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Biomedical subjects

L Kaijser

Publications and source records attributed to L Kaijser.

At least 73 records · Page 4Linked to original sources

Lung function in patients with prior poliomyelitis.

Lung volumes and spirometric flows, maximal respiratory pressures, lung diffusion capacity and blood gases were evaluated in 20 patients with prior poliomyelitis and compared with data from an age- and sex-matched control group. In the polio patients, static lung volumes and pulmonary flow capacity were significantly reduced to approximately 65% of the values of the control group. However, expiratory and inspiratory flows were normal in relation to lung volumes, while maximal respiratory pressures were significantly reduced in the polio patients. Static lung volumes and forced flows were correlated with the maximal respiratory pressures both in the polio patients and in the controls. However, when the muscle force in the polio patients decreased below a certain level, it became more important as a determinant of lung-flow capacity. The polio patients had a significantly increased PCO2 but a normal oxygen saturation and PCO2 was inversely correlated with the maximal respiratory pressures in the patients but not in the controls. The lung diffusion capacity was reduced in the polio patients compared to the controls, but less markedly than vital and total lung capacity. The findings indicate a restrictive respiratory dysfunction and alveolar hypoventilation most probably due to weakness of the respiratory muscles.

Adult↗

Is hypoxia a stimulus for synthesis of oxidative enzymes and myoglobin?

To compare two situations with similar magnitudes of mitochondrial substrate flux but different blood oxygen contents, one-legged training was employed. Ten healthy subjects trained one leg under normobaric conditions and the other under hypobaric conditions. At each session the subjects trained each leg for 30 min. The absolute work intensity was the same for both legs and was chosen to correspond to 65% of the average (right and left) pretraining one-legged maximal work capacity. There were three to four training sessions per week for 4 wk. Muscle biopsies from each leg were taken before and after training and analyzed for fiber types, capillaries, myoglobin, and oxidative and glycolytic enzymes. The most striking finding was a greater increase of citrate synthase activity under hypobaric conditions than under normobaric conditions. In addition, the myoglobin content increased in the leg trained under hypobaric conditions, whereas it tended to decrease in the normobarically trained leg. Because both legs were trained at the same intensity, the oxygen turnover and the substrate flux through the carboxylic acid cycle and the respiratory chain must have been of similar magnitude. Thus a difference in substrate flux is less likely to have caused the differences in enzyme activities and myoglobin content between training under normobaric and hypobaric conditions. Instead, the stimulus seems to be related to the blood oxygen content or tension.

Adult↗

Muscle oxidative capacity and work performance after training under local leg ischemia.

Healthy young men executed supine one-legged cycle training four times per week for 4 wk with legs and the cycle ergometer inside a pressure chamber, the opening of which was sealed by a rubber membrane at the level of the crotch. Each training session started by training one leg under ischemic conditions induced by increased chamber pressure (50 mmHg) at the highest intensity tolerable for 45 min. Then the other leg was trained with the same power profile but normal atmospheric chamber pressure. Before and after the training period, both legs executed one-legged exercise tests under both normal and increased chamber pressure and muscle biopsies were taken from the vastus lateralis. Ischemic training increased performance more than normal training, the difference being greater for exercise executed under ischemic conditions. The difference in performance increase between the legs was paralleled by a greater muscle citrate synthase activity in the ischemically than in the normally trained leg.

Adult↗

Myoglobin content and citrate synthase activity in different parts of the normal human heart.

Myoglobin (Mb) content and citrate synthase (CS) activity were determined in myocardial samples from nine human brain-dead organ donors with normal hearts. Six regions of each heart were analyzed: right and left atria, right ventricle, left ventricular subepicardium, subendocardium, and anterior papillary muscle. The Mb content was similar, whereas the CS activity was higher in the left than in the right heart at both atrial and ventricular levels. Mb content and CS activity were higher in ventricles than in atria. The subendocardial layer and papillary muscle of the left ventricle had a higher Mb content than the subepicardial layer, whereas CS activity was similar in these three locations. The results suggested a closer relationship between CS activity (oxidative potential) and work load than between Mb content and work load. Mb content may, instead, be related to intramuscular oxygen tension (PO2) on the basis of a comparison between our Mb data and those of others on regional variations in myocardial PO2.

Adolescent↗

Physical and psychological capabilities during substitution therapy with recombinant growth hormone in adults with growth hormone deficiency.

