Oxidative Stress, Kinase Activity and Inflammatory Implications in Right Ventricular Hypertrophy and Heart Failure under Hypobaric Hypoxia.

High altitude (hypobaric hypoxia) triggers several mechanisms to compensate for the decrease in oxygen bioavailability. One of them is pulmonary artery vasoconstriction and its subsequent pulmonary arterial remodeling. These changes can lead to pulmonary hypertension and the development of right ventricular hypertrophy (RVH), right heart failure (RHF) and, ultimately to death. The aim of this review is to describe the most recent molecular pathways involved in the above conditions under this type of hypobaric hypoxia, including oxidative stress, inflammation, protein kinases activation and fibrosis, and the current therapeutic approaches for these conditions. This review also includes the current knowledge of long-term chronic intermittent hypobaric hypoxia. Furthermore, this review highlights the signaling pathways related to oxidative stress (Nox-derived O2.- and H2O2), protein kinase (ERK5, p38α and PKCα) activation, inflammatory molecules (IL-1ß, IL-6, TNF-α and NF-kB) and hypoxia condition (HIF-1α). On the other hand, recent therapeutic approaches have focused on abolishing hypoxia-induced RVH and RHF via attenuation of oxidative stress and inflammatory (IL-1ß, MCP-1, SDF-1 and CXCR-4) pathways through phytotherapy and pharmacological trials. Nevertheless, further studies are necessary.

Myeloid-Derived Suppressor Cells Mediate Immunosuppression After Cardiopulmonary Bypass.

OBJECTIVES: Cardiopulmonary bypass is associated with severe immune dysfunctions. Particularly, a cardiopulmonary bypass-related long-lasting immunosuppressive state predisposes patients to a higher risk of postoperative complications, such as persistent bacterial infections. This study was conducted to elucidate mechanisms of post-cardiopulmonary bypass immunosuppression. DESIGN: In vitro studies with human peripheral blood mononuclear cells. SETTING: Cardiosurgical ICU, University Research Laboratory. PATIENTS: Seventy-one patients undergoing cardiac surgery with cardiopulmonary bypass (enrolled May 2017 to August 2018). INTERVENTIONS: Peripheral blood mononuclear cells before and after cardiopulmonary bypass were analyzed for the expression of immunomodulatory cell markers by real-time quantitative reverse transcription polymerase chain reaction. T cell effector functions were determined by enzyme-linked immunosorbent assay, carboxyfluorescein succinimidyl ester staining, and cytotoxicity assays. Expression of cell surface markers was assessed by flow cytometry. CD15 cells were depleted by microbead separation. Serum arginine was measured by mass spectrometry. Patient peripheral blood mononuclear cells were incubated in different arginine concentrations, and T cell functions were tested. MEASUREMENTS AND MAIN RESULTS: After cardiopulmonary bypass, peripheral blood mononuclear cells exhibited significantly reduced levels of costimulatory receptors (inducible T-cell costimulator, interleukin 7 receptor), whereas inhibitory receptors (programmed cell death protein 1 and programmed cell death 1 ligand 1) were induced. T cell effector functions (interferon γ secretion, proliferation, and CD8-specific cell lysis) were markedly repressed. In 66 of 71 patients, a not yet described cell population was found, which could be characterized as myeloid-derived suppressor cells. Myeloid-derived suppressor cells are known to impair immune cell functions by expression of the arginine-degrading enzyme arginase-1. Accordingly, we found dramatically increased arginase-1 levels in post-cardiopulmonary bypass peripheral blood mononuclear cells, whereas serum arginine levels were significantly reduced. Depletion of myeloid-derived suppressor cells from post-cardiopulmonary bypass peripheral blood mononuclear cells remarkably improved T cell effector function in vitro. Additionally, in vitro supplementation of arginine enhanced T cell immunocompetence. CONCLUSIONS: Cardiopulmonary bypass strongly impairs the adaptive immune system by triggering the accumulation of myeloid-derived suppressor cells. These myeloid-derived suppressor cells induce an immunosuppressive T cell phenotype by increasing serum arginine breakdown. Supplementation with L-arginine may be an effective measure to counteract the onset of immunoparalysis in the setting of cardiopulmonary bypass.

Modifying Effect of Autotransfusion of Mesenchymal Stromal Cells on the Production of Reactive Oxygen Species and Cytokines by Mononuclear Cells in Patients with Chronic Heart Failure.

