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Biomedical subjects

S Gielen

Publications and source records attributed to S Gielen.

31 records · Page 2Linked to original sources
PubMed2000

Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: A randomized trial.

CONTEXT: Exercise training in patients with chronic heart failure improves work capacity by enhancing endothelial function and skeletal muscle aerobic metabolism, but effects on central hemodynamic function are not well established. OBJECTIVE: To evaluate the effects of exercise training on left ventricular (LV) function and hemodynamic response to exercise in patients with stable chronic heart failure. DESIGN: Prospective randomized trial conducted in 1994-1999. SETTING: University department of cardiology/outpatient clinic in Germany. PATIENTS: Consecutive sample of 73 men aged 70 years or younger with chronic heart failure (with LV ejection fraction of approximately 0.27). INTERVENTION: Patients were randomly assigned to 2 weeks of in-hospital ergometer exercise for 10 minutes 4 to 6 times per day, followed by 6 months of home-based ergometer exercise training for 20 minutes per day at 70% of peak oxygen uptake (n=36) or to no intervention (control group; n=37). MAIN OUTCOME MEASURES: Ergospirometry with measurement of central hemodynamics by thermodilution at rest and during exercise; echocardiographic determination of LV diameters and volumes, at baseline and 6-month follow-up, for the exercise training vs control groups. RESULTS: After 6 months, patients in the exercise training group had statistically significant improvements compared with controls in New York Heart Association functional class, maximal ventilation, exercise time, and exercise capacity as well as decreased resting heart rate and increased stroke volume at rest. In the exercise training group, an increase from baseline to 6-month follow-up was observed in mean (SD) resting LV ejection fraction (0.30 [0.08] vs 0.35 [0.09]; P=.003). Mean (SD) total peripheral resistance (TPR) during peak exercise was reduced by 157 (306) dyne/s/cm(-5) in the exercise training group vs an increase of 43 (148) dyne/s/cm(-5) in the control group (P=.003), with a concomitant increase in mean (SD) stroke volume of 14 (22) mL vs 1 (19) mL in the control group (P=.03). There was a small but significant reduction in mean (SD) LV end diastolic diameter of 4 (6) mm vs an increase of 1 (4) mm in the control group (P<.001). Changes from baseline in resting TPR for both groups were correlated with changes in stroke volume (r=-0.76; P<.001) and in LV end diastolic diameter (r=0.45; P<.001). CONCLUSIONS: In patients with stable chronic heart failure, exercise training is associated with reduction of peripheral resistance and results in small but significant improvements in stroke volume and reduction in cardiomegaly. JAMA. 2000.

Aged↗
PubMed2000

Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation.

OBJECTIVES: The aim of this study was to analyze whether L-arginine (L-arg.) has comparable or additive effects to physical exercise regarding endothelium-dependent vasodilation in patients with chronic heart failure (CHF). BACKGROUND: Endothelial dysfunction in patients with CHF can be corrected by both dietary supplementation with L-arg. and regular physical exercise. METHODS: Forty patients with severe CHF (left ventricular ejection fraction 19 +/- 9%) were randomized to an L-arg. group (8 g/day), a training group (T) with daily handgrip training, L-arg. and T (L-arg. + T) or an inactive control group (C). The mean internal radial artery diameter was determined at the beginning and after four weeks in response to brachial arterial administration of acetylcholine (ACh) (7.5, 15, 30 microg/min) and nitroglycerin (0.2 mg/min) with a transcutaneous high-resolution 10 MHz A-mode echo tracking system coupled with a Doppler device. The power of the study to detect clinically significant differences in endothelium-dependent vasodilation was 96.6%. RESULTS: At the beginning, the mean endothelium-dependent vasodilation in response to ACh, 30 microg/min was 2.54 +/- 0.09% (p = NS between groups). After four weeks, internal radial artery diameter increased by 8.8 +/- 0.9% after ACh 30 microg/min in L-arg. (p < 0.001 vs. C), by 8.6 +/- 0.9% in T (p < 0.001 vs. C) and by 12.0 +/- 0.3% in L-arg. +/- T (p < 0.005 vs. C, L-arg. and T). Endothelium-independent vasodilation as assessed by infusion of nitroglycerin was similar in all groups at the beginning and at the end of the study. CONCLUSIONS: Dietary supplementation of L-arg. as well as regular physical exercise improved agonist-mediated, endothelium-dependent vasodilation to a similar extent. Both interventions together seem to produce additive effects with respect to endothelium-dependent vasodilation.