In a double-blind cross-over study with recombinant methionyl growth hormone (GH) and placebo during 12 weeks, the effect of GH substitution therapy (0.5-06 IU.kg-1.week-1) on physical performance, muscle strength, bone mineral density, and mood and cognitive functions was investigated in 6 GH-deficient adults. During GH substitution serum concentrations of insulin-like growth factor-I and procollagen-III peptide increased in all 6 patients, whereas concentrations of serum urea decreased. Five of the patients identified the GH period and reported improved well-being with increased mental alertness and vitality and improved physical capacity and muscle strength. There was, however, no change of the isokinetic muscle strength during GH substitution therapy, and the working capacity on the bicycle ergometer was just slightly improved in some patients. The bone mineral density was low and unchanged in all patients. Mood and cognitive functions did not change during GH therapy. A reversible fluid retention was observed in one patient during the GH period. In conclusion, short-term GH substitution therapy to GH-deficient adults induced a subjective improvement of general well-being. Longer treatment periods will be necessary to establish the effect on physical capacity, muscle strength, bone mineral density, and mood and cognitive functions.

Adult↗

Lactate dehydrogenase and its isoenzyme activities in different parts of the normal human heart.

Activity and distribution of lactate dehydrogenase (LD) and its isoenzymes (LD1-5) were determined and both the heart (H) and muscle (M) subunit activities were calculated in myocardial samples from six brain dead human organ donors with normal hearts. Ten parts of each heart were analysed. LD1-3 were found to be the main LD isoenzymes. The LD1 activity predominated in all parts analysed. The activities of total LD, H subunit and LD1 increased from atria and auricular appendages via the right ventricle to the left ventricle. The H subunit activity varied more than twofold and the M subunit activity by only 20% between different locations of the heart. The left ventricular papillary muscle was found to have higher activities than other locations of both H and M subunits. It is concluded that the isoenzyme profile could be a metabolic adaptation to divergent work demand on the different heart chambers.

Adaptation, Physiological↗

Theophylline decreases pain in the ischaemic forearm test.

To study the hypothesis that endogenous adenosine is a mediator of the ischaemic pain sensation, the effect of the adenosine receptor blocker theophylline (5.5 mg of the ethylendiamine salt.kg-1 intravenously) was tested in a placebo controlled double blind cross over study (placebo/theophylline/placebo or placebo/placebo/theophylline) in five healthy volunteers. Ischaemic work was performed with a spring loaded hand ergometer (1 Hz). The pain sensation was continuously reported using the Borg scale. Blood flow was measured by occlusion plethysmography. Pain was reported 18 (SEM 2.4) s after starting the ischaemic work and increased continuously to a maximum after 129(18) s (placebo). Theophylline at a plasma concentration of 75(7) mumol.litre-1 decreased the pain sensation in relation to working time. With theophylline, 12(3)% more work (p less than 0.01) was performed for the same reported pain estimate. Blood flow increased from a basal level of 52(9) to 495(55) ml.min-1.100 ml-1 30 s after work and returned to normal within 30-40 min. Theophylline did not affect blood flow. In conclusion, theophylline has a small but significant inhibitory effect on the ischaemic pain sensation compatible with a hyperalgesic effect of adenosine.

Adult↗

Effect of oral administration of nifedipine on neuropeptide Y- and noradrenaline-induced vasoconstriction in the human forearm.

Neuropeptide Y (NPY) has recently been shown be co-released with noradrenaline (NA) from sympathetic nerves and to cause arterial vasoconstriction in experimental animals and man. The effect of a single oral dose (10 mg capsule) of nifedipine on NPY- and NA-induced reductions of forearm blood flow (FBF) was studied in seven healthy volunteers. Intra-arterial infusions of NPY and NA into the brachial artery before nifedipine caused dose-dependent reductions in FBF with threshold doses of 0.2 and 0.03 nmol x min-1, respectively. The response to NPY was slower in onset and more long lasting than that to NA. Forty-five min after administration of nifedipine, FBF and heart rate had increased significantly (by 49% and seven beats x min-1, respectively, P less than 0.001), while no significant change was observed in systemic blood pressure. The NPY-induced decrease in FBF was slightly but significantly attenuated after compared to before nifedipine (19 +/- 6 vs. 28 +/- 5% at 1.0 nmol NPY x min-1; P less than 0.01). The response to NA was, however, not significantly altered by nifedipine. In conclusion, the NPY-induced reduction in FBF in man was only slightly prevented and the NA response not significantly affected by oral nifedipine administration in a clinically used dose. This suggests that this calcium antagonist, in the present dosage, does not, to any major extent, inhibit the vasoconstrictor effect of NPY or NA in man in vivo.