We studied in vivo modifying effect of autotransfusion of human bone marrow mesenchymal stromal cells on ROS generation and production of cytokines (TNFα,TNFß, IL-1α, IL-10, IFNγ, and GM-CSF) and PGE2 by mononuclear cells of patients (N=21) with chronic heart failure. These parameters were evaluated prior to (control) and after (immediately and on day 14) intravenous administration of stromal cells in doses of 100-200×106. Immediately after autotransfusion, significant increase of in vitro zymosan-induced chemiluminescence of blood mononuclear cells from 10 patients was observed. At later terms after autotransfusion (day 14), inhibition of chemiluminescent activity of blood mononuclear cells was revealed in 50% patients. We discuss possible mechanisms of involvement of transplanted autologous bone marrow mesenchymal stromal cells in reprogramming of blood mononuclear phagocytes from the pro- to anti-inflammatory phenotype under conditions of their in vivo interaction manifesting in transition from activation to inhibition of ROS-producing activity of macrophages and significant suppression of in vitro LPS-induced production of TNFα and GM-CSF by blood mononuclears against the background of significantly elevated TNFß, IL-10, and IL-1α concentrations.

Vitamin D deficiency contributes to the reduction and impaired function of naïve CD45RA⁺ regulatory T cell in chronic heart failure.

The effect of vitamin D pertinent to cardiovascular health on the heart itself is considered to shift toward an anti-inflammatory response in chronic heart failure (CHF); however, its underlying mechanism is not completely understood. In this study, we demonstrated that plasma 25(OH)D level, negatively associated with NT-ProBNP, correlated with the decreased Treg in CHF compared to the patients with other cardiovascular diseases and healthy and older donors. Naïve Treg cell (CD4(+)CD45RA(+)Foxp3(lo)T) subset, rather than whole Treg cells, contributes to the reduction of Treg in CHF. 1,25(OH)2D treatment maintained partial expression of CD45RA on CD4(+)T cell after αCD3/CD28 monoclonal antibodies activation and ameliorated the impaired CD4(+)CD45RA(+)T cell function from CHF patients through upregulating Foxp3 expression and IL-10 secretion in vitro. Low level of vitamin D receptor (VDR) was detected in CD4(+)CD45RA(+)T cell of CHF than control, while 1,25(OH)2D treatment increased the VDR expression to exert its immunosuppression on T cell. The results of this study might provide tangible evidence to our knowledge of the impact of vitamin D supplementation on naïve Tregs, which may offer new means of preventing and treating CHF.

Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats.

This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

[Antibodies to Hsp60 in newborn babies, to whom during the intervention for critical inborn heart failure, autologous cord blood was transfused, in early and late postoperative period].

The titre of antibodies to Hsp60 (heat shock protein) enhancement in the blood serum is considered a biological marker of poor state of organism. Comparative investigation was done on the antibodies titre to Hsp60 in the blood serum of a newborn babies, suffering critical inborn heart failure, to whom autologous cord blood or the donor's blood components was transfused, in early and remote postoperative period. In early postoperative period the lowering of the antibodies titre to Hsp60 in the blood serum was observed in comparison with them preoperatively, in a late period (in 2 yrs) in all the blood serum samples investigated antibodies to Hsp60 were not revealed. In 35% of patients, to whom the donor's blood components were transfused, there was registered the enhancement of the antibodies to Hsp60 titre in early postoperative period. High titre of antibodies have associated with enhanced rate of complications. In late postoperative period antibodies to Hsp60 were revealed in 20% of the examined patients.

Hyperthermia by bathing in a hot spring improves cardiovascular functions and reduces the production of inflammatory cytokines in patients with chronic heart failure.

Balneotherapy has been shown to reduce systemic blood pressure in healthy volunteers. Hyperthermia might ameliorate the inflammatory status in heart failure through improving cardiac function. The purpose of this study was to examine the beneficial effects of balneotherapy in patients with chronic heart failure (CHF). Thirty-two patients with systolic CHF classified as New York Heart Association functional status II or III were randomized to divide either a balneotherapy group or a control group. The patients in the balneotherapy group were immersed in a hot spring at 40°C for 10 min daily for 2 weeks; the control group patients took a shower daily. The left ventricular ejection fraction (EF) and cardiothoracic ratio (CTR) were evaluated and plasma brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels were measured. The clinical symptoms improved after 2 weeks of hot spring therapy. Although the heart rate did not change, clinical symptoms, CTR, EF, and BNP were significantly improved. Moreover, the inflammatory responses, including hsCRP, TNF-α and IL-6 decreased significantly after balneotherapy. The improvement of BNP correlates with the changes in inflammatory biomarkers. Repeated hyperthermia by bathing in a hot spring is therefore considered to improve the cardiac and inflammatory status in patients with CHF.

