Biomedical subjects

Sandra Erbs

Publications and source records attributed to Sandra Erbs.

27 records · Page 2Linked to original sources

PubMed2003

Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure.

OBJECTIVES: The aim of this study was to assess the effects of regular physical exercise on local inflammatory parameters in the skeletal muscle of patients with chronic heart failure (CHF). BACKGROUND: Inflammatory activation with increased serum cytokine levels and expression of inducible nitric oxide synthase (iNOS) in the myocardium and peripheral skeletal muscles has been described in CHF. METHODS: Twenty male patients with stable CHF (left ventricular ejection fraction 25 +/- 2%; age 54 +/- 2 years) were randomized to a training group (n = 10) or a control group (n = 10). At baseline and after six months, serum samples and vastus lateralis muscle biopsies were obtained. Serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1-beta levels were measured by enzyme-linked immunosorbent assay, local cytokine, and iNOS expression by real-time polymerase chain reaction. RESULTS: Exercise training improved peak oxygen uptake by 29% in the training group (from 20.3 +/- 1.0 to 26.1 +/- 1.5 ml/kg. min; p < 0.001 vs. control group). While serum levels of TNF-alpha, IL-6, and IL-1-beta remained unaffected by training, local skeletal muscle TNF-alpha decreased from 1.9 +/- 0.4 to 1.2 +/- 0.3 relative U (p < 0.05 for change vs. control group), IL-6 from 71.3 +/- 16.5 to 41.3 +/- 8.8 relative U (p < 0.05 vs. begin), and IL-1-beta from 2.7 +/- 1.1 to 1.4 +/- 0.6 relative U (p = 0.02 vs. control group). Exercise training also reduced local iNOS expression by 52% (from 6.3 +/- 1.2 to 3.0 +/- 1.0 relative U; p = 0.007 vs. control group). CONCLUSIONS: Exercise training significantly reduced the local expression of TNF-alpha, IL-1-beta, IL-6, and iNOS in the skeletal muscle of CHF patients. These local anti-inflammatory effects of exercise may attenuate the catabolic wasting process associated with the progression of CHF.

Biopsy↗

PubMed2003

Promoter but not exon 7 polymorphism of endothelial nitric oxide synthase affects training-induced correction of endothelial dysfunction.

UNLABELLED: Background- Polymorphisms in the promoter (T-786C) and exon 7 (G894T) of the endothelial nitric oxide synthase (eNOS) gene were shown to be associated with reduced vascular NO production or increased proteolytic cleavage of eNOS. Therefore, we aimed to determine the effects of these polymorphisms on endothelial function and endothelial response to physical exercise in patients with coronary artery disease (CAD). METHODS AND RESULTS: Sixty-seven patients were randomized to either a training or a control group. At the beginning and after 4 weeks, acetylcholine-induced changes in average peak velocity (APV) of a coronary or mammary artery were invasively assessed by Doppler velocimetry. Polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. At the beginning, in subjects with the wild-type (WT) variant, APV increased by 88+/-7% in response to acetylcholine. This response was significantly blunted in patients who were positive for the promoter (44+/-7%) or the exon 7 (62+/-9%) polymorphism. Four weeks of exercise training resulted in augmentation of an endothelium-dependent increase in APV by +36+/-12% in promoter polymorphism-positive patients but by +81+/-18% and +91+/-15% in WT variant- and exon 7 polymorphism-positive subjects, respectively. CONCLUSIONS: These results suggest that the presence of either one of the polymorphisms attenuates endothelium-dependent vasodilatation in CAD patients. Only the promoter polymorphism might have an adverse effect on training-induced improvement in endothelial function.

Aged↗

PubMed2003

Muscular levels of proinflammatory cytokines correlate with a reduced expression of insulinlike growth factor-I in chronic heart failure.