Acetylcholine↗
PubMed2000

Effect of exercise on coronary endothelial function in patients with coronary artery disease.

BACKGROUND: Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results. Exercise training has been associated with improvement in myocardial perfusion even in patients who have progression of coronary atherosclerosis. We therefore conducted a prospective study of the effect of exercise training on endothelial function in patients with coronary artery disease. METHODS: We randomly assigned 19 patients with coronary endothelial dysfunction, indicated by abnormal acetylcholine-induced vasoconstriction, to an exercise-training group (10 patients) or a control group (9 patients). To reduce confounding, patients with coronary risk factors that could be influenced by exercise training (such as diabetes, hypertension, hypercholesterolemia, and smoking) were excluded. In an initial study and after four weeks, the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine (0.072, 0.72, and 7.2 microg per minute) were assessed. The mean peak flow velocity was measured by Doppler velocimetry, and the diameter of epicardial coronary vessels was measured by quantitative coronary angiography. RESULTS: In the initial study, the two groups had similar vasoconstrictive responses to acetylcholine. After four weeks of exercise training, coronary-artery constriction in response to acetylcholine at a dose of 7.2 microg per minute was reduced by 54 percent (from a mean [+/-SE] decrease in the luminal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19+/-0.07 mm at four weeks; P<0.05 for the comparison with the change in the control group). In the exercise-training group, the increases in mean peak flow velocity in response to 0.072, 0.72, and 7.2 microg of acetylcholine per minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the initial study. After four weeks of exercise, the increases in response to acetylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comparison with the control group). Coronary blood-flow reserve (the ratio of the mean peak flow velocity after adenosine infusion to the resting velocity) increased by 29 percent after four weeks of exercise (from 2.8+/-0.2 in the initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison with the control group). CONCLUSIONS: Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease.

Acetylcholine↗
PubMed1999

Physical training as an adjunct therapy in patients with congestive heart failure: patient selection, training protocols, results, and future directions.

Exercise intolerance in patients with chronic heart failure (CHF) shows no correlation to the degree of left ventricular dysfunction. This surprising finding has directed attention to peripheral changes in CHF: reduced endothelium-dependent vasodilation and altered skeletal muscle metabolism. Physical exercise training has evolved as an important therapeutic approach to influence these noncardiac causes of exercise intolerance. It has been shown to enhance the oxidative capacity of the working skeletal muscle, to attenuate ergoreflex activity, to correct endothelial dysfunction, and to improve ventilation. All exercise-induced adaptations converge to increase peak oxygen uptake by up to 2 mL/kg.min(-1). Uncertainty remains concerning optimal patient selection, training protocol, and long-term effects on cardiac function. For patients experiencing stable CHF while on optimal cardiac medication, a combination of in-hospital and home-based aerobic endurance training in combination with local muscle strength training seems most promising. Although exercise training offers no causal treatment of CHF, it has great potential as an adjunct therapy directed at improving exercise tolerance and expanding the physical limits of CHF patients.

Arrhythmias, Cardiac↗
PubMed1999

Exercise intolerance in patients with chronic heart failure and increased expression of inducible nitric oxide synthase in the skeletal muscle.

