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L Kaijser

Publications and source records attributed to L Kaijser.

At least 19 recordsLinked to original sources

Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle.

mRNA expression of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and hypoxia-inducible factor (HIF) subunits HIF-1alpha and HIF-1beta in human skeletal muscle was studied during endurance exercise at different degrees of oxygen delivery. Muscle biopsies were taken before and after 45 min of one-legged knee-extension exercise performed under conditions of nonrestricted or restricted blood flow (approximately 15-20% lower) at the same absolute workload. Exercise increased VEGF mRNA expression by 178% and HIF-1beta by 340%, but not HIF-1alpha and FGF-2. No significant differences between the restricted and nonrestricted groups were observed. The exercise-induced increase in VEGF mRNA was correlated to the exercise changes in HIF-1alpha and HIF-1beta mRNA. The changes in VEGF, HIF-1alpha, and HIF-1beta mRNAs were correlated to the exercise-induced increase in femoral venous plasma lactate concentration. It is concluded that 1) VEGF but not FGF-2 gene expression is upregulated in human skeletal muscle by a single bout of dynamic exercise and that there is a graded response in VEGF mRNA expression related to the metabolic stress and 2) the increase in VEGF mRNA expression correlates to the changes in both HIF-1alpha and HIF-1beta mRNA.

Adult

Substrate availability limits human skeletal muscle oxidative ATP regeneration at the onset of ischemic exercise.

We have demonstrated previously that dichloroacetate can attenuate skeletal muscle fatigue by up to 35% in a canine model of peripheral ischemia (Timmons, J.A., S.M. Poucher, D. Constantin-Teodosiu, V. Worrall, I.A. Macdonald, and P.L. Greenhaff. 1996. J. Clin. Invest. 97:879-883). This was thought to be a consequence of dichloroacetate increasing acetyl group availability early during contraction. In this study we characterized the metabolic effects of dichloroacetate in a human model of peripheral muscle ischemia. On two separate occasions (control-saline or dichloroacetate infusion), nine subjects performed 8 min of single-leg knee extension exercise at an intensity aimed at achieving volitional exhaustion in approximately 8 min. During exercise each subject's lower limbs were exposed to 50 mmHg of positive pressure, which reduces blood flow by approximately 20%. Dichloroacetate increased resting muscle pyruvate dehydrogenase complex activation status by threefold and elevated acetylcarnitine concentration by fivefold. After 3 min of exercise, phosphocreatine degradation and lactate accumulation were both reduced by approximately 50% after dichloroacetate pretreatment, when compared with control conditions. However, after 8 min of exercise no differences existed between treatments. Therefore, it would appear that dichloroacetate can delay the accumulation of metabolites which lead to the development of skeletal muscle fatigue during ischemia but does not alter the metabolic profile when a maximal effort is approached.

Acetylcarnitine

The ability of non-invasive physiological tests to detect arterial occlusions in the lower extremity. An ROC study with particular regard to recruitment of patients for clinical trials.

In the prerandomization phase of a clinical trial it is essential to be able to exclude, in a non-invasive way, patients who cannot be randomized into the trial. The ability of routine non-invasive physiological examinations to detect arterial occlusion in the lower extremities was investigated in 182 patients with hypercholesterolaemia. Ankle blood pressure measurement, pulse oscillometry, digital pulse plethysmography and treadmill and cycle exercise tests were performed as part of the prerandomization phase of the Probucol Quantitative Regression Swedish Trial (PQRST). The PQRST was designed to compare the antiatherosclerotic effect of two different lipid-lowering regimens. Before randomization the patients also underwent aorto-femoral arteriography, which was used as 'gold standard'. The results were analysed with ROC methodology. Ankle blood pressure measurement (ABP) and inclination time (IT), measured with digital pulse plethysmography, without significant mutual difference, were the variables, best able to detect occlusions. For ABP, the AZ-values were 0.85, 0.82 and 0.94 in detection of right-sided, left-sided and bilateral occlusion, respectively. The corresponding figures for IT were AZ = 0.86, 0.91 and 0.93. If a bilateral occlusion was predicted in a patient with an ABP value of < = or 0.98, a specificity of 0.90 and a sensitivity of 0.87 were obtained, using arteriography as reference method. For IT, with a critical value of 320 ms, sensitivity and specificity were 0.83 and 0.90, respectively.

