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Biomedical subjects

K Kjeldsen

Publications and source records attributed to K Kjeldsen.

At least 73 records · Page 4Linked to original sources

Exercise-induced hyperkalaemia can be reduced in human subjects by moderate training without change in skeletal muscle Na,K-ATPase concentration.

In 15 conscripts, venous plasma potassium was followed during exercise on a training bicycle before and after 10 weeks of moderate physical training and a putative relationship with skeletal muscle Na,K-ATPase was evaluated. Peak plasma potassium concentration obtained at exhaustion was 6.1 +/- 0.2 and 5.6 +/- 0.2 mmol l-1 (mean +/- SEM, n = 14, P less than 0.05) before and after training, respectively. Throughout the exercise period and within the first minutes of rest plasma potassium concentration was 0.2-0.5 mmol l-1 higher before than after training. Neither peak values nor peak rises in plasma potassium concentration before nor after training were correlated to the 3H-ouabain binding site (Na,K-ATPase) concentration in vastus lateralis muscle. The results indicate that net loss of potassium from the skeletal muscle pool during exercise is reduced after training, that the heart during exercise may be exposed to a smaller rise in plasma potassium concentration after training than before, and that moderate improvement of capacity to clear extracellular potassium during exercise may be due to increased activity of existing Na,K-pumps in resting skeletal muscle fibres. This may reduce muscle fatigue, increase physical performance and explain the paradoxical observation that, despite an increased catecholamine response, there is a reduced risk of cardiac events after training.

Adolescent↗

A surgical model to study in vivo efflux of cholesterol from porcine aorta. Evidence for cholesteryl ester transfer through the aortic wall.

We describe a surgical procedure in pigs which makes it possible to follow the influx into, the penetration through and the efflux from the arterial wall of labeled lipoproteins. After 4 h exposure of the luminal side of the arterial wall to labeled lipoproteins, labeled esterified cholesterol was found in all layers of the aortic wall, whereas labeled free cholesterol gained access only to the most luminal layer. The data suggest that at least 40%, if not 80-90%, of the cholesteryl ester that enters the aortic wall from the luminal side, passes through the entire wall and leaves the aortic wall through vasa vasorum and lymphatics. They also suggest that free cholesterol in the lipoproteins exchanges extensively with cellular free cholesterol while the lipoproteins penetrate through the most luminal layer. More than 90% of the labeled cholesteryl ester disappeared from the arterial wall during a cold chase period of 4 days. By the simultaneous use of [3H]cholesterol and [14C]cholesterol it was shown that only 10-20% of this disappearance can be explained by cholesteryl ester hydrolysis in the arterial wall.

Animals↗

Skeletal muscle Na,K-pump concentration in children and its relationship to cardiac glycoside distribution.

Skeletal muscle Na,K-pump (cardiac glycoside receptor) concentration was quantified in 18 0- to 8-year-old human subjects by vanadate facilitated [3H]ouabain binding to intact vastus lateralis samples obtained at autopsy. No age-dependent change in [3H]ouabain binding site concentration was observed. Mean value +/- S.E.M. was 268 +/- 17 pmol/g wet wt. (n = 18), range 182 to 433 pmol/g wet wt. At the age of 1 day, 3.5 month and 8 years and 8 months, unspecific uptake and retention of [3H]ouabain was 1.6, 1.4 and 1.5% of the total uptake and retention; release of specifically bound [3H]ouabain during the washout procedure took place with T 1/2 of 97, 90 and 73 hr; and apparent affinity constants for [3H]ouabain binding (KD) was 1.3 x 10(-8), 0.9 x 10(-8) and 1.2 x 10(-8) mol/l. [3H]Ouabain binding site concentrations and kinetics were in agreement with values from adults except that in children apparent affinity constant (KD) was 1.7 times the value in adults. The observation of no age-dependent changes in human skeletal muscle Na,K-adenosine triphosphatase concentration was at variance with the observations of such changes in animals. The total number of Na,K-pumps in the pool of skeletal muscles increased from 10 to 50 times that in the heart from birth to old age. The skeletal muscle pool of Na,K-pumps seems to constitute a distribution volume of importance during digitalization in children as well as adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Relation of left ventricular function and Na,K-pump concentration in suspected idiopathic dilated cardiomyopathy.

The possible relation between Na-K-pump concentration and left ventricular (LV) function was studied in 24 patients with suspected idiopathic dilated cardiomyopathy. This was done by measurement of 3H-ouabain binding to biopsies obtained during left-sided heart catheterization. In all patients light microscopy of biopsies was compatilel with dilated cardiomyopathy. Nineteen patients had impaired LV function as defined by NYHA/WHO and a Na,K-pump concentration of 331 +/- 19 pmol/g wet weight, whereas 5 patients had normal LV function and a Na,K-pump concentration of 559 +/- 62 pmol/g wet weight (p less than 0.001). The correlation between Na,K-pump concentration and ejection fraction was highly significant n = 24, r = 0.81, p less than 0.001). There was no correlation between volume fraction of collagen tissue and Na,K-pump concentration in the biopsies (n = 24, r = -0.08, p less than 0.80), indicating that the decrease in Na,K-pump concentration with dilated cardiomyopathy is not the simple outcome of increased fibrosis in the myocardium. The results indicate that the decrease in Na,K-pump concentration may be of importance for myocardial dysfunction and suggest a simple biochemical assessment of dilated cardiomyopathy by measurement of 3H-ouabain binding.

