[A correlation study between body mass index and exercise capacity in patients with chronic systolic heart failure].

OBJECTIVE: To investigate the association between body mass index (BMI) and exercise capacity in patients with chronic systolic heart failure. METHODS: The elderly patients with chronic systolic heart failure were consecutively recruited from 2008 to 2011 in cardiovascular clinic of Zhejiang Hospital. All the participants underwent height and weight measurements and BMI was calculated with these two parameters. Cardiopulmonary exercise test were performed to achieve peak oxygen uptake (PVO(2)), oxygen uptake to body mass ratio (PKVO(2)), oxygen uptake to heart ratio (VO(2)/HR) and ventilation/carbon dioxide production (VO(2)/VCO(2)). RESULTS: A total of the 273 patients with chronic systolic heart failure included 6 underweight patients (BMI < 18.5 kg/m(2)), 113 normal weight patients (BMI 18.5 - < 24.0 kg/m(2)), 116 overweight patients (BMI 24.0 - < 28.0 kg/m(2)), and 38 obese patients (BMI ≥ 28 kg/m(2)). In both NYHA II and III/IV patients, unadjusted correlation analyses showed that BMI was positively related to PVO(2) and VO(2)/HR, and was inversely related to PKVO(2) and VE/VCO(2) (P < 0.05), respectively. Multiple stepwise regression analyses showed age, sex, BMI (P < 0.05) and left ventricular ejection fraction (LVEF) were independent determinants of PKVO(2), and age and BMI (P < 0.05) were independent determinants of VE/VCO(2). CONCLUSIONS: BMI is significantly associated with exercise capacity in patients with chronic systolic heart failure, and also independent determinant for the PKVO(2) and VE/VCO(2), respectively.

Structured lipid emulsion as nutritional therapy for the elderly patients with severe sepsis.

BACKGROUND: The nutritional support is one of the important therapeutic strategies for the elderly patients with severe sepsis, but there is controversial in choosing a parenteral nutrition formulation. This study was designed to compare the therapeutic effects of structured lipid emulsion, physically mixed medium, and long-chain fat emulsion in the treatment of severe sepsis in elderly patients. METHODS: A total number of 64 elder patients with severe sepsis were enrolled in the study. After a week of enteral nutritional support, the patients were randomly divided into research (structured lipid emulsion as parenteral alimentation) and control groups (physically mixed medium and long-chain fat emulsion as parenteral alimentation). The alterations of plasma albumin, lipid metabolism, and blood glucose level were recorded after parenteral alimentation and were compared between the two groups. RESULTS: The plasma levels of albumin, prealbumin, cholesterol, and triglyceride were decreased in all the patients after one week of enteral nutritional support treatment (t = 7.78, P = 0.000; t = 10.21, P = 0.000; t = 7.99, P = 0.000; and t = 10.99, P = 0.000). Further parenteral alimentation with different lipid emulsions had significant effects on the serum prealbumin and albumin (t = 3.316, P = 0.002; t = 3.200, P = 0.002), whilst had no effects on the blood glucose and triglyceride level (t = 7.78, P = 0.000; t = 4.228, P = 0.000). In addition, the two groups had a significantly different Apache II score, ventilator time, and hospital stay time (t = -2.213, P = 0.031; t = 2.317, P = 0.024; t = 2.514, P = 0.015). CONCLUSIONS: The structured lipid emulsion was safe as parenteral nutrition for elderly patients with severe sepsis. It was demonstrated to be superior to the physically mixed medium and long-chain fat emulsion with respect to the protein synthesis and prognosis.

Role of mitochondrial damage during cardiac apoptosis in septic rats.

BACKGROUND: Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats. METHODS: Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection. Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy. In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis. Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage. Oxidative stress was assessed by mitochondrial lipid and protein oxidation, and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity. RESULTS: Sepsis-induced inflammatory cell infiltration, myocardium degeneration and dropsy were time-dependent. Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge. Compared with sham-treated rats, the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours, 12 hours and 24 hours post-injection (P < 0.05). The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis, indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B. Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner. Both superoxide dismutase and glutathione peroxidase activities decreased, while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge. CONCLUSIONS: Septic challenge induced myocardial apoptosis and mitochondrial damage. Furthermore, mitochondrial damage via alteration of defenses against reactive oxygen species might play an important role in myocardial apoptosis during sepsis.

Combination of B-type natriuretic peptide and minute ventilation/carbon dioxide production slope improves risk stratification in patients with diastolic heart failure.

BACKGROUND: Recent studies demonstrated that the minute ventilation/carbon dioxide production (VE/VCO(2)) slope more powerfully predicted mortality, hospitalization, or both than peak oxygen consumption (VO(2)) in systolic heart failure. However, the prognostic values of these two parameters in diastolic heart failure remained unclear. METHODS: The patients with diastolic heart failure were recruited from April 2006 to May 2007, and underwent cardiopulmonary exercise testing. Plasma BNP concentration was measured using Triage BNP immunoassay method. RESULTS: Of the 224 patients enrolled, mean values for age and New York Heart Association (NYHA) class were 68.8 ± 9.0 years and 2.38 ± 0.53, respectively. During the mean follow-up of 30 months, 57 patients died (36 from cardiovascular death). Univariate Cox regression analysis showed that age, NYHA class, atrial fibrillation, diabetes mellitus, left ventricular diastolic dysfunction, peak VO(2), VE/VCO(2) slope, and plasma BNP were significantly associated with mortality. Multivariate analysis revealed that plasma BNP, VE/VCO(2) slope, and age remained independent predictors for cardiovascular and all-cause mortalities, with the strongest prognostic power of plasma BNP (χ(2) ≥ 31.4, P < 0.001). In addition to plasma BNP and clinical predictors, the VE/VCO(2) slope could provide independent and incremental prognostic value of cardiovascular (χ(2) = 60.6 vs 51.7; P = 0.009) and all-cause mortalities (χ(2) = 62.8 vs 54.2; P = 0.015) with increased χ(2) value of Cox regression model. CONCLUSION: In diastolic heart failure, plasma BNP is the strongest predictor of mortality, and VE/VCO(2) slope provides independent and additive prognostic information, which suggests that combination of plasma BNP and VE/VCO(2) slope can improve risk stratification.

