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Biomedical subjects

M Rauchhaus

Publications and source records attributed to M Rauchhaus.

At least 19 recordsLinked to original sources
PubMed2001

High tumour necrosis factor-alpha levels are associated with exercise intolerance and neurohormonal activation in chronic heart failure patients.

Immune activation plays an important role in the progression of chronic heart failure (CHF). We sought to investigate whether different degrees of tumor necrosis factor-alpha (TNF-alpha) activation are associated with exercise intolerance, neurohormonal activation and alterations in muscle mass and function in patients with CHF without cardiac cachexia. Patients were divided into quartiles according to their TNF levels (first quartile: 0.98-4.90 pg/ml, second quartile: 5.00-6.60 pg/ml; third quartile 6.80-9.00 pg/ml; fourth quartile 9.80-32.00 pg/ml). Patients underwent cardiopulmonary exercise testing, quadriceps muscle strength test, quadriceps fatigue test, and assessment of thigh muscle and fat cross-sectional area (CSA) by computerized tomography scanning. Patients in the highest TNF quartile had the lowest peak oxygen consumption [13.1 (+/-4.1) ml/kg/min vs 18.1 (+/-5.3), 18.8 (+/-4.8) and 18.7 (+/-5.6) ml/kg/min, P<0.01] the greatest relation of ventilation and dioxide production (VE/VCO(2)) slope (P<0.05) and the most elevated catecholamine levels (P<0.05) compared to patients in the first three quartiles. Patients with the lowest TNF levels had preserved thigh muscle size and quadriceps strength. Strength/muscle CSA was similar in the four groups. Muscle strength during fatigue testing was significantly lower in the fourth quartile (P=0.01) compared with the other three groups. In CHF patients only the highest levels of TNF are associated with poor functional status and neurohormonal activation. This group of patients may represent the appropriate target population for TNF antagonism.

Aged↗
PubMed2001

Assessment of chemoreflex sensitivity in free breathing young subjects by correction for respiratory influence.

BACKGROUND: The assessment of autonomic function is an important tool for risk stratification in critically ill patients. Peripheral cardiac chemoreflex sensitivity has been considered a marker for increased risk of sudden cardiac death. In normals, the evaluation of peripheral cardiac chemoreflex sensitivity is performed under controlled breathing conditions during inhalation of hypoxic gas. Since this is poorly tolerated by patients, they are commonly studied under hyperoxic conditions, which are not physiological. METHODS: We studied 20 healthy volunteers who underwent free and controlled breathing of a hypoxic gas mixture (10% O2 in N2) over 5 min. Values of peripheral cardiac chemoreflex sensitivity, corrected for respiratory influence, were compared with the results obtained experimentally under controlled breathing conditions in the same subjects. RESULTS: We found a substantial difference between values obtained during free and controlled breathing (3.64 +/- 0.81 vs. 1.53 +/- 0.32 ms/mmHg, respectively; P < 0.05). After application of a respiratory correction, described and validated in this article, no significant difference was seen for these values (0.89 +/-0.91 vs. 1.53 +/- 0.32 ms/mmHg, P = 0.46). CONCLUSIONS: This approach allows the evaluation of peripheral cardiac chemoreflex sensitivity in free breathing subjects. This correction could improve the assessment of cardiac chemoreflex sensitivity in patients with cardiorespiratory disorders, who find it difficult to control their breathing according to an experimental protocol.

Adult↗
PubMed2001

Uric acid in cachectic and noncachectic patients with chronic heart failure: relationship to leg vascular resistance.