Low-level laser therapy improves the inflammatory profile of rats with heart failure.

Following heart failure (HF), immune activation leads to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Low-level laser therapy (LLLT) has been used as an anti-inflammatory treatment in several disease conditions. However, the effect of LLLT on the skeletal muscle of rats with HF remains unclear. The present report aimed to evaluate the influence of LLLT on the inflammatory profile of rats with HF. The left coronary artery was ligated to induce HF and a sham operation was performed in the control groups. Male Wistar rats (n=49) were assigned to one of six groups: placebo sham rats (P-Sham; n=8), LLLT at a dose of 3 J/cm(2) sham rats (3 J/cm(2)-Sham; n=8), LLLT at a dose of 21 J/cm(2) sham rats (21 J/cm(2)-Sham; n=8), placebo HF rats (P-HF; n=9), LLLT at a dose of 3 J/cm(2) HF rats (3 J/cm(2)-HF; n=8), and LLLT at a dose of 21 J/cm(2) HF rats (21 J/cm(2)-HF; n=8). Four weeks after myocardial infarction or sham surgery, rats were subjected to LLLT (InGaAlP 660 nm, spot size 0.035 cm(2), output power 20 mW, power density 0.571 W/cm(2), energy density 3 or 21 J/cm(2), exposure time 5.25 s and 36.75 s) on the right gastrocnemius for 10 consecutive days. LLLT reduced plasma IL-6 levels (61.3 %; P<0.01), TNF-α/IL-10 (61.0 %; P<0.01) and IL-6/IL-10 ratios (77.3 %; P<0.001) and increased IL-10 levels (103 %; P<0.05) in the 21 J/cm(2)-HF group. Moreover, LLLT reduced the TNF-α (20.1 % and 21.3 %; both P<0.05) and IL-6 levels (54.3 % and 37.8 %; P<0.01 and P<0.05, respectively) and the IL-6/IL-10 ratio (59.7 % and 42.2 %; P<0.001 and P<0.05, respectively) and increased IL-10 levels (81.0 % and 85.1 %; both P<0.05) and the IL-10/TNF-α ratio (171.5 % and 119.8 %; P<0.001 and P<0.05, respectively) in the gastrocnemius in the 3 J/cm(2)-HF and 21 J/cm(2)-HF groups. LLLT showed systemic and skeletal muscle anti-inflammatory effects in rats with HF.

Neuroimmune mechanisms of depression in heart failure.

Heart failure (HF) is a major and costly public health concern, and its prognosis is grim-with high hospitalization and mortality rates. It is well documented that HF patients experience disproportionately high rates of depression and that depressed HF patients have worse clinical outcomes than their non-depressed counterparts. The purpose of this chapter is to introduce the reader to the study of depression in HF, and how psychoneuroimmunologic principals have been applied to further elucidate the mechanisms (i.e., neurohormonal and cytokine activation) linking these co-morbid disorders.

Immunosuppression decreases inflammation and increases AAV6-hSERCA2a-mediated SERCA2a expression.

The calcium pump SERCA2a (sarcoplasmic reticulum calcium ATPase 2a), which plays a central role in cardiac contraction, shows decreased expression in heart failure (HF). Increasing SERCA2a expression in HF models improves cardiac function. We used direct cardiac delivery of adeno-associated virus encoding human SERCA2a (AAV6-hSERCA2a) in HF and normal canine models to study safety, efficacy, and the effects of immunosuppression. Tachycardic-paced dogs received left ventricle (LV) wall injection of AAV6-hSERCA2a or solvent. Pacing continued postinjection for 2 or 6 weeks, until euthanasia. Tissue/serum samples were analyzed for hSERCA2a expression (Western blot) and immune responses (histology and AAV6-neutralizing antibodies). Nonpaced dogs received AAV6-hSERCA2a and were analyzed at 12 weeks; a parallel cohort received AAV-hSERCA2a and immunosuppression. AAV-mediated cardiac expression of hSERCA2a peaked at 2 weeks and then declined (to ~50%; p<0.03, 6 vs. 2 weeks). LV end diastolic and end systolic diameters decreased in 6-week dogs treated with AAV6-hSERCA2a (p<0.05) whereas LV diameters increased in control dogs. Dogs receiving AAV6-hSERCA2a developed neutralizing antibodies (titer ≥1:120) and cardiac cellular infiltration. Immunosuppression dramatically reduced immune responses (reduced inflammation and neutralizing antibody titers <1:20), and maintained hSERCA2a expression. Thus cardiac injection of AAV6-hSERCA2a promotes local hSERCA2a expression and improves cardiac function. However, the hSERCA2a protein level is reduced by host immune responses. Immunosuppression alleviates immune responses and sustains transgene expression, and may be an important adjuvant for clinical gene therapy trials.

