Septic Myocardial Depression Research Articles

Use of Levosimendan in Right Ventricular Dysfunction due to Sepsis and Septic Shock: A Research Protocol

Introduction: Sepsis is a clinical condition that results from infection and systemic inflammatory response syndrome, which can progress to severe sepsis and septic shock. This condition leads to myocardial dysfunction and increased mortality rates, particularly in cases of septic shock. Inotropic agents are beneficial in improving cardiac contractility and cardiac output in septic shock. Need for the study: It is important to address myocardial dysfunction in sepsis and septic shock, as these conditions significantly contribute to patient morbidity and mortality. Calcium desensitisation is a key factor in the pathophysiology of septic myocardial depression, leading to impaired cardiac function. Levosimendan, a novel calcium sensitiser, offers a promising therapeutic option due to its unique pharmacologic and biologic profile. By enhancing calcium sensitivity in cardiac myocytes, levosimendan may improve cardiac function without the detrimental side-effects associated with traditional inotropic agents. Aim: The research protocol was planned with an aim to analyse the impact of intravenous levosimendan on Right Ventricular (RV) dysfunction in patients with septic shock. Materials and Methods: This prospective observational study aims to assess the effect of levosimendan on the improvement of RV dysfunction in patients with septic shock who are admitted to the intensive care unit of Acharya Vinoba Bhave Rural Hospital, DMIHER (DU) Sawangi (Meghe), Wardha, Maharashtra, India from July 2023 to March 2025, 45 patients who meet the inclusion criteria will be recruited. Transthoracic Echocardiography (TTE) will be performed using standard measures to calculate RV function. Patients diagnosed with RV dysfunction will be administered levosimendan, followed by a re-evaluation of RV function at designated intervals. Statistical analysis will be conducted using R software, and a paired t-test will be employed to determine significant differences at pre- and post-intervention timelines for the outcome variables of echocardiographic parameters, including Tricuspid Annular Plane Systolic Excursion (TAPSE), EF, RV Fractional Area Change (FAC), and Tricuspid Regurgitant jet Velocity (TRV), at a 5% level of significance.

Progress in the Clinical Assessment and Treatment of Myocardial Depression in Critically Ill Patient with Sepsis.

Myocardial inhibition is the main cause of death in patients with sepsis.In recent years, methodological differences in the diagnosis, assessment, and treatment of septic myocardial depression have been observed, and how to objectively and accurately evaluate the degree of myocardial depression and the timing of treatment strategies have generally been the focus of this area of research. Based on the relevant research at home and abroad, the current review summarizes the clinical characteristics, methodological diagnosis, and symptomatic treatment of septic myocardial depression. The aim of doing so is to provide a reference for the early identification and treatment of patients with sepsis and myocardial depression.

Activation of STIM1/Orai1‑mediated SOCE in sepsis‑induced myocardial depression

Unbalanced Ca2+ homeostasis serves an essential role in the occurrence and development of septic myocardial injury. However, the mechanism of Ca2+ homeostasis in septic myocardial depression is poorly understood due to the complexity of Ca2+ transporters in excitable cells. It was therefore hypothesized that cardiac dysfunction, myocardial injury and cardiac apoptosis in septic myocardial depression are associated with elevated intracellular Ca2+ concentrations caused by stromal interaction molecule 1 (STIM1)/Orai calcium release‑activated calcium modulator 1 (Orai1)‑mediated store‑operated Ca2+ entry (SOCE). A septic myocardial depression model was established using the cecal ligation and puncture operation (CLP) in mice and was simulated in H9C2 cells via lipopolysaccharide (LPS) stimulation. Cardiac function, myocardial injury, cardiac apoptosis and the expression levels of Bax, Bcl‑2, STIM1 and Orai1 were quantified invivo at6, 12and24h. Changes in the intracellular Ca2+ concentration, SOCE and the distribution of STIM1 were assessed invitro within 6h. The morphological changes of heart tissue were observed by hematoxylin‑eosin staining. Myocardial cellular apoptosis was determined by TUNEL method. The expression of Bax, Bcl‑2, STIM1 and Orai1 were visualized by western blot. Cytosolic calcium concentration and SOCE were evaluated by confocal microscopy. The results demonstrated that cardiac contractile function was significantly reduced at6h and morphological changes in cardiac tissues, as well as the myocardial apoptosis rate, were markedly increased at6, 12and24h following CLP. mRNA and protein expression levels of Bax/Bcl‑2 were significantly enhanced at6and12h and glycosylation of Orai1 in the myocardium of septic mice was significantly increased at6h following CLP. The intracellular Ca2+ concentration, SOCE, was significantly increased at1‑2h and the clustering and distribution of STIM1 were markedly changed in H9C2 cells at1and2h. These findings suggested that myocardial dysfunction, cardiac injury and myocardial depression may be related to increased intracellular Ca2+ concentration resulting from STIM1/Orai1‑mediated SOCE, which may provide a potential method to alleviate septic myocardial depression.