BACKGROUND: Chronic heart failure (CHF) is a hyperuricemic state, and capillary endothelium is the predominant site of xanthine oxidase in the vasculature. Upregulated xanthine oxidase activity (through production of toxic free radicals) may contribute to impaired regulation of vascular tone in CHF. We aimed to study the relationship between serum uric acid levels and leg vascular resistance in patients with CHF with and without cachexia and in healthy control subjects. METHODS: In 23 cachectic and 44 noncachectic patients with CHF (age, 62 +/- 1 years, mean +/- SEM) and 10 healthy control subjects (age, 68 +/- 1 years), we assessed leg resting and postischemic peak vascular resistance (calculated from mean blood pressure and leg blood flow by venous occlusion plethysmography). RESULTS: Cachectic patients, compared with noncachectic patients and control subjects, had the highest uric acid levels (612 +/- 36 vs 459 +/- 18 and 346 +/- 21 micromol/L, respectively, both P <.0001) and the lowest peak leg blood flow and vascular reactivity (reduction of leg vascular resistance from resting to postischemic conditions: 83% vs 88% and 90%, both P <.005). In all patients, postischemic vascular resistance correlated significantly and independently of age with uric acid (r = 0.61), creatinine (r = 0.47, both P <.0001), peak VO2 (r = 0.34), and New York Heart Association class (r = 0.33, both P <.01). This correlation was not present in healthy control subjects (r = -0.04, P =.9). In multivariate and stepwise regression analyses, serum uric acid emerged as the strongest predictor of peak leg vascular resistance (standardized coefficient = 0.61, P <.0001) independent of age, peak VO2, creatinine, New York Heart Association class, and diuretic dose. CONCLUSIONS: Hyperuricemia and postischemic leg vascular resistance are highest in cachectic patients with CHF, and both are directly related independent of diuretic dose and kidney function. The xanthine oxidase metabolic pathway may contribute to impaired vasodilator capacity in CHF.

Adult↗
PubMed2001

Leptin, insulin sensitivity and growth hormone binding protein in chronic heart failure with and without cardiac cachexia.

OBJECTIVE: Regulation of growth hormone (GH) receptor expression and hence tissue GH sensitivity may be important for the conflicting results found in treatment studies with recombinant growth hormone in chronic heart failure (CHF). Growth hormone-binding protein (GHBP) corresponds to the extracellular domain of the GH receptor and is closely related to measures of body composition and, specifically, to size of visceral fat tissue. Leptin, the adipocyte specific (ob) gene product, has been proposed as the signal linking adipose tissue and GHBP/GH-receptor expression. CHF has recently been shown to be a hyperleptinaemic and insulin-resistant state regardless of aetiology. This study aimed to examine the influence of leptin on GHBP in CHF patients with and without cardiac cachexia compared with healthy control subjects. METHODS: We studied 47 male patients with CHF (mean age 61+/-2 years, New York Heart Association (NYHA)-class 2.7+/-0.1, left ventricular ejection fraction (LVEF) 28+/-2%, peak oxygen consumption 16.8+/-0.9 ml/kg/min) and 21 male healthy controls of similar age. Of the CHF patients, 19 were cachectic (cCHF; non-oedematous weight loss >7.5% over at least 6 months) and 28 non-cachectic (ncCHF; similar for age and LVEF). Insulin sensitivity was assessed by an intravenous glucose tolerance test using the minimal model approach. RESULTS: Compared with healthy controls, patients had elevated levels of leptin (7.6+/-0.7 vs 4.8+/-0.7 ng/ml, P<0.05), insulin (76.2+/-8.9 vs 41.4+/-6.0 pmol/l, P<0.01), and reduced insulin sensitivity (2.43+/-0.2 vs 3.48+/-0.3 min(-1).microU.ml(-1).10(4), P<0.005) but similar GHBP levels (901+/-73 vs 903+/-95 pmol/l). Leptin levels were increased in ncCHF (9.11+/-1.0 ng/ml, P=0.001) but were not different from normal in cCHF (5.32+/-0.7 ng/ml, P>0.5). After correction for total body fat mass, both ncCHF and cCHF were hyperleptinaemic (41.8+/-3.8 and 37.9+/-0.38 vs 24.4+/-2.1 ng/ml/100 g, ANOVA P=0.001). In both patients and controls there was a direct correlation between leptin levels and GHBP (r=0.70 and r=0.71 respectively, both P<0.0001). This relationship was stronger than between GHBP and several parameters of body composition (body mass index (BMI), total and regional body fat mass or % body fat) and held true when sub-groups were tested individually (ncCHF r=0.62, P<0.001; cCHF r=0.79, P<0.0001). In multivariate regression analysis in all CHF patients, serum leptin levels emerged as the strongest predictor of GHBP, independent of age, BMI, total and regional fat mass or % body fat, fasting insulin level and insulin sensitivity. CONCLUSION: Fat mass corrected leptin levels are elevated in CHF patients with and without cachexia. Reduced total fat mass may account for lower leptin levels in cachectic CHF patients compared with non cachectic patients. Leptin strongly predicts GHBP levels in CHF regardless of its hyperleptinaemic state or severely altered body composition as in cardiac cachexia. Leptin could be the signalling link between adipose tissue and GHBP/GH receptor expression in CHF.