Spiritual activation in very elderly individuals assessed as heart rate variability and plasma IL/10/IL-6 ratios.

Proinflammatory cytokine responses might occur in elderly individuals with cardiovascular (CV) disease, cerebro-vascular (CVA) disease, and/or pulmonary disease (PD). Spiritual activation is an important coping mechanism, since psychiatric depression is an important risk factor for these individuals. Thirty-three very elderly individuals (87 ± 8 years) with previous CVD, CVA and/or PD participated in weekly 30 minute sermons by chaplains for over 20 months of chaplain liturgy (CL group). All underwent Holter ECG during the procedures and cardiac autonomic activities were assessed by maximum entropy analysis. Plasma IL-10 and IL-6 levels were compared with 26 age-matched (85 ± 10 years) individuals who did not participate in these activities (non-CL group). Both high frequency (HF) and pNN50 of heart rate variability (HRV) were higher in the CL group than in the non-CL group (HF, 190 ± 55 versus 92 ± 43 nu, P < 0.05; pNN50, 10.5 ± 16% versus 3.6 ± 3.8%, P < 0.05), whereas LF/HF was lower (1.4 ± 1.5 versus 2.2 ± 2.8, P < 0.05). Levels of IL-10/IL-6 were higher in the CL group (3.96 ± 5.0 versus 1.79 ± 1.6, P < 0.05). Hospitalization rates due to CVD and/or PD were lower in the CL group than in the non-CL group (4/33 versus 11/26, P < 0.05). We conclude that spiritual activation can modify proinflammatory cytokines and suppress CVD, CVA and/or PD via vagal modifications. Spiritual activation might be helpful for health in these very elderly individuals.

The effect of beta-blockers on the adaptive immune system in chronic heart failure.

It remains possible that the benefit from beta-blockers (BBs) in chronic heart failure (CHF) may not entirely be derived from a class-specific effect. Several experimental reports have alluded to the capability of immunomodulation by individual BBs. Given the increasingly recognized importance of the immune system in the pathogenesis of CHF, we studied the effects of BBs on the circulating immune system of these patients. Blood samples from CHF outpatients were prospectively analyzed using flow cytometry and gating software. Results were analyzed against comprehensive clinical details that were recorded during sample donation, including the type of BB administered. 273 blood samples were analyzed from 141 CHF patients, with an average ejection fraction of 31.9% and a mean age of 69.1 years. Patients taking carvedilol had a significantly lower expression of CD107a on cytotoxic T cells compared to bisoprolol (P= 0.001) and nebivolol (P= 0.008). They also had a significantly lower expression of HLA-DR on lymphocytes (P < 0.001 and P= 0.009 for bisoprolol and nebivolol, respectively). Cytotoxic T cells and lymphocytes expressing HLA-DR have been implicated in the pathogenesis of CHF. The fact that carvedilol, but not other commonly used beta-blockers, appears to modulate these important parameters, supports the concept that important differences exist between these agents, which may affect outcomes in CHF.

Marine polyunsaturated fatty acids in heart failure. Are the theoretical benefits matched by the clinical data?

Chronic heart failure (CHF) is a common condition, which despite major advances, is still characterized by high mortality (with sudden arrhythmic death a particular risk), poor quality of life due to exercise intolerance and frequent hospitalizations. Epidemiological studies suggest that populations with a high intake of marine polyunsaturated fatty acids (PUFAs or fish oils) have low levels of cardiovascular mortality. Animal and human studies of fish oil supplementation have demonstrated improved endothelial function and myocardial relaxation, reduced vascular tone and platelet aggregability, and a stabilization of myocyte excitability by prolongation of the refractory period. Marine PUFAs also have potentially important immune-modulating effects, reducing cytokine production and release, and altering prostaglandin metabolism. Data from patients following acute myocardial infarction have suggested that marine PUFA supplementation may reduce early mortality, mostly by reducing the risk of sudden arrhythmic death. Until recently, data in patients with chronic heart failure was lacking, but the recent publication of the GISSI-HF study, randomizing more than 7000 CHF patients to marine PUFA supplementation or placebo has clarified somewhat the role of these agents. The aim of this article is to review the theoretical benefits of marine PUFAs and to discuss the implications of the GISSI-HF study for the management of patients with CHF.