Exosome-Derived From Sepsis Patients' Blood Promoted Pyroptosis of Cardiomyocytes by Regulating miR-885-5p/HMBOX1.

BackgroundSeptic myocardial depression has been associated with increased morbidity and mortality. miR-885-5p has been shown to regulate cell growth, senescence, and/or apoptosis. Published studies demonstrated that Homeobox-containing protein 1 (HMBOX1) inhibits inflammatory response, regulates cell autophagy, and apoptosis. However, the role of miR-885-5p/HMBOX1 in sepsis and septic myocardial depression and the underlying mechanism is not fully understood.Materials and MethodsExosomes (exos) derived from sepsis patients (sepsis-exos) were isolated using ultracentrifugation. Rats were subjected to cecal ligation and puncture surgery and treated with sepsis-exos. HMBOX1 was knocked down or overexpressed in AC16 cells using lentiviral plasmids carrying short interfering RNAs targeting human HMBOX1 or carrying HMBOX1 cDNA. Cell pyroptosis was measured by flow cytometry. The secretion of IL-1β and IL-18 was examined by ELISA kits. Quantitative polymerase chain reaction (PCR) or western blot was used for gene expression.ResultsSepsis-exos increased the level of miR-885-5p, decreased HMBOX1, elevated IL-1β and IL-18, and promoted pyroptosis in AC16 cells. Septic rats treated with sepsis-exos increased the serum inflammatory cytokines is associated with increased pyroptosis-related proteins of hearts. MiR-885-5p bound to the three prime untranslated regions of HMBOX1 to negatively regulate its expression. Overexpressing HMBOX1 reversed miR-885-5p-induced elevation of inflammatory cytokines and upregulation of NLRP3, caspase-1, and GSDMD-N in AC16 cells. The mechanistic study indicated that the effect of HMBOX1 was NF-κB dependent.ConclusionSepsis-exos promoted the pyroptosis of AC16 cells through miR-885-5p via HMBOX1. The results show the significance of the miR-885-5p/HMBOX1 axis in myocardial cell pyroptosis and provide new directions for the treatment of septic myocardial depression.

Exosomes derived from the blood of patients with sepsis regulate apoptosis and aerobic glycolysis in human myocardial cells via the hsa‑miR‑1262/SLC2A1 signaling pathway.

Myocardial injury occurs in the majority of patients with sepsis and is associated with early mortality. MicroRNAs (miRs) transported by exosomes have been implicated in numerous diseases, such as tumors, acute myocardial infarction and cardiovascular disease. Human serum albumin (hsa)‑miR‑1262 has been shown to serve a role in sepsis; however, its role in exosomes isolated from patients with sepsis and septic myocardial injury remains unclear. In the present study, serum exosomes were isolated via ultracentrifugation. Solute carrier family2 member1 (SLC2A1), an essential mediator in energy metabolism, was silenced and overexpressed in the human myocardial AC16 cell line using lentiviral plasmids containing either SLC2A1‑targeting short interfering RNAs or SLC2A1 cDNA, respectively. Cell apoptosis was analyzed using flow cytometry, and the extracellular acidification rate and oxygen consumption rate of AC16 cells were determined using an XFe24 Extracellular Flux Analyzer. Furthermore, the dual‑luciferase reporter assay was used to evaluate the interaction between hsa‑miR‑1262 and SLC2A1. Finally, reverse transcription‑quantitative PCR and western blotting were used to evaluate gene and protein expression levels, respectively. Exosomes isolated from the blood of patients with sepsis (Sepsis‑exo) markedly reduced aerobic glycolysis activity, but significantly promoted the apoptosis of human AC16 cells in a time‑dependent manner. Moreover, Sepsis‑exo significantly increased hsa‑miR‑1262 expression levels, but significantly decreased SLC2A1 mRNA expression levels in a time‑dependent manner. Bioinformatics analysis indicated that hsa‑miR‑1262 bound to the 3'untranslated region of SLC2A1 to negatively regulate its expression. The silencing of SLC2A1 promoted apoptosis and suppressed glycolysis in AC16 cells, whereas SLC2A1 overexpression resulted in the opposite effects. Therefore, the present study demonstrated that exosomes derived from patients with sepsis may inhibit glycolysis and promote the apoptosis of human myocardial cells through exosomal hsa‑miR‑1262 via its target SLC2A1. These findings highlighted the importance of the hsa‑miR‑1262/SLC2A1 signaling pathway in septic myocardial injury and provided novel insights into therapeutic strategies for septic myocardial depression.