Adipose Tissue↗
PubMed2000

Plasma cytokine parameters and mortality in patients with chronic heart failure.

BACKGROUND: Inflammatory immune activation is an important feature in chronic heart failure (CHF). Little is known about the prognostic importance of tumor necrosis factor-alpha (TNF-alpha), soluble TNF-receptor 1 and 2 (sTNF-R1/sTNF-R2), interleukin-6 (IL-6), and soluble CD14 receptors (sCD14) in CHF patients. METHODS AND RESULTS: In 152 CHF patients (age 61+/-1 years, New York Heart Association [NYHA] class 2.6+/-0.1, peak VO(2) 17.3+/-0.6 mL. kg(-1). min(-1), mean+/-SEM) plasma concentrations of immune variables were prospectively assessed. During a mean follow-up of 34 months (>12 months in all patients), 62 patients (41%) died. Cumulative mortality was 28% at 24 months. In univariate analyses, increased total and trimeric TNF-alpha, sTNF-R1, and sTNF-R2 (all P</=0.0001), sCD14 (P=0.0007), and IL-6 (P=0.005) predicted 24-month mortality. With multivariate analysis and receiver operating characteristics, sTNF-R1 emerged among all cytokine parameters as the strongest and most accurate prognosticator in this CHF population, regardless of follow-up duration and independently of NYHA class, peak VO(2), VE/VCO(2) slope, left ventricular ejection fraction, and wasting (P<0.001). The receiver operating characteristic area under the curve for sTNF-R1 was greater than for sTNF-R2 at 6, 12, and 18 months (all P<0.05). CONCLUSIONS: sTNF-R1 was the strongest and most accurate prognosticator, independent of established markers of CHF severity. Assessment of sTNF-R1 may be useful in identifying patients who are at high risk of death and in monitoring patients undergoing anti-TNF-alpha treatment.

Adult↗
PubMed2000

The endotoxin-lipoprotein hypothesis.

The advent of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) has revolutionised the treatment of hypercholesterolaemia. Statin treatment, by lowering the atherogenic lipoprotein profile, reduces morbidity and mortality in patients with cardiovascular disease. Treatment with simvastatin causes a reduction of events of new-onset heart failure, but this may be attributable to properties other than its lipid-lowering effects. There is some evidence that lower serum cholesterol concentrations (as a surrogate for the totality of lipoproteins) relate to impaired survival in patients with chronic heart failure (CHF). Inflammation is a feature in patients with CHF and increased lipopolysaccharide may contribute substantially. We postulate that higher concentrations of total cholesterol are beneficial in these patients. This is potentially attributable to the property of lipoproteins to bind lipopolysaccharide, thereby preventing its detrimental effects. We hypothesise there is an optimum lipoprotein concentration below which lipid reduction would, on balance, be detrimental. We also propose that, in patients with CHF, a non-lipid-lowering statin (with ancillary properties such as immune modulatory and anti-inflammatory actions) could be as effective or even more beneficial than a lipid-lowering statin.