Evaluation of hawthorn extract on immunomodulatory biomarkers in a pressure overload model of heart failure.

BACKGROUND: Hawthorn extract (Crataegeus sp.) a botanical complementary and alternative medicine is often used to treat heart failure. The mechanism(s) by which hawthorn extract may treat heart failure is unknown but may include, theoretically, immunological effects. Therefore, the purpose of this study is to determine the effect of hawthorn extract on the immunomodulatory response in a pressure overload model of heart failure. MATERIAL/METHODS: A total of 62 male Sprague-Dawley rats were randomized to either aortic constriction + vehicle (AC; n=15), aortic constriction + hawthorn 1.3 mg/kg (HL, n=17), aortic constriction + hawthorn 13 mg/kg (HM, n=15), or aortic constriction + hawthorn 130 mg/kg (HH, n=15). Six months after surgical procedure animals were sacrificed and plasma samples obtained for the measurement of the following immunomodulatory markers: interleukin (IL) IL-1ss, IL-2, IL-6, IL-10; and leptin. RESULTS: The mortality rate following 6 months of aortic constriction was 40% in the AC group compared to 41%, 60%, and 53% for the HL, HM, and HH groups respectively (P>0.05 compared to AC). Aortic constriction produced a similar increase in the left ventricle/body weight ratio for all groups. Hawthorn extract had no effect on the immunomodulatory markers measured in this study, although there appeared to be a trend suggesting suppression of IL-2 plasma concentrations. CONCLUSIONS: In this animal model of heart failure, hawthorn extract failed to significantly affect the immunomodulatory response characterized after 6 months of pressure overload at a time when approximately 50% mortality was exhibited. Mechanisms other than immunological may better define hawthorn's effect in treating heart failure.

Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic heart failure.

Chronic heart failure is a complex catabolic state that carries a devastating prognosis. The transition from stable disease to cardiac cachexia is not well understood. Mechanisms that maintain the wasting process involve neurohormones and pro-inflammatory cytokines, which contribute to an imbalance in anabolic and catabolic pathways. A decrease in food intake alone rarely triggers the development of a wasting process, but dietary deficiencies in micronutrients and macronutrients contribute to the progression of the disease. Malabsorption from the gut as a result of bowel wall edema and decreased bowel perfusion also plays an important role. This article describes the complex interplay of hormonal systems in energy balance in patients with chronic heart failure as well as other factors such as malabsorption and dietary deficiencies that contribute to the wasting process. Finally, therapeutic approaches are discussed. These include dietary advice, ongoing studies, and future possibilities.

Functional electrical stimulation improves endothelial function and reduces peripheral immune responses in patients with chronic heart failure.

BACKGROUND: Previous studies have shown beneficial effects of functional electrical stimulation (FES) on muscle performance and exercise capacity of patients with chronic heart failure. This study evaluates the impact of FES on endothelial function and peripheral markers of immune activation in patients with moderate to severe heart failure. METHODS: Twenty-four patients with a left ventricular ejection fraction of less than 40% and New York Heart Association class II-III symptoms, undergoing optimized drug therapy, were randomly assigned (2 : 1) to a 6-week training programme of FES (n=16) or served as controls (n=8). Endothelial function was assessed by Doppler flow-mediated dilatation (FMD) of the brachial artery before and after the training programme. Peripheral pro-inflammatory/anti-inflammatory markers such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1 and IL-10 were also measured before and after training. RESULTS: A significant improvement on the 6-min walk test (7.5+/-3.3%), Minnesota Living Score (18.2+/-8.6%) and FMD (38.5+/-15.1%) was observed only in the FES-treated group. FES also causes a significant reduction of TNF-alpha (-11.5+/-8.9%), sICAM-1 (-13.1+/-9.8%), and sVCAM-1 (-10.6+/-6.6%), as well as a respective increase in the ratio IL-10/TNF-alpha (37.1+/-29.4%). In the FES group, the percentage improvement in the Minnesota Living Score was significantly correlated with respective changes in circulating TNF-alpha (r=0.624, P<0.01), sVCAM-1 (r=0.665, P<0.001) and the ratio IL-10/TNF-alpha (r=-0.641, P<0.01). CONCLUSION: FES is an exercise training programme that improves endothelial function in patients with chronic heart failure, and also has anti-inflammatory effects.

