial swelling, and some vacuoles changed. But the myocardial pathological morphology and mitochondrial ultrastructural integrity of the CORM-2 pretreatment group were significantly better than other groups of sepsis. Conclusion CORM-2 can attenuate myocardial dysfunction and improve survival rate of septic rats, especially to protect myocardial mitochondrial integrity in sepsis.
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Objective To investigate the effect of mild hypothermia on the myocardial and microcirculation dysfunction induced by epinephrine during early post-resuscitation in a rat model of cardiac arrest and cardiopulmonary resuscitation (CPR).Methods Transesophageal cardiac pacing was performed in order to elicit cardiac arrest for 5 min in SD male rats.Totally 40 rats were randomly (random number) divided into 4 groups (n=10):normothermic control group (N),normothermic epinephrine group (N+E),hypothermic control group (H),and hypothermic epinephrine group (H+E).Chest compression was then initiated.Epinephrine (0.02 mg/kg) or saline was administrated at 1 min during CPR.Restoration of spontaneous circulation (ROSC) was recorded,and the rates of ROSC were observed.Myocardial and microcirculatory function were observed at 1,2,3,and 4 h during early post-resuscitation.Serum lactate level was assessed at baseline and ROSC 4 h.Results The ROSC rates were 10/10 in the H+E group,9/10 in the N+E group,4/10 in the H group,and 1/10 in the N group,respectively.Ejection fraction (EF)and cardiac output (CO) in the H+E group were significantly higher than that of other groups (P＜0.05).Total vessel density,perfused vessel density,proportion of perfused vessels,and microvascular flow index in the H+E group were also significantly higher than those of other groups during early post-resuscitation.The serum lactate level in the H+E group was significantly lower than that in the N+E and H groups..Conclusions Both epinephrine and mild hypothermia can improve the success rate of resuscitation.However,mild hypothermia can improve the epinephrine induced myocardial and microcirculatory dysfunction during postresuscitation in the rat cardiac arrest.
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Objective To investigate the characteristics of myocardial injury and its underlying mechanism in rats resuscitated from cardiac arrest. Methods Forty-two male Wistar rats were randomly(random number) assigned into the post-resuscitation (PR) 4 h, PR 24 h, PR 48 h, and sham groups. Ventricular fibrillation was induced by transcutaneous electrical epicardium stimulation and untreated for 6 min, followed by cardiopulmonary resuscitation (CPR). Myocardial function, glucose metabolism, myocardial ultrastructure, the status of mitochondrial permeability transition pore (MPTP) and mitochondrial membrane potential (MMP) were evaluated at different time points. Results Myocardial dysfunction was found at 4 h after restoration of spontaneous circulation (ROSC). The ejection fraction and cardiac output were decreased (all P<0.01), the diastole left ventricular posterior wall became thicker (P<0.01), and the end-diastolic volume was reduced (P<0.05). However, cardiac function was recovered almost completely at 48 h after ROSC. The PR 4 h group had a higher SUVmax, a more obvious decreased absorbance, and a lower MMP than the sham group (all P<0.01), but no statistically significant differences were noted between the PR 48 h group and the sham group (P>0.05). At 4 h and 24 h after ROSC, the mitochondria was swollen and the mitochondrial crista was sparse, but the myocardial ultrastructure was complete. Conclusions Post resuscitation myocardial dysfunction occurs after ROSC and the myocardial dysfunction is completely reversible at 48 h after ROSC, which may be related to the reversibility of myocardial injury and the gradual recovery of mitochondrial structure and function.
ABSTRACT
Sepsis-induced myocardial dysfunction (SIMD) has a high morbidity and mortality, and seriously threatens human health. However, the pathogenesis of the SIMD is still unclear. The previous studies have showed that the SIMD can adversely affect cardiac function through a variety of direct or indirect mechanism, such as autonomic nervous system function damage, pro-inflammatory mediators and activated immune cells induced cardiomyopathy. There is no uniform diagnostic criteria and treatment options. A stable and reliable animal model plays important role in the study that determine the pathogenesis, pathophysiological processes and treatment of SIMD. At present, there are many animal models of cardiac dysfunction caused by sepsis, unfortunately there is no stable, reliable and specific animal model at present. Therefore, it is important to construct a stable and reliable model for studying SIMD. The unified standard of cardiac dysfunction is conducive to the integration and further research. This review focused on pathogenesis of SIMD, routine ways of animal model of SIMD, observation index and basic research to provide references for the researcher to choose the proper animal model.
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Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The early mortality of patients with sepsis-induced myocardial dysfunction (SMD) is higher than those with normal cardiac function, and the long-term prognosis is worse. Therefore, early detection of SMD and timely intervention can reduce mortality and improve prognosis. This review focused on the progress in evaluation and treatment of SMD, with a view to provide some ideas for the diagnosis and treatment of SMD.