Animals↗
PubMed2000

The relationship of the erythrocyte sedimentation rate to inflammatory cytokines and survival in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors.

OBJECTIVES: The object of the study was to assess the relationship between erythrocyte sedimentation rate (ESR) and inflammatory cytokine production in chronic heart failure (CHF). Our findings lead us to re-evaluate the prognostic value of the ESR in assessing patients with CHF. BACKGROUND: The search for simple prognostic markers in CHF that can be assessed anywhere at low cost is important. Increases in ESR are related to the acute phase response in states of inflammation and infection. METHODS: Initially, we studied ESR in relation to plasma levels of inflammatory cytokines in 58 CHF patients. The findings prompted us to analyze the mortality predictive power of ESR compared with established risk factors in these patients and (retrospectively) in a second group of 101 clinically stable CHF patients who had ESR measured. RESULTS: In all 159 CHF patients (age 62+/-2 years, New York Heart Association [NYHA] class 2.7+/-0.1), ESR ranged from 1 to 96 mm/h (median 14 mm/h). The ESR was correlated with tumor necrosis factor (TNF)-alpha (r = 0.31, p<0.05), soluble TNF receptor-1 (r = 0.48, p<0.0005), soluble TNF receptor-2 (r = 0.39, p<0.005) and interleukin 6 (r = 0.45, p<0.005) levels. High ESR levels indicated a poor prognosis (p<0.0001), and this was independent of age, NYHA class, ejection fraction and peak oxygen consumption (p < 0.005). Patients with ESR above median (> or =15 mm/h) compared with patients with ESR <15 mm/h had an impaired survival (hazard ratio 2.62, 95% confidence interval 1.58-4.36, p<0.0001). CONCLUSIONS: Our study demonstrates that in CHF a high ESR is an unfavorable prognostic sign, independent of patients' symptomatology and ventricular function. These results are in diametrical contrast to previous results. This may reflect a change in the underlying pathophysiology due to today's treatment with angiotensin-converting enzyme inhibitors.

Adult↗
PubMed2000

Non-invasive assessment of vascular function; paradoxical vascular response to intravenous glucose in coronary heart disease.

BACKGROUND: In healthy individuals, insulin administration causes an increase in forearm blood flow which is dependent on the effects of insulin on the vascular endothelium. Glucose, administered as an intravenous bolus, produces a transient hyperinsulinaemic response. We hypothesized that the insulin response to an intravenous glucose challenge during the intravenous glucose tolerance test might lead to increases in forearm blood flow in healthy individuals, and that such a response might be altered in patients with coronary heart disease. METHODS AND RESULTS: Healthy individuals (n=10, aged 41.6+/-3. 0 years, mean+/-SEM) and patients with angiographically proven coronary heart disease (n=13, aged 65.5+/-2.4 years) underwent an intravenous glucose tolerance test with simultaneous measurement of right forearm blood flow at 28 time points, using mercury-in-silastic venous occlusion plethysmography. In controls, forearm blood flow increased to a mean of 31.7% above baseline values at 7 min and remained above baseline up to 180 min after intravenous glucose. In contrast, patients with coronary heart disease exhibited an opposite response, with forearm blood flow decreasing to a mean of -16.2% below baseline values at 7 min and -25.8% at 180 min. Marked group differences emerged in net changes from baseline in forearm blood flow throughout the intravenous glucose tolerance test, expressed as incremental areas under the forearm blood flow profiles (controls: +351.3+/-121.7; coronary heart disease patients: -244.3+/-72.4 min ml(-1). 100 ml(-1), P=0. 001). CONCLUSIONS: We have demonstrated for the first time that in healthy individuals forearm blood flow increases after an intravenous bolus of glucose, and that paradoxically, this response is reduced below baseline forearm blood flow in patients with coronary heart disease. Further studies are needed to determine whether plethysmographic measurement of forearm blood flow after an intravenous bolus of glucose could provide a clinically useful non-invasive test for the diagnosis of occult coronary heart disease.