Metabolic and immunologic derangements in cardiac cachexia: where to from here?

The onset of cardiac cachexia is characterized by a defined severe weight loss in patients with advanced chronic heart failure and it predicts an increased mortality in these patients. Recent studies with potential therapeutics investigated the effects and efficiency of beta-blockers, ghrelin, or ghrelin-agonists in cachexia. These and other new studies, like the influence of heart transplantation on cardiac cachexia, give prospect into potential therapeutic options in the future. General aim of the treatment strategy is to prevent the onset and retard the progress of cachexia. This could be achieved by modifying the metabolic, neurohormonal and immune system abnormalities, e.g. with beta-blockers and angiotensin-converting enzyme inhibitors. However, these alterations interact in a complex pathophysiological process, which is supposed to end in a vicious circle and thereby the wasting process is further promoted. To interrupt this, an early start of therapy is important to decelerate the development of cardiac cachexia. Many further investigations are needed to find out more about the pathophysiological pathways, to confirm the previous results, and to evaluate new therapeutics.

[Effect of Astragalus injection on plasma levels of apoptosis-related factors in aged patients with chronic heart failure].

OBJECTIVE: To investigate the effect of Astragalus injection (AI) on plasma levels of apoptosis-related factors in aged patients with chronic heart failure (CHF). METHODS: Seventy-two CHF patients were randomly divided into the AI group (36 cases) treated with AI and the control group (36 cases) treated with conventional treatment. Plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assays (ELISA) with monoclonal anti-human antibodies. Besides, New York Heart Association (NYHA) grading was assessed according to improved symptoms and left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were assessed by echocardiogram after 4 weeks of treatment. RESULTS: After 4 weeks of treatment, NYHA grading was markedly improved in the two groups, but it was significantly better in AI group than that in the control group (P < 0.05). As compared with the control group, sFas, sFasL, TNF-alpha and IL-6 in the AI group were obviously lower, the difference between the two groups and between before and after treatment were significant (P < 0.05 or P < 0.01). Moreover, in AI group, LVESV and LVEDV decreased, LVEF increased, which was significantly different than that before treatment (P < 0.05), respectively. CONCLUSION: AI could lower plasma levels of apoptosis-related factors, and is one of the effective drugs in improving cardiac function in the aged patients with CHF.

[Effect of Shenqi Fuzheng injection (SFI) on immune function in patients with congestive heart failure].

OBJECTIVE: To study the effect of Shenqi Fuzheng injection on the humoral immunity (IgG IgM IgA), cellular immunity (T-lymphocyte subsets), Superoxide dismutase (SOD). Lpo and Plasma viscosity in the patients with congestive heart failure (CHF). METHODS: Sixty patients with CHF, whose heart function belonged to NYHA grade II-IV were randomly divide into two groups. The treaded group were treated with SFI 100 ml, and the control group were treated by nitroglycerine in jection 10 mg, the drug were administered respectively by adding in 5% glucose solution 500 ml for intravenous dripping, once a day, 20 days as one therapeutic course. Venous blood from cubital vein was collected before and after treatment to detect the IgG, IgM, IgA, T-lymphocyte subsets, SOD, LPO and Plasma viscosity. RESULTS: The clinical heart function markedly improved rate and total effective rate in the treated group was singificantly better than those in the control group respectively (P < 0.05). the left ventricular ejecting frection (LVEF) and end syctolic volume (ESV) were improved in both group (P < 0.05, P < 0.01), and the improvement in the treated group was superior to that in the control group (P < 0.05). In the treated group after treatment, the CD4, SOD level and CD4/DC8 ratio increased (P < 0.05), level of LPO, IgG and IgM lowered (P < 0.05) significantly, while those in the control group were not changed singificantly (P > 0.05). Plasma viscosity of treatment group also got better improved than before (P < 0.05), and there was a significantly difference between the two groups after treatment (P < 0.05). CONCLUSION: SFI Can improve the immune funtion of CHF patients, and can be taken as an importmant auxiliary treatment for CHF.