Administration, Oral↗

Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: Probucol Quantitative Regression Swedish Trial (PQRST): a status report.

The Probucol Quantitative Regression Swedish Trial is being performed to investigate the effects of probucol on atherosclerosis in the femoral artery. Probucol is combined with cholestyramine and dietary management in hypercholesterolemic patients, and the effects of atheroma developing in the femoral artery will be followed by a quantitative angiographic technique. A randomly selected control group is also being managed by dietary therapy and cholestyramine, but receives placebo instead of probucol. The treatment time in this double-blind trial is 3 years, and femoral angiography is performed yearly. Detailed lipoprotein and apolipoprotein analysis are performed at monthly intervals. The basic study design is described here, and some results from the open prerandomization phase of the study are presented.

Arteriosclerosis↗

Effects of training at simulated altitude on performance and muscle metabolic capacity in competitive road cyclists.

Differences between the effects of training at sea level and at simulated altitude on performance and muscle structural and biochemical properties were investigated in 8 competitive cyclists who trained for 3-4 weeks, 4-5 sessions/week, each session consisting of cycling for 60-90 min continuously and 45-60 min intermittently. Four subjects, the altitude group (AG), trained in a hypobaric chamber (574 torr = 2300 m above sea level), and the other four at sea level (SLG). Before and after training work capacity was tested both at simulated altitude (574 torr) and at sea level, by an incremental cycle ergometer test until exhaustion. Work capacity was expressed as total amount of work performed. Venous blood samples were taken during the tests. Leg muscle biopsies were taken at rest before and after the training period. AG exhibited an increase of 33% in both sea level and altitude performance, while SLG increased 22% at sea level and 14% at altitude. Blood lactate concentration at a given submaximal load at altitude was significantly more reduced by training in AG than SLG. Muscle phosphofructokinase (PFK) activity decreased with training in AG but increased in SLG. All AG subjects showed increases in capillary density. In conclusion, work capacity at altitude was increased more by training at altitude than at sea level. Work capacity at sea level was at least as much improved by altitude as by sea level training. The improved work capacity by training at altitude was paralleled by decreased exercise blood lactate concentration, increased capillarization and decreased glycolytic capacity in leg muscle.

Adolescent↗

Adenosine injection into the brachial artery produces ischaemia like pain or discomfort in the forearm.

To determine whether pain or discomfort could be provoked by adenosine in skeletal muscle and, if so, whether it was dependent on the vasodilatation produced by adenosine, eight male volunteers were given intra-arterial bolus injections of adenosine and glyceryl trinitrate into the forearm. Local pain was assessed on a scale rate, forearm blood flow was measured by venous occlusion plethysmography, and blood was sampled simultaneously from the deep vein of the same arm. Five different doses of adenosine, ranging between the maximum tolerable and the lowest producing pain or discomfort, were given intra-arterially in random order and repeated in reverse order. Glyceryl trinitrate was given intra-arterially in increasing doses from 1 to 20 micrograms. Pain or discomfort began 12(1)(SEM) s after administration reached its maximum after 17(1) s, and disappeared after 40(2) s. Pain or discomfort appeared 8(1) s (p less than 0.001) after the first recorded increase in forearm blood flow, whereas maximum pain or discomfort preceded maximal forearm blood flow by 5(1) s (p less than 0.001). The flow remained increased after the disappearance of pain or discomfort. The effects of adenosine on pain or discomfort and vasodilatation were dose dependent. Glyceryl trinitrate provoked a similar increase in flow to that with adenosine without producing pain or discomfort. Arterial occlusion for 5 min at rest or forearm exercise with arterial occlusion increased forearm blood flow to the same extent as the maximum dose of adenosine. In addition, ischaemic work slightly increased the plasma concentration of adenosine. The pain or discomfort after ischaemic work was not considered different from the adenosine provoked pain or discomfort by four of the subjects. It is concluded that the symptoms did not appear to be dependent on vasodilatation and therefore adenosine may contribute to ischaemic pain or discomfort.

Adenosine↗

Alpha-adrenoceptor influence on plasma levels of neuropeptide Y-like immunoreactivity and catecholamines during rest and sympathoadrenal activation in humans.