Adult

Peak skeletal muscle perfusion is maintained in patients with chronic heart failure when only a small muscle mass is exercised.

OBJECTIVES: The issue to be resolved was whether peripheral leg blood flow in patients with chronic heart failure (CHF) is reduced by low local flow capacity or as a function of the amount of muscle mass activated during exercise. METHODS AND RESULTS: In ten CHF patients (ejection fraction 26 (9)%), and 12 healthy controls central and peripheral circulatory responses were assessed during dynamic one- and two-legged knee extensor work. The patients reached a peak perfusion of 234 (16) ml 100 g-1 min-1 in the one-legged mode, which was similar to the controls (244 (11) ml 100 g-1 min-1). At peak two-legged work muscle perfusion was reduced in the patients by 24% (P < 0.05). In contrast the controls maintained their peak muscle perfusion. The mass of the quadriceps femoris muscle and peak leg blood flow correlated closely for both groups at peak one-legged work (r = 0.85, P < 0.001). Peak oxygen uptake in the active limb during one-legged exercise was similar for patients and controls (0.52 (0.06) vs. 0.63 (0.06) l min-1), but it was 38% lower (P < 0.05) in patients than controls during exhaustive two-legged exercise. Arterial systemic oxygen delivery (cardiac output x arterial oxygen content), at peak exercise was highly correlated with peak one- and two-legged workload for both groups, explaining 70% of the difference in peak workload attained (P < 0.001). At peak two-legged exercise non-exercising tissues of the body in the male CHF patients with the largest limb muscle mass, received a blood flow of only 1.2 (0.7) 1 min-1. Mean arterial blood pressure at peak work in both test conditions was significantly lower for the patients than the controls. A higher sympathetic nerve activity in the patients, as evaluated by arterial noradrenaline concentration (NA) and leg NA spillover, contributed to maintain the perfusion pressure. CONCLUSIONS: Patients with moderate CHF can reach a peak skeletal muscle perfusion and a leg oxygen uptake comparable to that of healthy individuals when a sufficiently small muscle mass is activated. Exercise involving a larger muscle mass, for the patients in this study about 4 kg, markedly reduces peak leg blood flow, perfusion and oxygen uptake as well as blood flow to non-exercising organs and tissues.

Cardiac Output

Improved ventilation and decreased sympathetic stress in chronic heart failure patients following local endurance training with leg muscles.

BACKGROUND: Two-legged knee extensor training activates only about half the muscle mass used in traditional cycle ergometer training. With such an exercise model it is possible to achieve a substantial local training effect in spite of a restricted circulatory capacity. The present study sought to investigate the systemic effects of such local training on ventilation and neurohumoral activity in patients with moderate heart failure. METHODS AND RESULTS: Thirteen male patients with chronic heart failure (age 56 +/- 3 years, EF 28 +/- 3%) performed two-legged knee extensor exercises (about 4 kg of working muscle) for 15 minutes 3 times a week during 8 weeks at 65-75% of peak VO2 of a two-legged kick and were compared to a non-training control group (n = 7, age 62 +/- 3, EF 27 +/- 3%). Before and after the training period VO2, VCO2 and the minute ventilation (1/min) were determined at rest and at submaximal and maximal workloads. Also measured before and after training were two-legged knee extensor peak exercise capacity (W), strength (Nm), a 6-minute walking test (m), quadriceps femoris citrate synthase activity, plasma catecholamines, vasoactive amines and blood lactate during submaximal knee extension exercise, and perceived health-related quality of life. After training, VO2 and VCO2 were reduced at submaximal exercise by 20-30% (P < .01) but were unchanged at peak exercise. With training, the two-legged knee extensor peak exercise capacity increased by 38% (P < .01). The 6-minute walking gait velocity increased by 12% (P < .01) and skeletal muscle citrate synthase activity by 28% (P < .01). Training improved the quality of life (P < .01). After training, VO2 (P < .001), VCO2 (P < .001) and minute ventilation (P < .001) were reduced at the workload corresponding to the maximal workload before training. The ratio minute ventilation/VO2 was reduced (P < .05) after training at the before-training maximal workload. No change was observed in the control group with regard to two-legged peak exercise capacity or peak VO2. Plasma NPY was reduced both at rest and at submaximal exercise by 35% (P < .01), whereas noradrenaline was reduced only during exercise (P < .05). CONCLUSIONS: Local muscle training is effective in stable chronic heart failure and can improve, in addition to exercise capacity and quality of life, the ventilatory response, and decrease the sympathetic stress.