Effect of Glucose-Insulin-Potassium Infusion on Hemodynamics in Patients with Septic Shock

BACKGROUND: Glucose-insulin-potassium (GIK) demonstrates a cardioprotective effect by providing metabolic support and anti-inflammatory action, and may be useful in septic myocardial depression. AIM: The aim of this study was to assess role of GIK infusion in improving hemodynamics in patients with septic shock in addition to its role in myocardial protection and preventing occurrence of sepsis-induced myocardial dysfunction and sepsis-induced arrhythmias. METHODS: This study was conducted on 75 patients admitted to the Critical Care Department in Cairo University Hospital with the diagnosis of septic shock during the period from January 2019 to December 2019. Patients were divided into two groups; first group was managed according to the last guidelines of surviving sepsis campaign and was subjected to the GIK infusion protocol while second group was managed following the last guidelines of surviving sepsis campaign only without adding GIK infusion. RESULTS: Patients in the GIK group showed better lactate clearance (50% vs. 46.7%) and less time needed for successful weaning of vasopressors than the control group (3.57±1.16 vs. 3.6±1.45 days) thought not reaching statistical significance. There was no statistically significant difference between both groups regarding development of septic-induced cardiomyopathy (16.7% in the control group vs. 13.3% in the GIK group); however, patients with hypodynamic septic shock showed better improvement in hemodynamic profile in the GIK group. Sepsis-induced arrhythmias occurred more in patients of the control group than in patients of the GIK group with no statistically significant difference between both groups (33.3% vs. 20%, p = 0.243). Few side effects were developed as a result of using GIK infusion protocol. CONCLUSIONS: GIK may help in improving hemodynamics and weaning of vasopressors in patients with refractory septic shock and those with septic induced cardiomyopathy. The use of GIK was well tolerated with minimal adverse reactions.

Evaluation of the safety and efficacy of beta blockers in septic patients: a randomized control trial

BackgroundSepsis is a common fatal complication of an infection. As part of the host response, sympathetic stimulation can result in many serious complications such as septic myocardial depression and metabolic, hematological, and immunological dysfunction. Treatment with beta blockers may reduce this pathophysiological response to infection, but the clinical outcomes are not clear.ResultsOur study showed a significant difference as regards decrease in heart rate in group B with P value < 0.001 compared to group A, besides a reduction in 28-day mortality (P value 0.0385) and ICU stay (P value < 0.001) in group B compared to group A.ConclusionThis study supports the role of intravenous beta blockers in sepsis patients by decreasing heart rate without affecting the hemodynamics, in addition to decreasing 28-day mortality and ICU stay.

A case report of iatrogenic gas gangrene post colonoscopy successfully treated with conservative management- is surgery always necessary?