Antecubital venous plasma neuropeptide Y-like immunoreactivity (NPY-LI) and catecholamines were analyzed in six healthy volunteers performing a graded bicycle exercise without medication and after acute administration of clonidine, phentolamine, and nifedipine. During the control exercise, plasma noradrenaline (NA), adrenaline (A), and NPY-LI increased to 17-, 7-, and 3-fold the resting values, respectively, at a maximal workload. Clonidine (300 micrograms p.o.) reduced resting and exercising heart rate (HR) and systolic blood pressure (SBP). Plasma NA at rest decreased and NA, A, and NPY-LI were 40-60% lower during the exercise after clonidine compared to the control. Phentolamine (0.07 mg X kg-1 every 10 min i.v.) and nifedipine (20 mg p.o.) increased HR and reduced SBP during the exercise. Plasma NA at rest was elevated threefold and the exercise-induced increases in NA and A were also enhanced after phentolamine. Plasma NPY-LI at rest was unchanged by phentolamine, while it was increased five-fold, as compared to the control, at the highest workload. Nifedipine slightly enhanced plasma NA and NPY-LI but not A during exercise. It is suggested that NPY is released mainly at high levels of sympathetic activity and that blood-pressure-lowering drugs acting on alpha adrenoceptors acutely influence the release of both NA and NPY-LI from sympathetic nerves in humans.

Adrenal Glands↗

Calf muscle adaptation in intermittent claudication. Side-differences in muscle metabolic characteristics in patients with unilateral arterial disease.

The adaptation of enzyme activities, notably in the oxidative metabolism, and of prerequisites for tissue transport of oxygen in the claudication leg was evaluated by comparing muscle biopsies from the gastrocnemius muscle of the claudication and the symptom-free leg of seven patients with unilateral claudication. The claudication leg had higher activities of a marker enzyme for mitochondrial oxidative capacity, citrate synthase (CS), as well as of the MB and the mitochondrial isoenzyme of creatine kinase (CK), which are considered to be involved in the transfer of high energy phosphate from the mitochondria to the resynthesis of ATP in the cytoplasm. The difference between claudication and healthy leg in activities of these CK isoenzymes were well correlated with the corresponding side difference in CS activity. No significant differences between claudication and healthy leg were found in distribution of muscle fibre types or fibre dimension, capillary density or myoglobin content, nor was there any side difference in phosphofructokinase or lactate dehydrogenase. Side differences tended to be greater in those patients with the most advanced obstructive arterial disease as estimated from non-invasive pressure measurements. It is concluded that in reasonably physically-active patients, the mode of ischaemia to which the claudication leg is subjected leads to a metabolic adaptation characterized by increased activities of enzymes involved in the oxidative metabolism, but no significant adaptation of either the conditions for local oxygen transport, as estimated by myoglobin content, and capillary density, or capacity for anaerobic metabolism.

Aged↗

Myocardial turnover of plasma free fatty acids during angina pectoris induced by atrial pacing.

Myocardial extraction of free fatty acids (FFA), together with glucose, lactate, pyruvate, glycerol and oxygen was determined by simultaneous sampling of blood from an artery (a) and the coronary sinus (cs) at rest and during chest pains induced by atrial pacing in seven fasting male patients with ischaemic heart disease. Results were compared to those, at rest and during pacing at heart rate 140 beats min-1, in ten healthy men of similar age. A continuous i.v. infusion of 14C oleate and 3H palmitate enabled the calculation of simultaneous myocardial uptake and release of FFA as well as of the fraction of extracted FFA which underwent direct oxidation. During chest pain lactate net extraction decreased to become, in some patients, negative. FFA extraction, as estimated from the fractional extraction of labelled fatty acid was likewise decreased, while the a-cs O2 difference was not significantly altered. The fractional oxidation of extracted FFA was increased, whereas the calculated fatty acid release from the heart was unaltered. The increase in fractional oxidation was quantitatively correlated with the decrease in lactate extraction suggesting that it was related to the degree or extent of ischaemia. It was also proportional to the decrease in FFA extraction. Thus, in patients with angina pectoris the ischaemic myocardium may be subjected to a limitation not only with regard to oxygen but also substrate flux into the myocardial cells.

Angina Pectoris↗

Coenzyme Q10 content in different parts of the normal human heart.