Adult

High proportion of type I fibres in thigh muscle of young dancers.

A previous study showed that adult female dancers have a high percentage of type I fibres in vastus lateralis, similar to that of endurance-trained female runners or female cross-country skiers. It is not known if dancers already at an early age are characterized by a high percentage of type I fibres or develop a high percentage of type I fibres as a consequence of dance training. Furthermore, the muscle fibre composition of male dancers has not previously been studied. Therefore the aim of the study was to analyse skeletal muscle fibre characteristics in 10-year-old and 20-year-old dancers of both sexes. Age-matched boys and girls whose physical activity was average for their age groups served as controls. Muscle biopsies for histochemical analysis were obtained from vastus lateralis using the percutaneous needle technique. The major finding of the present study was that the vastus lateralis of young dancers of both sexes had a higher percentage of type I fibres than that of controls. Moreover, the higher type I percentage was seen not only in 20 year olds, but also in 10 year olds, who had begun their dance training at a professional level only a few weeks earlier. No significant difference in this respect was found between female and male dancers. In conclusion, the muscle fibre type composition in young dancers of both sexes differs from that of the average individual of the same age and is characterized by a high percentage of type I fibres.

Adolescent

Long-lasting coronary vasoconstrictor effects and myocardial uptake of endothelin-1 in humans.

The effect of intravenous administration of the endothelium derived vasoconstrictor peptide endothelin-1 (ET-1 0.2. 1 and 8 pmol kg-1 min-1) on coronary blood flow in relation to plasma ET-1 as well as blood lactate and glucose levels were investigated in six healthy volunteers. Coronary sinus blood flow was measured by thermodilution. Administration of ET-1 elevated arterial plasma ET 35-fold, dose-dependently increased mean arterial blood pressure from 95 +/- 5 mmHg to 110 +/- 6 mmHg (P < 0.01) and reduced heart rate from 64 +/- 4 beats min-1 to 58 +/- 4 beats min-1 (P < 0.05) at 8 pmol kg-1 min-1. Coronary sinus blood flow was reduced maximally by 23 +/- 4% (P < 0.01) and coronary vascular resistance increased by 48 +/- 11% (P < 0.01). Coronary sinus oxygen saturation decreased from 35 +/- 1% to 22 +/- 2% at 2 min after the infusion (P < 0.01). A coronary constrictor response was observed at a 4-fold elevation in plasma ET. The reduction is coronary sinus blood flow lasted 20 min and coronary sinus oxygen saturation was still reduced 60 min after the infusion. Myocardial oxygen uptake or arterial oxygen saturation were not affected by ET-1. Myocardial lactate net uptake decreased by 40% whereas glucose uptake was unaffected. At the highest infusion rate there was a net removal of plasma ET by 24 +/- 3% over the myocardium (P < 0.05). The results show that ET-1 induces long-lasting reduction in coronary sinus blood flow via a direct coronary vasoconstrictor effect in healthy humans observable at a 4-fold elevation in plasma ET-1. Furthermore, there is a net removal of circulating ET-1 by the myocardium.

Adult

Comparable potent coronary constrictor effects of endothelin-1 and big endothelin-1 in humans.

BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstrictor produced from the precursor big ET-1 in endothelial cells. The coronary effects of these peptides in humans in vivo are unknown. Therefore, the effects of ET-1 and big ET-1 on coronary blood flow in relation to plasma ET-1 and big ET-1 levels were compared in healthy subjects. METHODS AND RESULTS: The peptides were infused intravenously at the rates of 0.2, 1, and 8 pmol/kg per minute. Each dose administered for 20 minutes except the highest dose of ET-1, which was administered for 10 minutes. ET-1 and big ET-1 evoked dose-related increases in mean arterial blood pressure from 93 +/- 4 to 107 +/- 4 mm Hg and from 89 +/- 2 to 122 +/- 5 mm Hg, respectively, at the highest dose. ET-1 and big ET-1 reduced coronary sinus blood flow, measured with thermodilution by a maximum of 25 +/- 4% and 28 +/- 8% and increased coronary vascular resistance by 50 +/- 9% and 107 +/- 26%, respectively. Coronary sinus, but not arterial, oxygen saturation was reduced in parallel with the coronary sinus blood flow. The effects of ET-1 and big ET-1 were similar at corresponding time points. During infusion of ET-1, a 19 +/- 5% extraction of ET-1 was observed over the coronary vascular bed (P < .05). Administration of big ET-1 elevated arterial plasma ET-1 levels by 2.4-fold, and after correction for the local extraction of ET-1, a myocardial production of ET-1 was observed. CONCLUSIONS: ET-1 and big ET-1 induce comparable increases in blood pressure and coronary constriction in humans in vivo. The results also suggest a net local removal of circulating ET-1 and big ET-1 and a local conversion of big ET-1 into ET-1 within the coronary vascular bed.

Adult

Markedly improved skeletal muscle function with local muscle training in patients with chronic heart failure.

BACKGROUND: Reduced heart pump function and skeletal muscle abnormalities are considered important determinants for the low physical exercise capacity in chronic heart failure. Because of reduced ventricular function, traditional physical rehabilitation may cause underperfusion and low local work intensity, thereby producing suboptimal conditions for skeletal muscle training. HYPOTHESIS: The study was undertaken to determine the effects of local exercise training, designed as one- or two-legged knee extensor training, on exercise capacity in patients with moderate chronic heart failure. Because such exercise models use only about one quarter to half the muscle mass used in cycle ergometer training, the influence of a restricted circulatory capacity should therefore be limited. Further, we aimed to determine whether or not chronic heart failure skeletal musculature abnormalities are counteracted with such training. METHODS: Fourteen patients with chronic heart failure [age 58 +/- 3 years, ejection fraction (EF) 28 +/- 4%] were randomized to two different training protocols three times a week for 8 weeks and compared with a nontraining control group (n = 7, age 62 +/- 3, EF 27 +/- 3%). Group 2L (n = 7) underwent simultaneous two-legged knee extensor training (about 4 kg working muscle) for 15 min at 65-75% of VO2 max of the two-legged kick. Group 1L (n = 7) trained each leg at a time for 15 min of continuous one-legged dynamic knee extensor work with the same training load per muscle mass, that is, at 35% of VO2 max of the two-legged kick (about 2 kg working muscle). Peak VO2 of two-legged knee extensor exercise (l/min), two-legged endurance (W), and strength (Nm) were determined before and after the training period. The activity of citrate synthase (CS) was estimated in tissue samples from the quadriceps femoris muscle. RESULTS: Peak VO2 did not change with training. Two-legged knee extensor endurance exercise capacity increased by an average of 40-50% (p < 0.01) in all training patients in both the 2L and 1L groups, while no change was observed in the control group. Depressed skeletal muscle CS activity increased by 25-35% in both training groups (p < 0.01). Strength increased by 16% in the 2L group after training (p < 0.05), while no change was seen in the 1L and control groups. CONCLUSIONS: Skeletal muscle changes in stable moderate chronic heart failure are not entirely irreversible. A major factor contributing to these changes and to exercise limitation is deconditioning. Local muscle training is efficient and can at least partially improve skeletal muscle function in these patients. Different degrees of local activation, that is, one- or two-legged knee extensor exercise, do not seem to differ in terms of their effect on exercise capacity. Depressed skeletal muscle oxidative capacity adapts to such physical training with increased activity to an extent not different from that for healthy volunteers.

Adaptation, Physiological

High intensity knee extensor training, in patients with chronic heart failure. Major skeletal muscle improvement.