BackgroundColonoscopy is a routine procedure in diagnosis and treatment of colonic disease. While generally regarded as a safe procedure, potentially fatal complications can occur. Gas gangrene is one such complication, with very high mortality. There are few cases of gas gangrene occurring after colonoscopy, making it one of the rarer complications of this procedure. There have been no previously reported cases of a patient surviving such an infection and the optimal treatment strategy is contentious. This report describes a case of intramural gas gangrene of the colon, treated conservatively with antibiotic therapy in which the patient survived with full recovery.Case presentationA 71-year-old, previously healthy male presented 6 h post apparently uncomplicated colonoscopic polypectomy with rigors, nausea, vomiting and right upper quadrant pain. At presentation he was febrile at 40.1 °C but hemodynamically stable. Abdominal computed tomography revealed substantial colonic thickening and several focal intramural gas bubbles (pneumatosis intestinalis) surrounding the polypectomy site. Within 24 h post procedure he became hypotensive and was admitted to ICU in frank septic shock requiring inotropes, and with demonstrable septic myocardial depression. Bloods showed multi-organ derangement with leukocytosis, lactic acidosis, haemolytic anaemia and hyperbilirubinemia. A diagnosis of presumed Clostridial gas gangrene was made, and treatment was initiated with benzylpenicillin, clindamycin, metronidazole and vancomycin. After 4 days in ICU he was stepped down, and discharged after a further 10 days with no surgical or endoscopic interventions. At three-month review he reported being back to full health.ConclusionsThis case demonstrates that gas gangrene infection is a possible complication of colonoscopic polypectomy. This is a cause of rapid deterioration in post-colonoscopy patients and has been misdiagnosed as colonic perforation in previously reported cases of retroperitoneal gas gangrene. Such misdiagnosis delays antibiotic therapy, which likely plays a role in the high mortality of this condition. Early diagnosis and initiation of antibiotic therapy with benzylpenicillin and clindamycin as seen in this case is essential for patient survival. While surgery is typically performed, non-operative management of pneumatosis intestinalis, and potentially gas gangrene is becoming more common and was utilized effectively in this patient.

Characterization of Circular RNA and microRNA Profiles in Septic Myocardial Depression: a Lipopolysaccharide-Induced Rat Septic Shock Model.

Septic shock with heart dysfunction is common in intensive care units. However, the mechanism underlying myocardial depression is still unclear. Whether circular RNA (circRNA) or microRNA (miRNA) profiles differ between patients with and without myocardial depression is unknown. We generated a hypodynamic septic shock model induced by lipopolysaccharide (LPS) in adolescent rats. A total of 12 rats were utilized and heart tissue from each was collected. RNA sequencing was performed on left ventricular tissue. We focused on features of circRNAs and miRNAs, predicting their function by bioinformatic analysis and constructing circRNA-associated and miRNA-associated regulatory networks in heart tissue. We detected 851 circRNAs in heart samples, and 11 showed differential expression. A total of 639 annotated miRNAs and 91 novel miRNAs were explored including 78 showing differential expression between the two groups. We then constructed the most comprehensive circRNA-associated and miRNA-associated networks to explore their regulatory relationship in septic heart tissue, and demonstrated that different networks could potentially participate in and regulate the pathological process of sepsis. Furthermore, gene ontology term enrichment indicated miRNAs, and miRNA-mRNA networks could be associated with regulation and metabolic process, or influence cellular functions. The construction of regulator networks could improve the understanding of the basic molecular mechanisms underlying myocardial depression. It will be important for future investigations to ascertain the biological mechanisms present during the development of sepsis-induced myocardial depression to influence approaches to treatment.

Construction of death early-warning model for patients with septic myocardial depression: a retrospective analysis of 129 patients

To explore the death risk factors of septic myocardial depression (SMD) and their predictive effect, and to set up a death early-warning model. A retrospective analysis was conducted. The patients with SMD admitted to emergency department and rescue room of Beilun Branch of the First Affiliated Hospital of Zhejiang University Medical College from January 2015 to November 2017 were enrolled. The patients were divided into survival group and non-survival group according to 28-day outcome, and the gender, age, and the initial examination parameters [white blood cell (WBC) count, neutrophil (Neut) count, activated partial thromboplastin time (APTT), procalcitonin (PCT), D-dimer, C-reactive protein (CRP), cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and left atrium diameter (LAD)] of both groups were compared. Binary logistic regression analysis was conducted on the factors with statistically significant difference analyzed in univariate analysis, and death early-warning model was set up subsequently. For parameters in early-warning model after variable screening, receiver operating characteristic curve (ROC) was applied to evaluate the predictive effect of death. A total of 129 patients were enrolled, 34 patients died within 28 days with the mortality of 26.4%. Univariate analysis showed that the PCT, cTnI and NT-proBNP in non-survival group were significantly higher than those of the survival group. However, there was no statistical difference in gender, age, WBC, Neut, APTT, D-dimer, CRP, LVEF, LVEDD or LAD between the two groups. Logistic stepwise regression analysis showed that PCT and cTnI were the independent factors influencing the death of patients with SMD [PCT: odds ratio (OR) =1.495, 95% confidence interval (95%CI) = 1.192-1.876, P = 0.001; cTnI: OR = 11.154, 95%CI = 5.709-17.264, P = 0.004], and the death early-warning model was logP = -3.737+0.402×PCT+2.412×cTnI. According to the statistics of Homser-Lemeshow, the effect of this model was good (χ2 = 6.258, P = 0.617). The analysis of ROC displayed that the area under ROC curve (AUC) of the combination of PCT and cTnI for predicting the prognosis of SMD patients was 0.851, and it was significantly higher than that of PCT and cTnI alone (0.738 and 0.719, respectively, both P < 0.05). When the combination of PCT and cTnI was 0.26, the sensitivity was 79.97%, the specificity was 87.01%, the positive predictive value was 71.3%, and the negative predictive value was 91.7%. PCT and cTnI are independent factors influencing the death of SMD patients. The combination of PCT and cTnI has predictive value for the prognosis of SMD patients. The death early-warning model of SMD patients can be used to predict the prognosis of SMD patients.