Coenzyme Q10 (CoQ10) and citrate synthase (CS) activities were analysed in the myocardium of brain-dead organ donors (14-40 years). Different parts of the heart were studied: right and left auricular appendage, right and left atrium, right ventricle (septum and free wall) and left ventricle (septum, free wall, and papillary muscle). Freeze-dried, dissected myocardial samples were analysed for CoQ10 content by HPLC and CS activity by fluorometric technique. CoQ10 content in the normal human myocardium was lowest in auricular appendages and atria (0.25 +/- 0.06 mg X g-1 dry muscle), intermediate in right ventricle (0.37 +/- 0.05 mg X g-1 dm) and highest in left ventricle (0.42 +/- 0.07 mg X g-1 dm). CS activity showed the same relationship between these locations as CoQ10. The results suggest that there exist differences in CoQ10 content between different parts of the normal human myocardium. These differences were closely related to the differences in CS activity between corresponding parts. The differences between different parts of the heart may be related to divergent work demand, and the constant relationship between CS and CoQ10 may be related to their coupling to the mitochondrial oxidative metabolism.

Adult↗

Autonomic cardiovascular responses in antecedent poliomyelitis.

Autonomically mediated cardiovascular responses were evaluated in 20 subjects with antecedent poliomyelitis and compared to data from an age- and sex-matched control group. The polio subjects had a lower heart rate response to the Valsalva manoeuvre but the same respiratory sinus arrhythmia as the controls. From this it is concluded that the polio subjects had a normal vagal function. The polio subjects had a greater initial heart rate increase but the same blood pressure response to the orthostatic position as the controls. This indicates a normal function of the sympathetic nerves. The greater heart rate increase is most likely caused by a displacement of blood to the legs because of muscle atrophy. The polio subjects had a smaller blood flow increase as an initial response to an isometric handgrip than the controls. This might be attributed to a reduced beta-adrenergic vasodilation, possibly due to a reduced central vasomotor drive. It is concluded that subjects with antecedent poliomyelitis have no significant dysfunction of the peripheral autonomic nerves. Thus, there is no deterioration of the peripheral autonomic nerve function in parallel with the progressive muscle atrophy and paralysis earlier described in post-polio subjects.

Adult↗

Vasoconstrictor effects in vivo and plasma disappearance rate of neuropeptide Y in man.

Vascular effects of neuropeptide Y (NPY) and noradrenaline (NA) were studied in six human volunteers. Systemic infusion of human NPY for 40 min (5 pmol X kg-1 X min-1) increased arterial plasma NPY-like immunoreactivity (NPY-LI) from 12 +/- 2 to 356 +/- 30 pM. This concentration caused no systemic cardiovascular effects. The disappearance curve for NPY-LI was biphasic; the slopes of the two phases corresponding to half lives of 4.1 +/- 0.4 and 20 +/- 2 min respectively. Close i.a. infusion of human NPY in the forearm caused a slowly developing and dose dependent decrease in forearm blood flow (FBF) and increase in venous tone with maximal values of 44 +/- 6 and 235 +/- 81% of control respectively at 5 nmol X min-1. The corresponding values for NA (5 nmol X min-1) were 21 +/- 9 and 489 +/- 78% of control. A threshold concentration for a decrease in FBF was obtained at a plasma NPY-LI of 3.7 +/- 0.6 nM. The decrease in FBF caused by NPY was maintained for a much longer period compared to that of NA.

Adult↗

Increased removal rate of exogenous triglycerides after prolonged exercise in man: time course and effect of exercise duration.

Ten healthy young men exercised for 1.5 and 3 hours, respectively, 4 to 6 weeks apart at the same work intensity, corresponding to 77% of the individual maximal heart rate. In the fasting state 1 mL of 10% Intralipid/kg body weight was injected IV, the fractional removal rate was calculated (k2-value), and fasting lipid and apolipoprotein C-I, C-II, and CIII concentrations were determined one day before, immediately before, immediately after, and one day after the exercise: measurements were also made two and three days after the three-hour session. An increase of the k2-value was found only the day after the three-hour exercise (+66%, P less than .01), while after the 1.5-hour exercise the k2-value was not changed. One and two days after the three-hour exercise the fasting serum triglyceride concentration was significantly decreased by 33% and 16%, respectively. Serum triglyceride concentration was decreased also the day after the shorter session (-17%, P less than .05). Decreases in serum cholesterol concentrations were significant after both exercise bouts, but the significance disappeared if corrections for the changes in calculated plasma volume were made. Serum level of C apolipoproteins was decreased one day after the three-hour exercise, while it was not changed after the shorter exercise. This study shows that prolonged exercise produces an increase in the removal rate of Intralipid triglycerides from the bloodstream, that this change is related to the duration of exercise, and that some time is required following the exercise, before it is manifest.

Adult↗