Skeletal muscle adaptations to high intensity knee extensor strength and/or endurance training in patients with chronic heart failure were investigated. Eleven patients with chronic heart failure were randomized into two groups and exercised the m. quadriceps femoris 3 days/week for 8 weeks. After training, the maximal exercise intensity tolerated on the ergometer cycle was raised from 99 (32) to 114 (40) watts (W, P < 0.05) for all 11 patients. Peak dynamic knee extensor work rate showed the greatest increase after endurance training (40%, P < 0.01). Maximal dynamic and isometric strength were elevated by 40-45% (P < 0.05) after strength training. The cross-sectional area of m. quadriceps femoris was increased in the strength-trained legs (9%, P < 0.05), and the capillary per fibre ratio of m. vastus lateralis was raised by 47 and 58% in the endurance-trained legs (P < 0.05). The oxidative enzyme activity in m. vastus lateralis was significantly raised above 50% after endurance training, whereas glycolytic enzyme activity was unaltered. The peripheral skeletal musculature in patients with chronic heart failure adapts fairly quickly to high intensity knee extensor training. This results in a marked rise in local, and a small rise in total work capacity, indicating maintained plasticity of skeletal muscle in chronic heart failure patients.

Adaptation, Physiological

Exercise capacity in heart failure patients: relative importance of heart and skeletal muscle.

The knee extensor and the whole-body exercise capacities were measured in 11 chronic heart failure (CHF) patients and 11 healthy age- and sex-matched controls, and were related to ejection fraction and to biochemical and histochemical markers of the musculature. The CHF patients had a 39% lower maximal oxygen uptake measured on an ergometer cycle than the healthy controls (1.54 +/- 0.57 vs. 2.51 +/- 0.70 1 min-1, P < 0.001). The low exercise capacity was markedly related to the ejection fraction (r = 0.77, P < 0.001). The maximal strength of m. quadriceps femoris was 15% lower in the CHF patients than in the controls (P < 0.05). The cross-sectional area (CSA) of m. quadriceps femoris explained 55% (r = 0.74, P < 0.001) of the difference in strength between both groups. The endurance capacity of m. quadriceps femoris was 30% lower in CHF patients than in controls, partly as a result of the 25% lower capillary density (P < 0.05) and the 27% lower aerobic enzyme capacity (P < 0.05), as estimated by the citrate synthase activity, in the CHF patients. The citrate synthase activity correlated with the maximal oxygen uptake (r = 0.61, P < 0.05). Moreover, the ejection fraction, together with the CSA of m. quadriceps femoris, explained 75% (r = 0.86%, P < 0.01) of the difference in maximal oxygen uptake between CHF patients and controls. These results demonstrate that CHF patients have both a lower local and a lower whole-body work capacity than healthy controls. This is a function of a smaller leg muscle mass and a lower capillary density and mitochondrial enzyme capacity in the CHF patients; however, a lowered pump capacity of the heart is the factor which limits the exercise capacity the most.

Aged

Do highly physically active females have a lowered basal metabolic rate?

In several studies estimated energy intake has been found to be low compared with estimated energy expenditure in female athletes. It has therefore been suggested that female athletes may have a depressed basal energy expenditure (BMR). The main purpose of the present study was to explore this possibility by measuring BMR in physically extremely active females. Eight female dancers and 7 controls with low physical activity, all musicians, were studied; the variables measured included body weight, height, skinfold thickness and total body potassium. BMR was measured by indirect calorimetry. In conclusion, the present study lends no support to the idea of a lowered basal metabolic rate in female athletes as an explanation of the general finding of a lower estimated energy intake than energy expenditure in this type of subjects.

Adult

Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance.

BACKGROUND: Cardiac creatine levels are depressed in chronic heart failure. Oral supplementation of creatine to healthy volunteers has been shown to increase physical performance. AIM: To evaluate the effects of creatine supplementation on ejection fraction, symptom-limited physical endurance and skeletal muscle strength in patients with chronic heart failure. METHODS: With a double-blind, placebo-controlled design 17 patients (age 43-70 years, ejection fraction < 40) were supplemented with creatine 20 g daily for 10 days. Before and on the last day of supplementation ejection fraction was determined by radionuclide angiography as was symptom-limited 1-legged knee extensor and 2-legged exercise performance on the cycle ergometer. Muscle strength as unilateral concentric knee extensor performance (peak torque, Nm at 180 degrees/s) was also evaluated. Skeletal muscle biopsies were taken for the determination of energy-rich phosphagens. RESULTS: Ejection fraction at rest and at work did not change. Performance before creatine supplementation did not differ between placebo and creatine groups. While no change was seen in the placebo group compared to baseline, creatine supplementation increased skeletal muscle total creatine and creatine phosphate by 17 +/- 4% (P < 0.05) and 12 +/- 4% (P < 0.05), respectively. Increments were seen only in patients with < 140 mmol total creatine/kg d.w. (P < 0.05). One-legged performance (21%, P < 0.05), 2-legged performance (10%, P < 0.05), and peak torque, Nm (5%, P < 0.05) increased. Both peak torque and 1-legged performance increased linearly with increased skeletal muscle phosphocreatine (P < 0.05). The increments in 1-legged, 2-legged and peak torque were significant compared to the placebo group, (P < 0.05). CONCLUSIONS: One week of creatine supplementation to patients with chronic heart failure did not increase ejection fraction but increased skeletal muscle energy-rich phosphagens and performance as regards both strength and endurance. This new therapeutic approach merits further attention.