Homocysteine-induced caspase-3 activation by endoplasmic reticulum stress in endothelial progenitor cells from patients with coronary heart disease and healthy donors.

Previous studies have suggested an association of hyperhomocysteinemia-induced vascular pathology with enhanced apoptotic potential of endothelial progenitor cells in patients with coronary heart disease. Our results indicate that 500 µmol/L homocysteine induced endothelial progenitor cell apoptosis and activation of caspase-3, both of which were abolished by 100 µmol/L and 200 µmol/L salubrinal, an agent that prevents endoplasmic reticulum stress-induced apoptosis. The addition of 500 µmol/L homocysteine caused a release of Ca(2+) from intracellular stores, and enhanced phosphor-eukaryotic initiation factor 2α phosphorylation at Ser51 and the expression of a glucose-regulated protein of 78 kDa and a C/EBP homologous protein independently of extracellular Ca(2+). These effects of homocysteine on endothelial progenitor cells were significantly greater in patients with coronary heart disease than in healthy donors. These findings suggest that homocysteine induces endoplasmic reticulum stress-mediated activation of caspase-3 in endothelial progenitor cells, an event that is enhanced in patients with coronary heart disease. Furthermore, enhanced endoplasmic reticulum stress-mediated activation of caspase-3 in endothelial progenitor cells might be involved in hyperhomocysteinemia-associated vascular pathology.

[An evaluation of stroke volume variation as a predictor of fluid responsiveness in mechanically ventilated elderly patients with severe sepsis].

OBJECTIVE: To evaluate stroke volume variation (SVV) as a predictor of fluid responsiveness in mechanically ventilated (MV) elderly patients with severe sepsis. METHODS: A prospective observation of 31 fluid challenges during fluid resuscitation for treatment of hemodynamic instability in 17 elderly MV patients with severe sepsis was conducted. SVV was measured by pulse indicator continuous cardiac output (PiCCO) system. Fluid responsiveness was defined as the changes in cardiac index (CI) increase after fluid loading (DeltaCI) > or =10%. The changes in hemodynamic parameters and lung water index were observed at the onset of and after fluid therapy. The correlation between DeltaCI and SVV or central venous pressure (CVP) were analyzed. RESULTS: SVV was decreased significantly after fluid loading [(6.6+/-2.1)% vs.(12.1+/-3.7)%, P<0.01], whereas CVP increased significantly [(12.5+/-3.6) mm Hg vs. (8.9+/-4.1) mm Hg, 1 mm Hg=0.133 kPa, P<0.01]. DeltaCI in response to fluid loading were positively correlated to initial values of SVV (r=0.447, P=0.012), but there was no relationship between CVP and DeltaCI (r=-0.082, P=0.674). The areas under the receiver operating characteristic curve (ROC curve) for SVV was 0.672 [95% confidence interval (95%CI) 0.463-0.885] and CVP was 0.336 (95%CI 0.133-0.539), respectively. A SVV value of 11.5% had the sensitivity of 71% and specificity of 67% for prediction of fluid responsiveness. CONCLUSION: Functional hemodynamic parameter SVV can predict fluid responsiveness in elderly MV patients with severe sepsis during fluid resuscitation, it may serve as a useful index for guiding fluid therapy in elderly patients with severe sepsis.

[Influence of glutamine and growth hormone intensified nutrition support on immunomodulation in critically ill elderly patients].

OBJECTIVE: To evaluate the impacts of glutamine (Gln) and recombinant human growth hormone (rhGH) intensified nutrition support on critically ill elderly patients. METHODS: Ninety critically ill aged patients were included in a prospective, randomized and controlled clinical study, and randomly divided into three groups: group A (standard nutrition support), group B (standard nutrition support+10% Gln 100 ml/d), group C (standard nutrition support+ Gln 100 ml/d+rhGH 10 U/d). Before treatment and then 7 and 14 days after treatment, blood samples were collected for analysis of serum proteins including albumin (ALB), pre-albumin (PAB), C-reactive protein (CRP), immunoglobulin G (IgG). Meanwhile, the variables including T-cell subsets, CD14 human leukocyte antigen (locus) DR (CD14 HLA-DR), and total lymphocytes were measured. The changes in acute physiology and chronic health evaluation II (APACHE II) and multiple organ dysfunction syndrome (MODS) scores, the durations of intensive care unit (ICU) stay and mechanical ventilation, and 28-day survival rate were recorded. RESULTS: Comparing with group A and B, the levels of serum ALB, PAB and IgG were significantly elevated in group C. The T-cell subsets, CD14 HLA-DR and the number of total lymphocytes were markedly higher in group C (P<0.01), and the APACHE II and MODS scores were decreased significantly in group C (P<0.05 or P<0.01). The levels of serum CRP were lowered significantly in group C (P<0.01). There were no significant differences in the durations of ICU stay, mechanical ventilation and 28-day survival rate among three groups (all P>0.05). CONCLUSION: Gln and rhGH intensified nutrition support can improve nutritional condition and immune function, downregulate the inflammatory response in the critically ill elderly patients.