The Trend of β3-Adrenergic Receptor in the Development of Septic Myocardial Depression: A Lipopolysaccharide-Induced Rat Septic Shock Model

Septic shock with low cardiac output is very common in children. However, the mechanism underlying myocardial depression is unclear. The role of β₃-AR in the development of myocardial depression in sepsis is unknown. In the present study, we generated an adolescent rat model of hypodynamic septic shock induced by lipopolysaccharide (LPS). Neonatal cardiomyocytes were also treated with LPS to mimic myocardial depression in sepsis, which was confirmed via an in vivo left ventricular hemodynamic study, and measurements of contractility and the Ca²⁺ transient in isolated adolescent and neonatal cardiomyocytes. After 16 h of LPS treatment, cultured neonatal cardiomyocytes showed a diminished Ca²⁺ transient amplitude associated with an increase in the β₃-AR level. With the addition of a β₃-AR agonist, the Ca²⁺ transient in LPS-treated neonatal rat cardiomyocytes gradually decreased over time; such a change was absent in cells treated with nitric oxide synthase (NOS) inhibitors prior to treatment with a β₃-AR agonist. In adolescent rats with septic myocardial depression, cardiac function declined as indicated by decreased MAP, dP/dt_max, and dP/dt_mix for 6 h after LPS injection; however, the β₃-AR level first increased 2 h after LPS treatment and then decreased 6 h after LPS treatment in the absence of exogenous catecholamines. The results indicate that, in vitro, at the cellular level β₃-AR may be involved in the development of myocardial depression (Ca²⁺ transient depression) in sepsis through NOS signaling pathways; however, in vivo, a complicated mechanism for modulating β₃-AR may exist.

The β-Blocker Esmolol Restores the Vascular Waterfall Phenomenon After Acute Endotoxemia*

A vascular waterfall occurs when the critical closing pressure is greater than the mean systemic filling pressure. Because the waterfall phenomenon likely exists in the microcirculation, β1-receptor blockers such as esmolol could have some effect on microcirculation and vascular waterfall. To determine whether a vascular waterfall exists during septic shock and to assess the effects of vasopressors and β-blockers on vascular waterfall. Sixteen mongrel dogs were mounted with ultrasonic flow probes to measure renal blood flow. The hemodynamic variables of 16 animals were measured at baseline, after induction of acute endotoxemia; then, they underwent volume expansion, and norepinephrine was used to achieve baseline. After achieving septic myocardial depression, the animals were randomly divided into two groups (esmolol vs control groups) after reaching septic myocardial depression. There was a pressure gap of 41.9 ± 13.9 mm Hg between the arterial critical closing pressure and the mean systemic filling pressure, indicating that a vascular waterfall was present under baseline conditions. Endotoxemia caused a decrease in cardiac output, mean arterial pressure, and critical closing pressure. Endotoxemia also caused the vascular waterfall to disappear. Neither volume expansion nor norepinephrine had any effect on the vascular waterfall. Esmolol infusion restored the vascular waterfall effect following endotoxemia and resuscitation. The 24-hour survival was 75% in the esmolol group versus 12.5% in controls (p = 0.041). Vascular pressure gradients in renal vasculature suggest the presence of a vascular waterfall at baseline. Although this phenomenon disappeared in endotoxemic dogs, it could be restored with β-blocker therapy (esmolol).