Administration, Oral

The effect of probucol on femoral atherosclerosis: the Probucol Quantitative Regression Swedish Trial (PQRST).

The Probucol Quantitative Regression Swedish Trial tested whether treatment of hypercholesterolemic persons with probucol for 3 years affected femoral atherosclerosis. The primary end point was the change in atheroma volume estimated as change in lumen volume of the femoral artery assessed by quantitative arteriography. Three hundred three patients with visible atherosclerosis were randomized to probucol 0.5 g, twice daily, or to placebo. All patients were given diet and cholestyramine, 8 to 16 g/day. Twenty-nine patients were excluded because of inadequate primary end point measurements. The mean age of the remaining 274 subjects (158 were men) was 55 years. Seventeen percent had intermittent claudication and 24% had angina pectoris. After 3 years, the probucol-treated patients had 17% lower serum cholesterol, 12% lower low-density lipoprotein cholesterol, 24% lower total high-density lipoprotein cholesterol, and 34% lower high-density lipoprotein2 cholesterol levels than control subjects. All lipoprotein differences between the treatment groups remained highly significant during the trial. There was no statistically significant change in lumen volume between the probucol and the control group. Furthermore, there was no difference between the treatment groups with regard to change in arterial edge roughness or amount of aorto-femoral atherosclerosis; neither were there any differences between the treatment groups with regard to change in ST-segment depressions on exercise tests or ankle/arm blood pressure (secondary end points). In the control group, lumen volume increased (p < 0.001) and roughness of the femoral artery decreased (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis

Muscle strength from adolescence to adulthood--relationship to muscle fibre types.

The aim of the present study was to reinvestigate muscle strength and the relationship to muscle fibre and the level of physical activity in adult men and women previously studied during adolescence. A group of 55 men and 26 women were tested for maximal strength (handgrip, Sargent jump and two-hand lift) and completed a questionnaire concerning physical activity during their leisure time (activity index) at the ages of 16 and 27 years. Biopsy specimens were taken from the vastus lateralis and analysed for fibre type (percentage of I, IIA, IIB) and fibre area (area I, area IIA, area IIB). The sex differences in strength increased from age 16 to 17 years. Body dimension, sex, percentage of type II, mean fibre area and the activity index contributed to explaining 50-75% of the strength at both ages. Different changes in relationship between fibre type composition and strength in women and men was seen with increasing age. In the women, the relationship between strength and the percentage of type II fibres changed with age (from 16 to 27 years of age) from a positive correlation (only Sargent jump) to negative correlations for all the strength tests, i.e. the more type I fibres the stronger the subject. A positive correlation between strength and the level of physical activity during leisure time was revealed in the women at both ages. The positive correlation between strength and type II fibres in the 16-year-old men had disappeared at age 27. No systematic relationships between strength and the level of physical activity were seen in the men at either 16 or 27 years of age. It is suggested that women may be more dependent on physical activity than adult men to develop strength and the percentage of type I fibres reflects the degree of physical activity among adult women but not among adolescent women.

Adolescent

The relation of coronary and peripheral arterial disease to the severity of femoral atherosclerosis in hypercholesterolaemia.