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Objective:To observe clinical efficacy of Shengma Biejia Tang combined with Shenfutang on sepsis-induced myocardial dysfunction (SIMD) and study the controlling effect on inflammatory reaction. Method:Eighty-eight patients with SIMD were randomly divided into control group (44 cases) and observation group (44 cases) by random number table. Patients in control group received the early bundle therapy of sepsis, including fluid resuscitation, anti-infection treatment and vasoactive drugs. In addition to the therapy of control group, patients in observation were also given Shengma Biejia Tang combined with Shenfutang, 1 dose/day. And a course of treatment was 7 days. Before and after treatment, levels of troponin (cTnI), creatine kinase isoenzyme (CK-MB), N terminal brain natriuretic precursor (NT-proBNP), calcitonin (PCT), hypersensitivity C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukins-6 (IL-6) and blood lactic acid (LAC) were detected. And color Doppler ultrasound examination of the heart was performed to record left ventricular ejection fraction (LVEF), blood flow velocity of early mitral valve diastole and ratio of blood flow velocity at atrial systolic peak (E/A) and stroke volume (SV). And lactate clearance rate (LCR) was calculated. And sequential (sepsis-related) organ failure assessment (SOFA), acute physiology and chronic health (APACHEⅡ) and traditional Chinese medicine(TCM)syndromes were scored. Result:After treatment, levels of cTnI, NT-ProBNP, CK-MB, Hs-CRP, IL-6, PCT, TNF-α and LAC in observation group were lower than those in control group (PPPConclusion:In addition to the integrated western medicine, Shengma Biejia Tang combined with Shenfutang can control inflammatory reaction, relieve myocardial inhibition and myocardial damage, and protect and improve heart function, and alleviate the symptoms.
ABSTRACT
Abstract Background: Caloric restriction is known to impair the cardiac function and morphology in hypertrophied hearts of spontaneously hypertensive rats (SHR); however, the influence of fasting/refeeding (RF) is unknown. Objective: To investigate the fasting/refeeding approach on myocardial remodeling and function. In addition, the current study was designed to bring information regarding the mechanisms underlying the participation of Ca2+ handling and b-adrenergic system. Methods: Sixty-day-old male SHR rats were submitted to food ad libitum (C), 50% food restriction (R50) or RF cycles for 90 days. Cardiac remodeling was assessed by ultrastructure analysis and isolated papillary muscle function. The level of significance considered was 5% (a = 0.05). Results: The RF rats presented lower cardiac atrophy than R50 in relation to C rats. The C rats increased weight gain, R50 maintained their initial body weight and RF rats increased and decreased weight during RF. The RF did not cause functional impairment because the isotonic and isometric parameters showed similar behavior to those of C. The isotonic and isometric cardiac parameters were significantly elevated in RF rats compared to R50 rats. In addition, the R50 rats had cardiac damage in relation to C for isotonic and isometric variables. While the R50 rats showed focal changes in many muscle fibers, the RF rats displayed mild alterations, such as loss or disorganization of myofibrils. Conclusion: Fasting/refeeding promotes cardiac beneficial effects and attenuates myocardial injury caused by caloric restriction in SHR rats, contributing to reduce the cardiovascular risk profile and morphological injuries. Furthermore, RF promotes mild improvement in Ca2+ handling and b-adrenergic system.
Resumo Fundamento: A restrição calórica compromete a função e a morfologia cardíacas em corações hipertrofiados de ratos espontaneamente hipertensos (SHR). No entanto, a influência de ciclo de jejum/Realimentação é desconhecida. Objetivo: Investigar o efeito de ciclos de jejum/realimentação sobre a remodelação e função miocárdica. Além disso, o presente estudo foi desenhado para avaliar os mecanismos subjacentes à participação do trânsito de cálcio (Ca+2) e sistema beta-adrenérgico. Métodos: Neste estudo, SHR machos de 60 dias de idade foram submetidos a alimento ad libitum (grupo C), 50% de restrição alimentar (grupo R50) ou ciclos de RF (grupo RF) por 90 dias. A remodelação cardíaca foi avaliada por meio da análise ultraestrutural e função do músculo papilar isolado. Adotou-se o nível de significância de 5% (a = 0,05). Resultados: Os ratos do grupo RF apresentaram menor atrofia cardíaca do que os do grupo R50 em relação aos do grupo C. Os ratos do grupo C aumentaram peso corporal, os ratos do grupo R50 mantiveram seu peso corporal inicial e os ratos do grupo RF aumentaram e reduziram seu peso durante o ciclo RF. O ciclo RF não causou comprometimento funcional, pois os parâmetros isotônicos e isométricos apresentaram comportamento similar aos dos ratos do grupo C. Os parâmetros cardíacos isotônicos e isométricos mostraram-se significativamente elevados nos ratos do grupo RF em comparação aos dos ratos do grupo R50. Além disso, os ratos do grupo R50 apresentaram dano cardíaco em comparação aos ratos do grupo C quanto às variáveis isotônicas e isométricas. Os ratos do grupo R50 apresentaram alterações focais em muitas fibras musculares, enquanto os ratos do grupo RF apresentaram leves alterações, como perda ou desorganização de miofibrilas. Conclusão: Ciclos de Jejum/Realimentação promovem efeitos benéficos cardíacos e atenuam o dano miocárdico causado por restrição calórica em SHR, contribuindo para reduzir o risco cardiovascular e os danos morfológicos. Além disso, o ciclo de jejum/realimentação promove leve melhora do trânsito do Ca2+ e do sistema beta-adrenérgico.