The predictive value of serum presepsin (sCD14-ST) for myocardial depression in septic patients

Objective To evaluate the predictive value of serum presepsin (sCD14-ST) for septic myocardial depression (SMD) in patients with severe sepsis or septic shock. Methods This was a prospective cohort study. A total of 84 patients with severe sepsis or septic shock were monitored by pulse indicator continuous cardiac output (PiCCO) system and divided into myocardial depression group (cardiac function index [CFI] <4.1 L/min, n=37) and non-myocardial depression group (CFI≥4.1 L/min, n=47) according to cardiac function index (CFI). Left ventricular ejection fraction (LVEF) was measured by doppler echocardiography at admission. The patients were divided into survival group (n=40) and non-survival group (n=44) based on 28-day mortality. Serum sCD14-ST, B-type natriuretic peptide(BNP), tumor necrosis factor-α(TNF-α), cardiac troponin Ⅰ (cTnⅠ) levels and hemodynamic parameters were observed dynamically at day 1, 3, 5 after admission. Quantitative data with normal distribution were analyzed using t-test and abnormal distribution data were analyzed using Mann-Whitney U test. Categorical data were analyzed using χ2 test. Results The serum levels of cardiac index (CI), global ejection fraction (GEF) and left ventricular contractility index (dPmax) in myocardial depression group were all significantly lower than those in non-depression group at day 1 after admission (all P 0.05). There were 24 cases died in myocardial depression group. The mortality of myocardial depression group was significantly higher than that of non-depression group (64.9% vs 42.6%, χ2= 4.132, P = 0.042). The serum levels of sCD14-ST at day 1 and day 3 in myocardial depression group were significantly higher than those in non-myocardial depression group (both P<0.01). sCD14-ST levels in both groups showed downtrend. The serum level of sCD14-ST in non-survival group was significantly higher than that in survival group (P<0.01). Conclusions Myocardial depression is common in patients with severe sepsis and septic shock. High serum level of sCD14-ST is correlated with myocardial depression to some extent, but not an independent predictor. The combination of sCD4-ST, BNP and TNF-α can improve the predictive value for myocardial depression. Key words: Sepsis; sCD14-ST; Tumor necrosis factor-alpha; BNP

Glucose-insulin-potassium correlates with hemodynamic improvement in patients with septic myocardial dysfunction.

Glucose-insulin-potassium (GIK) demonstrates a cardioprotective effect by providing metabolic support and anti-inflammatory action, and may be useful in septic myocardial depression. The aim of this study was to examine the relationship between GIK and hemodynamic outcomes in septic shock patients with myocardial depression. Between October 2012 and March 2014, 45 patients in the intensive care unit who fulfilled the criteria for severe sepsis/septic shock and were treated with GIK were recruited. Patients were divided into two groups according to echocardiographic findings: hypodynamic (27%) and non-hypodynamic (36%). Baseline vasopressor requirements did not differ between both groups. In 12 patients with hypodynamic septic shock with myocardial depression, mean arterial pressure (MAP) increased with the median [interquartile range (IQR)] area under the curve of 16 (8 to 29) mmHg, and the heart rate (HR) decreased with the median (IQR) area under the curve of -9 (-20 to 2)/min during the first 72 h. The total insulin dose correlated with improvement in MAP (r=0.61, P=0.061) and the cardiovascular Sequential Organ Failure Assessment score (r=-0.64, P=0.045) at 72 h, although this phenomenon was not observed in patients with non-hypodynamic septic shock. Serum glucose and potassium levels were within the target ranges in both groups during the 72-h study period. Short-term improvement in hemodynamics correlated with GIK administration in septic shock patients with myocardial depression. The use of GIK was well tolerated in all patients. Further studies are required to demonstrate the role of GIK in septic myocardial dysfunction.

Beta-blockers in patients with septic shock: plenty of promise, but no hard evidence yet.

Septic myocardial depression, or septic cardiomyopathy, can be defined as a global (that is, affecting systolic and diastolic pressure), but reversible, dysfunction of both the left and right sides of the heart in septic shock (1). The pathogenesis of septic myocardial depression involves a complex interaction between genetic, molecular (including calcium channels, nitric oxide, endothelin-1, cytokines, and toll-like receptors), metabolic (including mitochondrial dysfunction and oxidative stress), autonomic, and hemodynamic variables (2-7).

The role of mitochondrial permeability transition pore in the occurrence of septic myocardial depression

Sepsis is defined as life-threatening organ dysfunction caused by a dys-regulated host response to infection and septic myocardial depression (SMD) is a common complication. Pathogenesis of SMD is complicated and there is lack of specific treatment. Mitochondrial damage is an important pathological basis of SMD, and mitochondrial permeability transition pore (MPTP) plays an important role in maintaining the normal structure and function of the mitochondria. The change of MPTP during sepsis is summarized in this review so as to reveal the significant mechanism of MPTP in the occurrence of SMD.