OBJECTIVES: This study was designed to analyze the effect of iNOS on mitochondrial creatine kinase (mi-CK) expression and exercise capacity in chronic heart failure (CHF). BACKGROUND: The molecular mechanisms underlying exercise intolerance in CHF are still unclear. Expression of inducible nitric oxide synthase (iNOS) and reduced phosphocreatine resynthesis have been described in skeletal muscle of patients with CHF. However, it is unknown whether these phenomena are causally related to each other and to exercise tolerance. METHODS: Thirty-eight patients with CHF and 8 healthy controls (C) underwent bicycle ergospirometry and biopsy of the vastus lateralis muscle. Expression of iNOS was quantified by immunohistochemistry and reverse-transcriptase polymerase chain reaction, mi-CK by Western-blot. Intracellular presence of NO was confirmed by immunohistochemical quantification of nitrotyrosine (NT). To corroborate clinical findings, L6 rat skeletal myoblasts were incubated with sodium nitroprusside (SNP). RESULTS: Expression of iNOS was significantly increased in CHF (4.0+/-2.8 vs. 0.8+/-0.7% iNOS positive tissue area, p < 0.001 vs. C) and inversely correlated to maximal oxygen uptake (r=-0.65, p < 0.001). Intracellular NO-accumulation was confirmed by increased NT levels (13.5+/-8.5 vs. 2.0+/-1.7% NT-positive tissue area, p < 0.001 vs. C). Mi-CK was decreased in CHF (0.84+/-0.36 vs. 1.57+/-0.60, p < 0.001 vs. C). The inverse correlation seen between iNOS and mi-CK expression in patients (r=-0.68, p < 0.001) was reproduced in incubation experiments with SNP. CONCLUSIONS: Increased expression of iNOS in skeletal muscle of patients with CHF was inversely correlated with mi-CK expression and exercise capacity. Cell experiments confirmed a causal relationship via NO. These findings extend our knowledge of the pathophysiology of exercise intolerance in CHF.

Aged↗
PubMed1999

Partial retraining: a new approach to input relevance determination.

In this article we introduce partial retraining, an algorithm to determine the relevance of the input variables of a trained neural network. We place this algorithm in the context of other approaches to relevance determination. Numerical experiments on both artificial and real-world problems show that partial retraining outperforms its competitors, which include methods based on constant substitution, analysis of weight magnitudes, and "optimal brain surgeon".

Algorithms↗
PubMed1999

Phenotype in retinol deficiency due to a hereditary defect in retinol binding protein synthesis.

PURPOSE: To describe the phenotype caused by a retinol deficiency in a family with compound heterozygous missense mutations (Ile41Asn and Gly75Asp) in the gene for serum retinol binding protein (RBP). METHODS: The two affected sisters, 17 (BR) and 13 (MR) years old, were examined clinically and with perimetry, color vision tests, dark adaptometry, rod- and cone-isolated electroretinograms (ERGs), multifocal ERGs, electrooculograms (EOGs), and laboratory tests. RESULTS: There were no complaints besides night vision problems and no history of systemic disease. Visual acuity was reduced to 20/40 (BR) and 20/25 (MR). Anterior segments were normal except for a discrete iris coloboma. Both patients showed a typical "fundus xerophthalmicus," featuring a progressed atrophy of the retinal pigment epithelium. Dark adaptation thresholds were elevated. In the scotopic ERG, only reduced mixed responses were recordable. The photopic ERG was reduced in BR and normal in MR; implicit times were highly (BR) to slightly (MR) elevated. There was no (BR) to little (MR) light reaction in the EOG. All-trans retinol levels were 0.19 microM and 0.18 microM (normal range, 0.7-1.5 microM) for BR and MR, respectively, and did not increase in a dose-response test. RBP was below detection threshold, and retinyl esters were normal. CONCLUSIONS: Both affected siblings had no detectable serum RBP, one sixth of normal retinol levels, and normal retinyl esters. The retinal pigment epithelium was severely affected, but besides acne there were no changes to other organs. This gives evidence for an alternative tissue source of vitamin A, presumably retinyl esters from chylomicron remnants. The normal retinol levels in the tear fluid explain the lack of xerophthalmia. However, considering the role of RBP in the tear fluid and, during development, in the yolk sac there is also evidence that there are organ-specific RBP forms not affected by the genetic defect.