Adult↗

Reduced concentrations of potassium, magnesium, and sodium-potassium pumps in human skeletal muscle during treatment with diuretics.

Animal studies have shown that potassium depletion induced by diuretics or potassium deficient fodder leads to a selective decrease in the concentrations of potassium and in the concentration of sodium-potassium pumps in skeletal muscle. In 25 patients who had received diuretics for 2-14 years the mean concentrations of potassium, magnesium, and sodium-potassium pumps were measured in skeletal muscle biopsy specimens and were significantly lower than in those from a group of age matched controls. The reductions in all three variables were significant in those patients receiving diuretics for arterial hypertension as well as in those being treated for congestive heart failure. In 14 patients the mean muscle potassium concentration was below the control range, but only one of those was hypokalaemic (3.4 mmol/l), and 13 were receiving potassium supplements. In 15 patients the mean muscle magnesium concentration was below normal, and the mean muscle potassium and magnesium concentrations showed a linear correlation. In 12 patients in whom the mean muscle potassium concentration was below 80 mumol/g wet weight there was a linear correlation between the cellular potassium:sodium ratio and the concentration of 3H-ouabain binding sites indicating that potassium deficiency also leads to a down regulation of sodium-potassium pumps in human skeletal muscle. In spite of potassium supplements long term treatment with diuretics may lead to potassium and magnesium deficiencies, which are not detectable using the standard methods of serum analysis. The changes in concentrations of electrolytes and sodium-potassium pumps associated with treatment with diuretics may impair muscle function and potassium homoeostasis and interfere with the distribution of digitalis glycosides.

Adult↗

Homogeneity of [3H]ouabain-binding sites in rat soleus muscle.

Homogeneity or heterogeneity of rat soleus-muscle Na,K-ATPase (Na+ + K+-dependent ATPase) with respect to affinity for [3H]ouabain was evaluated. Since the standard method for measuring specific [3H]ouabain binding to rat skeletal-muscle samples includes subtraction of a value for non-specific [3H]ouabain uptake and retention, and a wash-out in the cold to remove [3H]ouabain from the extracellular phase, it was possible that these procedures could hide a class of [3H]ouabain-binding sites either with low affinity or with a rapid dissociation of [3H]ouabain. However, measurements of [3H]ouabain uptake and retention over the range 0.1-5 mM, as well as the omission of wash-out, gave no evidence for heterogeneity of [3H]ouabain-binding sites in rat soleus muscle. Furthermore, the observation of agreement between the uptake and retention of non-specific [3H]ouabain and of [14C]sucrose gave no evidence for the existence of a major pool of [3H]ouabain-binding sites with low affinity for [3H]ouabain. Assuming homogeneity, the total concentration of [3H]ouabain binding sites in soleus-muscle samples from 12-week-old rats is 278-359 pmol/g wet wt.

Animals↗

Na+,K+-ATPase concentration in rodent and human heart and skeletal muscle: apparent relation to muscle performance.

To investigate whether the sodium-potassium pump or Na+,K+-ATPase concentration in muscles is related to the capacity for muscle performance, the 3H-ouabain binding site concentration or 3-O-methylflourescein phosphatase activity was determined in samples of heart ventricular muscles from trained rats, cardiomyopathic hamsters, and human subjects. These methods have earlier been shown to quantify the Na+,K+-ATPase concentration in muscle tissue with high accuracy. When rats were swim trained for six weeks the heart ventricular muscle Na+,K+-ATPase concentration was increased by 20% (p less than 0.02) and the heart to body weight ratio by 14% (p less than 0.005). The increase in Na+,K+-ATPase concentration was only slowly reversible. After three weeks of deconditioning an increase of 12% (p less than 0.05) was still observed. In comparison skeletal muscle Na+,K+-ATPase concentration was increased by up to 46% (p less than 0.001) and decreased by up to 30% (p less than 0.005) after training and immobilisation respectively. Cardiomyopathic hamsters showed a reduction of 33% (p less than 0.005) in the heart ventricular Na+,K+-ATPase concentration compared with normal hamsters. This decrease was associated with a heart to body weight increase of 19% (p less than 0.01) and congestive heart failure. In six patients with a mean ventricular ejection fraction of 68% the mean Na+,K+-ATPase concentration in endomyocardial biopsy specimens obtained by left heart catheterisation was 505(41) compared with 322(32) pmol.g-1 wet wt (p less than 0.001) in nine patients with a mean ejection fraction of 29%. Taken together the present data indicate a relation between the Na+,K+-ATPase concentration and the capacity for muscle performance.

Animals↗

Immunity against diphtheria and tetanus in the age group 30-70 years.