OBJECTIVES: The extent of atherosclerosis in the superficial femoral artery and the severity of arterial disease in the aorto-iliac and femoro-popliteal arterial districts were related to clinical diagnosis of coronary and peripheral atherosclerosis in hypercholesterolaemic patients. DESIGN: The study constitutes baseline cross-sectional data of a randomized double-blind clinical trial on Probucol, using both computer based and visual estimations of angiographies as endpoints. SUBJECTS: Two hundred and ninety men and women (mean age 54 years) with hypercholesterolaemia. MAIN OUTCOME MEASURES: Atherosclerosis was estimated with arteriographies. Lumen volume and edge roughness (vessel inner wall irregularity) of a 20 cm segment of the femoral artery were estimated by computer. A visual atherosclerosis score of the abdominal aorta to the popliteal arteries was made on both sides. RESULTS: Patients with peripheral arterial disease had significantly more advanced disease according to all three angiographic variables than those without symptoms of peripheral vascular disease. Both men and women with coronary artery disease had significantly lower femoral lumen volume and higher roughness values than patients without. Men with previous myocardial infarction had significantly higher mean visual scores of atherosclerosis than those without, while lumen volume and roughness did not differ in either sex. CONCLUSIONS: Femoral atherosclerosis is an expression of a generalized disease, associated with clinical symptoms of coronary artery disease. Femoral atherosclerosis is often accompanied by atherosclerosis also in the coronary arteries.

Adult

Cardiovascular responses during one- and two-legged exercise in middle-aged men.

Eight healthy and regularly physically active men, 44-69 years old, performed one- and two-legged dynamic knee extension exercise at increasing work intensities, including one leading to exhaustion. Leg blood flow increased linearly in relation to work rate, reaching a peak value of 5.1 +/- 0.4 l min-1. With a mean weight of quadriceps femoris of 2.2 +/- 0.1 kg, a peak perfusion of 2.3 +/- 0.1 l kg-1 min-1 was attained. The maximal leg oxygen uptake was 0.72 +/- 0.07 l min-1 (0.33 +/- 0.03 l kg-1 min-1). At submaximal work the elevation in limb oxygen uptake accounted for between 70 and 100% of the rise in pulmonary oxygen uptake. Comparing two- with one-legged knee extension the cardiac output was 1.5 l min-1 higher at each work level, reaching 13.7 +/- 0.7 and 12.3 +/- 1.0, respectively at exhaustion, leaving 3.5 and 7.2 l min-1 of blood flow to the remaining body (cardiac output--leg blood flow). The mean arterial pressure was 119 +/- 5 mmHg at rest and increased to 155 mmHg for both test modes at the maximal work rate. The femoral arterial and venous plasma concentrations of lactate, ammonia and noradrenaline were significantly higher for two-legged as compared with one-legged exercise at the maximal load performed. However, the rate of release per leg, for both lactate and ammonia, did not differ between the two test conditions. It is concluded that physically active middle-aged men, with a well-retained muscle mass, can maintain a high skeletal muscle perfusion, similar to that of young males. However, the blood flow is achieved with a higher mean arterial pressure and an elevated sympathetic activity, as reflected by noradrenaline in plasma and spillover from the exercising limb.

Adult

Exchange of purines in human liver and skeletal muscle with short-term exhaustive exercise.

The exchange of purines in liver and active skeletal muscle with short-term exhaustive exercise was investigated. Eight male subjects performed two similar 10-min bouts of exhaustive supine cycling, separated by 75 min of rest. Immediately after termination of the second bout, a tourniquet was applied to the upper part of the thigh for 10 min. After the first bout, the arterial concentration of hypoxanthine and uric acid increased from 4.1 +/- 0.3 (SE) to a peak value of 36.3 +/- 7.9 mumol/l (P < 0.05) and from 335 +/- 23 to a peak value of 421 +/- 28 mumol/l (P < 0.05), respectively. There was a net release of hypoxanthine from the muscle at 12 and 45 min postexercise and an uptake of hypoxanthine and inosine in the liver at 7 and 42 min postexercise. Uric acid was released from the liver at 7 and 42 min after exercise. Before the second exercise bout and at 2 and 10 min after the release of the tourniquet, there was a significant net uptake of uric acid by the muscle. The present study demonstrates that, after strenuous short-term exercise, the main source of plasma hypoxanthine is the muscle, with no net contribution of this purine from the liver. Hypoxanthine in the blood is taken up by the liver where most of it is converted to uric acid. After exercise and a short period of ischemia, uric acid is taken up by the muscle.

Adult