OBJECTIVE: Chronic heart failure (CHF) is associated with metabolic abnormalities leading to a catabolic syndrome in advanced stages of the disease. To assess the role of proinflammatory cytokines for the local expression of insulin-like growth factor-I (IGF-I) in this process, muscular and systemic levels of interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNFalpha) and IGF-I were analyzed in an animal model of CHF. METHODS: Ligation of the left coronary artery or sham operation was performed in adult Wistar Kyoto rats. After 12 weeks, all animals were assessed by echocardiography and cardiac catheterization. Serum levels of IGF-I, IL-1beta, TNFalpha and IL-6 were determined by ELISA. In the quadriceps muscle, the expression of IGF-I, IGF-I receptor, IL-1beta and TNFalpha were assessed by RT-PCR and quantitative immunohistochemistry. Alterations in muscle fiber morphology were analyzed microscopically. RESULTS: The local expression of IGF-I decreased significantly in animals with CHF (0.47 +/- 0.07 versus 0.77 +/- 0.09; p < 0.01). This reduction correlated with a decreased muscle fiber cross-sectional area (r = 0.62; p < 0.01) and inversely with the local expression of IL-1beta (r = -0.49; p < 0.05). IGF-I serum levels showed no significant differences between the two groups. CONCLUSIONS: In CHF, the local IGF-I expression is reduced in the presence of normal serum levels of IGF-I. Both elevated proinflammatory cytokines and reduced local IGF-I expression contribute to a catabolic metabolism that may finally result in skeletal muscle atrophy and cardiac cachexia.

Animals↗

PubMed2003

Improvement of peripheral endothelial dysfunction by acute vitamin C application: different effects in patients with coronary artery disease, ischemic, and dilated cardiomyopathy.

BACKGROUND: Endothelial dysfunction has been described in patients with coronary artery disease (CAD) or chronic heart failure (CHF). Vitamin C administration leads to an improvement of endothelial function by reducing elevated levels of reactive oxygen species. It remains unclear, however, whether the degree of endothelial dysfunction caused by oxidative stress differs between CAD and CHF because of ischemic (ICM) or dilated cardiomyopathy (DCM). METHODS: In patients with CAD (n = 9; left ventricular ejection fraction [LVEF], 64% +/- 3%), ICM (n = 9; LVEF, 25% +/- 4%), DCM (n = 9; LVEF, 25% +/- 3%), and healthy subjects (HS; n = 5; LVEF, 66% +/- 5%) a change in internal radial artery diameter in response to acetylcholine (Ach; 15 and 30 microg/min) was measured with high-resolution ultrasound scanning during a co-infusion of normal saline or vitamin C (25 mg/min). RESULTS: Ach-mediated vasodilation was blunted in patients with CHF (DCM, 90 +/- 20 microm; ICM, 86 +/- 20 microm) and patients with CAD (336 +/- 20 microm) as compared with HS (496 +/- 43 microm; P <.05 vs patients with DCM, ICM, CAD). Vitamin C co-infusion increased Ach-mediated vasodilation by 180 +/- 35 microm (to 270 +/- 30 microm) in DCM (P <.05 vs CAD, HS) and by 294 +/- 40 microm (to 380 +/- 20 microm) in ICM (P <.05 vs DCM, CAD, HS). In patients with CAD, vitamin C increased Ach-mediated vasodilation by 146 +/- 35 microm to normal values, whereas vascular diameter remained unchanged in HS (14 +/- 20 microm; P = not significant). CONCLUSIONS: Acute vitamin C administration restored peripheral endothelial function in patients with CAD to normal values, whereas endothelial function remained attenuated in CHF, in particular in patients with DCM. These results suggest that in patients with CHF, factors other than oxidative stress (eg, cytokines) contribute to the pathologic endothelial function.

Acetylcholine↗

PubMed2003

Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure.