Adult↗
PubMed1999

Origin of oscillatory kinetics of respiratory gas exchange in chronic heart failure.

BACKGROUND: Respiratory gas exchange measurements in patients with chronic heart failure (CHF) at rest and during exercise commonly reveal prominent slow oscillations in ventilation (V(E)), measured oxygen uptake (VO(2)), and carbon dioxide production (VCO(2)), whose origin is not clear. Voluntary simulation of periodic breathing (PB) in normals has been reported to generate a different pattern of oscillations in gas exchange from that seen in spontaneous PB. This necessitates hypothesizing that PB is caused by a primary oscillation in tissue metabolism or in cardiac output. METHODS AND RESULTS: We developed an automated method by which normal controls could be guided to breathe according to a PB pattern. The resultant metabolic oscillations closely matched those seen in spontaneous PB and had several interesting properties. At low workloads (including rest), the oscillations in VO(2) were as prominent as those in V(E) in both spontaneous PB (alpha(VO2)/alpha(VE)=0.92+/-0.04) and voluntary PB (0.93+/-0.07). However, at increased workload, the oscillations in VO(2) because less prominent than those in V(E) in spontaneous PB (intermediate workload 0.63+/-0.05, high workload 0.57+/-0.04; P<0.001) and voluntary PB (intermediate 0.66+/-0.03, high 0.48+/-0.03; P<0.001). There was no difference in the relative size of metabolic oscillations between voluntary and spontaneous PB at matched workloads (P>0.05 at low, intermediate, and high workloads). Furthermore, VO(2) peaked before V(E) in both spontaneous and voluntary PB. This time delay varied from 6.4+/-0.4 s at low ventilation, to 11.3+/-0.9 s at high ventilation (P<0.0001). CONCLUSIONS: The magnitude and phase pattern of oscillations in gas exchange of spontaneous PB can be obtained by adequately matched voluntary PB. Therefore, the gas exchange features of PB are explicable by primary ventilatory oscillation.

Adult↗
PubMed1999

Endotoxin and immune activation in chronic heart failure: a prospective cohort study.

BACKGROUND: Immune activation in patients with chronic heart failure may be secondary to endotoxin (lipopolysaccharide) action. We investigated the hypothesis that altered gut permeability with bacterial translocation and endotoxaemia would be increased in patients with oedema secondary to congestive heart failure. METHODS: We compared 20 patients who had chronic heart failure with recent-onset peripheral oedema (mean age 64 years [SD 10], New York Heart Association [NYHA] class 3.3 [0.7]), 20 stable non-oedematous patients with chronic heart failure (mean age 63 years [19], NYHA class 2.6 [0.7]), and 14 healthy volunteers (mean age 55 years [16]). Biochemical markers of endotoxaemia, inflammation, and immune activation were measured. Ten patients were studied within 1 week of complete resolution of oedema. Five patients survived longer than 6 months and were restudied again after remaining free of oedema for more than 3 months. FINDINGS: Mean endotoxin concentrations were higher in oedematous patients with chronic heart failure than in stable patients with chronic heart failure (0.74 [SD 0.45] vs 0.37 EU/mL [0.23], p=0.0009) and controls (0.46 EU/mL [0.21], p=0.02). Oedematous patients had the highest concentrations of several cytokines. After short-term diuretic treatment, endotoxin concentrations decreased from 0.84 EU/mL [0.49] to 0.45 EU/mL [0.21], p<0.05) but cytokines remained raised. After freedom of oedema for more than 3 months after oedema resolved, endotoxin concentrations remained unchanged from the previous visit (0.49 EU/mL [0.06], p=0.45). INTERPRETATION: Raised concentrations of endotoxin and cytokines are found in patients with chronic heart failure during acute oedematous exacerbation. Intensified diuretic treatment can normalise endotoxin concentrations. Our preliminary findings suggest that endotoxin may trigger immune activation in patients with chronic heart failure during oedematous episodes.

Acute-Phase Proteins↗