Adolescent↗
PubMed1998

Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure.

BACKGROUND: The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure (CHF). Endothelial dysfunction is a key feature of CHF, contributing to increased peripheral vasoconstriction and impaired exercise capacity. Local handgrip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF. METHODS AND RESULTS: Twenty patients were prospectively randomized to a training group (n=10, left ventricular ejection fraction [LVEF] 24+/-4%) or a control group (n=10, LVEF 23+/-3%). At baseline and after 6 months, peak flow velocity was measured in the left femoral artery using a Doppler wire; vessel diameter was determined by quantitative angiography. Peripheral blood flow was calculated from average peak velocity (APV) and arterial cross-sectional area. After exercise training, nitroglycerin-induced endothelium-independent vasodilation remained unaltered (271% versus 281%, P=NS). Peripheral blood flow improved significantly in response to 90 microg/min acetylcholine by 203% (from 152+/-79 to 461+/-104 mL/min, P<0.05 versus control group) and the inhibiting effect of L-NMMA increased by 174% (from -46+/-25 to -126+/-19 mL/min, P<0.05 versus control group). Peak oxygen uptake increased by 26% (P<0.01 versus control group). The increase in peak oxygen uptake was correlated with the endothelium-dependent change in peripheral blood flow (r=0.64, P<0. 005). CONCLUSIONS: Regular physical exercise improves both basal endothelial nitric oxide (NO) formation and agonist-mediated endothelium-dependent vasodilation of the skeletal muscle vasculature in patients with CHF. The correction of endothelium dysfunction is associated with a significant increase in exercise capacity.

Blood Flow Velocity↗
PubMed1998

Complete coding sequence of inducible nitric oxide synthase from human heart and skeletal muscle of patients with chronic heart failure.

The presence of the inducible nitric oxide synthase (iNOS) has previously been reported in heart and skeletal muscle of patients with chronic heart failure, where it is thought to be involved in the pathogenesis of dilated cardiomyopathy or of exercise intolerance observed in patients with chronic heart failure. To identify the iNOS of these human tissues the cDNA sequence was determined using reverse transcription polymerase chain reaction (RT-PCR). The deduced amino acid sequence of human heart and skeletal muscle shows a 99% identity between each other. The amino acid sequence was distinct from the constitutively expressed nitric oxide synthases. A 98% identity at the protein level was detected to rat vascular smooth muscle iNOS, whereas the homology to human hepatocyte iNOS was only 79%. The cofactor binding sites in the reported iNOS from human heart and skeletal muscle are highly conserved. The iNOS sequence described in this report is the first one isolated directly from human tissue expressing iNOS in the circumstances of chronic heart failure.

Amino Acid Sequence↗
PubMed1995

CT data acquisition as a basis for modern diagnosis and therapy in maxillofacial surgery.

More than 20 years after its introduction computed tomography has become a routine method in the diagnostic work-up of traumatic and neoplastic disorders in maxillofacial surgery. Short acquisition times of 1 sec per image reduce motion artifacts and permit increased numbers of patient examinations. Different reconstruction algorithms allow specific evaluation of either osseous or soft tissue structures. By adjusting window center and window width the 2048 attenuation values can be transformed into the visible gray scale. Single sequential slices--as employed in routine diagnosis of tumor patients--still yield the highest image quality. Fast volume data acquisition associated with spiral scanning proves to be of special benefit in trauma patients. The resulting data set can be used for reconstruction of single slices, 2-dimensional (2D) reformated images in all planes and 3D surface rendering.

Artifacts↗