Patients with chronic heart failure (CHF) have metabolic abnormalities, leading to a catabolic syndrome, with progressive loss of skeletal muscle in advanced stages of the disease. Leptin, the product of an obesity gene, has been associated with energy expenditure and weight regulation. The aim of this study was to assess serum levels of leptin and its soluble receptor in relation to exercise intolerance and neurohumoral activation in patients with CHF. We investigated 53 patients with CHF left ventricular ejection fraction (LVEF) 25+/-1%, age 56.6+/-1.3 years, Maximal oxygen uptake (VO(2) max) 16.3+/-0.6 ml/min.kg) sub-classified according to peak oxygen consumption of > or 14 ml/min.kg and controls). Elevated levels of leptin correlated with an increased serum concentration of TNFalpha (r=0.749, P<0.01) in this subgroup of patients with CHF. We conclude that patients with advanced CHF show elevated serum levels of leptin and its soluble receptor. This finding indicates that leptin may participate in the catabolic state leading to the development of cardiac cachexia in the course of CHF.

Aged↗

PubMed2003

Home-based versus hospital-based exercise programs in patients with coronary artery disease: effects on coronary vasomotion.

BACKGROUND: In a randomized study, we recently documented that a vigorous, hospital-based exercise training (ET) program improves coronary endothelial function in coronary artery disease. The aim of this consecutive study was to assess whether a home-based exercise program with reduced average training duration can sustain previously achieved effects on coronary endothelial function. METHODS: Nineteen patients with coronary endothelial dysfunction documented by acetylcholine-induced vasoconstriction were randomly assigned to a training group (n = 10) or a control group (n = 9). After 4 weeks of inhospital training (60 min of bicycle ergometry per day), all training patients were enrolled in a 5-month home-based program of 20 minutes' ergometry training per day and 1 group training session per week. At baseline, after 4 weeks and 6 months, endothelium-mediated vasodilation was assessed by quantitative coronary angiography after intracoronary infusions of acetylcholine. Average peak velocity (APV) was measured with a Doppler wire. Coronary blood flow (CBF) was calculated by multiplying vascular cross-sectional area and APV. RESULTS: CBF increased in response to 7.2 microg/min acetylcholine, from 27% +/- 11% at the beginning of the study to 110% +/- 24% after 4 weeks (P <.01 vs control group). After 6 months, the increase in CBF was lower versus inhospital training (67% +/- 18%, P <.05 vs 4 weeks). Changes in APV between 1 and 6 months correlated with daily training durations (r = 0.65, P =.03). CONCLUSIONS: Home-based ET sustained part of the effects of hospital-based ET on endothelium-dependent vasodilation in coronary artery disease. However, acetylcholine-induced increases in CBF were lower after home-based ET, suggesting a relation between daily training duration and improvement of coronary vasomotion.

Aged↗

PubMed2003

Exercise training in patients with severe chronic heart failure: impact on left ventricular performance and cardiac size. A retrospective analysis of the Leipzig Heart Failure Training Trial.

BACKGROUND: Exercise training (ET) has been shown to improve functional work capacity in patients with stable chronic heart failure (CHF) having moderate symptoms (NYHA class II). This analysis was conducted, to evaluate the effects of ET on left ventricular function and haemodynamics in patients with advanced CHF (NYHA class III) fulfilling the inclusion criteria of the COPERNICUS trial. METHODS: Seventy-three patients with moderate and advanced CHF were prospectively randomised to a training (n=36), or to a control group (n=37). At baseline and after six months, patients underwent echocardiography and symptom-limited ergospirometry with measurement of central haemodynamics by thermodilution. RESULTS: Nine out of 37 patients in the control group (C) and 10 out of 36 patients in the training group (T) had symptoms of advanced CHF. Exercise training over a period of six months resulted in an improvement of functional status on average by one NYHA class in patients with advanced CHF. Moreover, oxygen uptake at the ventilatory threshold increased by 49% (from 7.7+/-1.0 to 11.4+/-0.4 mL/min/kg, P<0.01 versus baseline) and at peak exercise by 32% (from 16.3+/-1.6 to 21.5+/-1.2 mL/min/kg, P<0.01 versus baseline) in training patients. The small, but significant reduction in left ventricular end-diastolic diameter by 7% (from 70+/-2 to 66+/-2 mm; P<0.05 versus baseline) was accompanied by an augmentation in stroke volume at rest by 32% (from 45+/-3 to 60+/-6 mL, P<0.05 versus baseline) and at peak exercise by 27% (63+/-9 to 81+/-9 mL, P<0.05 versus baseline) as a result of ET in patients with advanced CHF. CONCLUSIONS: In patients with advanced CHF (NYHA class III), long-term exercise training is associated with an enhanced physical work capacity, an improvement in stroke volume and a reduction in cardiomegaly.