Research status on pathogenesis of myocardial depression in sepsis

The cardiovascular system plays a key role in sepsis, and septic myocardial depression is a common finding associated with increased morbidity and mortality.Myocardial depression during sepsis is not clearly defined, but it can perhaps be best described as a global (systolic and diastolic) dysfunction of both the left and right sides of the heart.The pathogenesis of septic myocardial depression involves a complex mix factor of genetic, molecular, metabolic, and structural.Now, the research status on pathogenesis of myocardial depress in sepsis was reviewed. Key words: Myocardial depression; Dysfunction of heart; Sepsis; Septic shock

β-Blockers in sepsis: protocol for a systematic review and meta-analysis of randomised control trials

IntroductionSepsis is a common and deadly complication of infection. As part of the host response, sympathetic stimulation can result in septic myocardial depression, and metabolic, haematological and immunological dysfunction. Administration...

Clinical Management of the Cardiovascular Failure in Sepsis

Cardiovascular failure in sepsis involves a combination of hypovolemia, decreased vascular tone, myocardial depression and microcirculatory alterations. Fluids represent the first line therapeutic intervention, with controversy regarding the type of fluid. Recent data indicate that albumin is safe and might even be beneficial in specific subgroups. Starches may be an alternative, although concerns exist on potential detrimental effects on renal function of old generation starches. Trials testing new generation starches are ongoing. When fluids fail to correct hypotension, vasopressor agents are used. Various adrenergic agents increase blood pressure, especially dopamine, noradrenaline and adrenaline, by stimulating alpha-adrenergic receptors. They also variably stimulate beta-adrenergic receptors, increasing cardiac contractility, heart rate, and splanchnic perfusion, but with increased risk of arrhythmias, immunomodulation and increased metabolism. Furthermore, dopamine stimulates dopaminergic receptors, resulting in doubtful effects on splanchnic and renal perfusion, but also in endocrine alterations. Do these pharmacologic differences among the various alpha-adrenergic agents translate into clinical differences? Several randomized trials tested the effects of these agents on outcome. Epinephrine produces more undesired effects than norepinephrine, but no clear cut differences on outcome were observed in underpowered trials. Norepinephrine should be preferred over dopamine, as suggested in one large trial and confirmed in a meta-analysis. Vasopressin may be considered as an alternative or in addition to adrenergic agents. In one large trial, no significant difference in outcome was observed, and the exact role of vasopressin still needs clarification. Finally, various inotropic agents can counteract septic myocardial depression. So far, no study supports their routine use, but these may be justified on an individual basis.

Clinical Management of the Cardiovascular Failure in Sepsis

Cardiovascular failure in sepsis involves a combination of hypovolemia, decreased vascular tone, myocardial depression and microcirculatory alterations. Fluids represent the first line therapeutic intervention, with controversy regarding the type of fluid. Recent data indicate that albumin is safe and might even be beneficial in specific subgroups. Starches may be an alternative, although concerns exist on potential detrimental effects on renal function of old generation starches. Trials testing new generation starches are ongoing. When fluids fail to correct hypotension, vasopressor agents are used. Various adrenergic agents increase blood pressure, especially dopamine, noradrenaline and adrenaline, by stimulating alpha-adrenergic receptors. They also variably stimulate beta-adrenergic receptors, increasing cardiac contractility, heart rate, and splanchnic perfusion, but with increased risk of arrhythmias, immunomodulation and increased metabolism. Furthermore, dopamine stimulates dopaminergic receptors, resulting in doubtful effects on splanchnic and renal perfusion, but also in endocrine alterations. Do these pharmacologic differences among the various alpha-adrenergic agents translate into clinical differences? Several randomized trials tested the effects of these agents on outcome. Epinephrine produces more undesired effects than norepinephrine, but no clear cut differences on outcome were observed in underpowered trials. Norepinephrine should be preferred over dopamine, as suggested in one large trial and confirmed in a meta-analysis. Vasopressin may be considered as an alternative or in addition to adrenergic agents. In one large trial, no significant difference in outcome was observed, and the exact role of vasopressin still needs clarification. Finally, various inotropic agents can counteract septic myocardial depression. So far, no study supports their routine use, but these may be justified on an individual basis.