In Denmark, childhood primary vaccination against diphtheria and tetanus has been recommended since 1950. No routine revaccinations or general vaccination of adults have been offered. In most other western countries revaccinations are recommended later in childhood. However, death still occurs from diphtheria and tetanus in countries with such vaccination programs although it is generally accepted that protective immunity can be obtained by vaccination. On this basis the immunity against diphtheria and tetanus was assessed in a random sample of 351 subjects in the age range 30-70 years. Diphtheria antitoxin titres were determined by in vitro neutralization technique using VERO cells. 26% had diphtheria antitoxin titres below protective level (0.01 international antitoxin units/ml serum). The highest number of unprotected against diphtheria was found among 30-39 year old women (68%) and 60-69 year old subjects (36%). Tetanus titres were determined by a combination of ELISA technique and an in vivo neutralization assay. 51% were unprotected against tetanus (less than 0.01 international antitoxin units/ml serum). The highest number of unprotected against tetanus was found among 60-69 year old subjects (68%) and especially among females in this age group (77%). To avoid epidemics of diphtheria in the future the immunity among adults must be raised within the coming years. Thus, revaccination must be recommended and high attendance ensured. One revaccination is sufficient only when complete primary vaccination is documented.

Adult↗

Quantification of rat sciatic nerve (Na+,K+)-ATPase by measurements of [3H]ouabain binding in intact nerve samples.

The (Na+,K+)-ATPase concentration in rat sciatic nerve was quantified by measurements of [3H]ouabain binding to intact nerve samples in a vanadate-Tris buffer. This gave values of 145-172 pmol/g wet weight in mature female rats. The methodological errors of the [3H]ouabain binding assay was identified, quantified and corrected for. The [3H]ouabain binding sites were homogeneous with respect to [3H]ouabain affinity with an apparent dissociation constant of 5 X 10(-8) mol/l, i.e. in the same range as in samples of skeletal muscles incubated at similar conditions. Post-mortem the [3H]ouabain binding site capacity in rat sciatic nerve decreased with a half-life time of 5 days, allowing measurements to be performed within 6 h after death with a reduction in [3H]ouabain binding sites of only 3%. When nerve samples were frozen the [3H]ouabain binding site concentration remained constant. An increase in sciatic nerve [3H]ouabain binding site concentration of 122% was seen from the 2nd to the 4th week of life followed by a decrease of 53% to the 12th week of life. In mature males the [3H]ouabain binding site concentration was 1.8 times that in nerves from age-matched female rats. Denervation caused a reduction of 61%, whereas K+ depletion or thyroid status has no effect on sciatic nerve [3H]ouabain binding site concentration.

Age Factors↗

Evaluation of vaccination requirements to secure continuous antitoxin immunity to tetanus.

To investigate minimal requirements for tetanus revaccination to secure continuous protection, recently recommended by WHO, 637 subjects with documented vaccination history were studied. Antitoxin concentration in serum relative to time corresponded to a steep decline in the first years after vaccination continuing exponentially. By multiple regression analyses duration of immunity after three-dose primary vaccination was calculated to be 5 years (upper 95% confidence limit of estimated risk of serum antitoxin concentration below 0.01 IU ml-1 still less than 0.1%). Serum antitoxin concentration relative to time after revaccination depended upon age at revaccination and interval from primary vaccination. When given in childhood 5 years after primary vaccination revaccination was calculated to offer protection for approximately equal to 21 years, but protection was considerably shorter when given to the elderly. Cross-sectional and longitudinal analyses were compared and statistical approaches were introduced which may be generally applicable for evaluation of vaccination programmes. It was concluded that a vaccination programme consisting of primary vaccination in infancy and one revaccination 5 years later will secure continuous protection to about the age of 25 years. This is considerably simpler than programmes recommended in many countries, in which risk of hyperimmunization is apparent.

Adult↗

Heart Na,K-ATPase activity in cardiomyopathic hamsters as estimated from K-dependent 3-O-MFPase activity in crude homogenates.

The hamster hereditary cardiomyopathy provides a unique model for the study of membrane abnormalities during chronic congestive heart failure. It is associated with intracellular calcium accumulation, mitochondrial calcification and cell necrosis. Previous studies have shown a decrease in Na,K-ATPase activity purified from ventricle sarcolemma. The present study demonstrates a decrease in K-dependent 3-O-methylfluorescein phosphatase (3-O-MFPase) activity from 1.93 to 1.30 mumol/g wet wt. or 33% in crude homogenates from the left ventricle of 7-months-old cardiomyopathic hamsters as compared to control animals. This represents an equivalent decrease in Na, K-ATPase activity. The values are several times higher than previously published for membrane fractions of myocardium from the hamster. Concomitantly, there was an increase in intracellular Na-concentration of the myocardium of 42% whereas the K-concentration was unchanged. The decrease in Na,K-pump concentration may be of importance for the increase in intracellular sodium and ensuing calcifying necrosis observed in the myocardium of cardiomyopathic hamsters. It is emphasized that quantification of the Na,K-ATPase or Na,K-pump should preferably be performed using crude homogenates.

Animals↗