Cardiomegaly↗

PubMedDate not supplied

Exercise and the coronary circulation-alterations and adaptations in coronary artery disease.

Coronary vasorelaxation depends on nitric oxide (NO) bioavailability, which is a function of endothelial nitric oxide synthase-derived NO production and NO inactivation by reactive oxygen species. This fine-tuned balance is disrupted in coronary artery disease (CAD). The impairment of NO production in conjunction with excessive oxidative stress promotes the loss of endothelial cells by apoptosis, leads to a further aggravation of endothelial dysfunction and triggers myocardial ischemia in CAD. In healthy individuals, increased release of NO from the vasculature in response to exercise training results from changes in endothelial nitric oxide synthase expression, phosphorylation, and conformation. However, exercise training has assumed a role in cardiac rehabilitation of patients with CAD, as well, because it reduces mortality and increases myocardial perfusion. This has been largely attributed to exercise training-mediated correction of coronary endothelial dysfunction in CAD. Indeed, regular physical activity restores the balance between NO production and NO inactivation by reactive oxygen species in CAD, thereby enhancing the vasodilatory capacity in different vascular beds. Because endothelial dysfunction has been identified as a predictor of cardiovascular events, the partial reversal of endothelial dysfunction secondary to exercise training might be the most likely mechanism responsible for the exercise training-induced reduction in cardiovascular morbidity and mortality in patients with CAD.

Coronary Artery Disease↗

PubMedDate not supplied

Differential gene expression in skeletal muscle after induction of heart failure: impact of cytokines on protein phosphatase 2A expression.

Different intrinsic alterations of skeletal muscle metabolism and gene expression have been described in chronic heart failure (CHF). As proposed skeletal muscle alterations in CHF may contribute to exercise intolerance and early muscular fatigue. However the exact molecular changes occurring in the skeletal muscle are still unclear. The aim of this study was to characterize the pattern of differential gene expression in an animal model of CHF and to study the regulation of one selected gene. Rats were subjected to LAD ligation or sham operation. mRNA was isolated from musculus quadriceps of both groups and differential gene expression was determined by subtractive hybridization. Quantitative RT-PCR and cell culture experiments were performed to further characterize the changed expression of protein phosphatase 2A (PP2A) in human skeletal muscle biopsies as well as the cytokine dependent regulation of PP2A expression. Out of 800 picked clones differential expression of 24 distinct genes could be identified by sequencing and reverse Northern blotting. PP2A expression demonstrated a significant upregulation in skeletal muscle biopsies from patients with CHF as compared to healthy controls (9.7 +/- 1.9 vs. 4.2 +/- 0.7 arbitrary units; p<0.05). Incubation of rat skeletal muscle myoblasts with a combination of TNF-alpha, IL-1beta, and gamma-IFN caused a 3-fold upregulation of PP2A expression vs. untreated cells. These results suggest that CHF is accompanied by changes in expression of genes involved in energy metabolism, contractility, and apoptosis in the skeletal muscle. The upregulation of PP2A, an important regulator in intracellular signaling and apoptosis, may be due to an increase of inflammatory cytokines.

Animals↗