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Biomedical subjects

K Sahlin

Publications and source records attributed to K Sahlin.

At least 109 records · Page 6Linked to original sources

Regulation of glycogenolysis in human muscle in response to epinephrine infusion.

The regulation of glycogenolysis in human muscle during epinephrine infusion has been investigated. The content of cAMP in resting muscle was 2.7 +/- 0.7 (SD) mumol . kg dry muscle-1 and increased threefold during the first 5 min of infusion. Total glycogen phosphorylase and glycogen synthase activities were unchanged during the infusion. The proportion of phosphorylase in the a form in the basal state was estimated to be at least 22.5% and during infusion 80-90%. During infusion, synthase I activity decreased. The muscle glycogen content was 340 mmol . kg dry wt-1 and decreased during the first 2 min of infusion at a rate of 11.0 mmol glycosyl units . kg dry wt-1 . min-1. Prolonged infusion resulted in a much lower glycogenolytic rate, even though most of the phosphorylase was still in the a form. Accumulation of hexose monophosphates and lactate followed the changes in glycogen. It was concluded that despite the almost total transformation of phosphorylase to the a form, the in vivo activity was maintained at a low level. It is suggested that this may be due to a low concentration of inorganic phosphate at the active site of the enzyme.

Adolescent↗

The contents of high-energy phosphates in different fibre types in skeletal muscles from rat, guinea-pig and man.

1. The contents of high-energy phosphates at rest have been measured in skeletal muscles with different fibre-type composition from rat, guinea-pig and man. All muscles studied biochemically have been characterized histochemically. 2. Fast-twitch muscles had a higher ATP/ADP ratio than slow-twitch muscles and, with the exception of the tongue in the rat, higher contents of ATP and phosphocreatine. 3. There was an inverse relationship between the content of phosphocreatine and the stainability for succinyl dehydrogenase, which is a marker enzyme for oxidative capacity. 4. The biochemical and histochemical data are discussed in relation to known morphological and functional properties of the different muscle-fibre types. It is concluded that fast-twitch fibres have a high ATP/ADP ratio favouring a fast acceleration of energy production. The content of phosphocreatine seems to be related to the glycolytic capacity but not to the contraction time. In addition to being an immediate energy source, phosphocreatine functions as a buffer against lactic acidosis.

Adenine Nucleotides↗

Regulation of glycogenolysis in human muscle at rest and during exercise.

The regulation of glycogenolysis in human muscle during isometric and dynamic exercise has been investigated. Total glycogen phosphorylase and synthase activities were unchanged during exercise. The fraction of phosphorylase in the alpha form at rest was estimated to be 20%, but the data indicate that the in vivo activity was low and critically dependent on the concentration of inorganic phosphate (Pi) in the muscle. Phosphorylase alpha increased initially 2.4-fold during isometric contraction and 1.6-fold during maximal bicycle exercise but reverted to or below the resting value at fatigue/exhaustion. At rest synthase I was 17-48% of the total activity but decreased during exercise to about half of this value. The reciprocal changes in phosphorylase and synthase correlate with the enhanced rate of glycogenolysis during exercise. Michaelis constant (Km) for Pi was 27 mmol . l-1 for phosphorylase alpha and 7 mmol . l-1 for alpha + b. From consideration of the changes in Pi during exercise (to 20-30 mmol . l-1) it was concluded that Pi is one of the main factors determining phosphorylase activity and provides a link between phosphocreatine breakdown and glycogen utilization in muscle.

Adult↗

Glycolytic intermediates in human muscle after isometric contraction.

Isometric contraction of the quadriceps muscle sustained to fatigue with a force of 66% of the maximum voluntary contraction force resulted in a mean glycogen utilization of 80.4 (S.D. 58.4) mmol glucosyl units/kg dry muscle (d.m.) and an accumulation of glycolytic intermediates and glucose corresponding to 82.9 (S.D. 17.5) mmol glucosyl units/kg d.m. Accumulation of hexose phosphates (principally glucose 6-phosphate) accounted for 35.4% (S.D. 4.1) of the total increase and lactate for 59.3% (S.D. 2.8). During a 4 min recovery period glucose 6-phosphate content showed a linear decrease with a half time of 2.0 min and lactate decreased exponentially with a half time of 2.5 min. The rate of lactate disappearance from the muscle was approximately 4 times as fast as that observed previously after maximal bicycle exercise. This was probably due to a lower lactate concentration in blood after isometric contraction resulting in a larger muscle-blood gradient for lactate. Muscle content of free glucose was increased after contraction and increased further during recovery. It is concluded that the glucose increase is confined to the intracellular pool and is an effect of hexokinase inhibition by accumulated glucose 6-phosphate. Occlusion of the local circulation after the contraction inhibited the recovery processes for lactate and glucose 6-phosphate.

Energy Metabolism↗

Effect of short-term CO2-breathing on the CO2 content and intracellular pH in skeletal muscle of man.

Subjects inhaled air with 8% CO2 for 10 min. Carbon dioxide tension in arterial blood increased rapidly from about 5 kPa to 7 kPa, whereas venous CO2 tension increased more slowly, reaching the arterial value at the end of the CO2-breathing period. Muscle content of total CO2 (HCO-3, H2CO3, solubilized CO2) did not change during CO2-breathing or the following 15 min of recovery. However, when CO2-breathing was combined with light bicycle exercise, total CO2 increased by 30%. This could be an effect of both increased local circulation and increased endogenous CO2 production in the muscle. It is concluded that 10 min CO2-breathing alone is insufficient to affect CO2 content and intracellular pH in resting skeletal muscle.

Acid-Base Equilibrium↗

Effects of lactic acid accumulation and ATP decrease on muscle tension and relaxation.

The present study was undertaken to evaluate the effect of lactic acid accumulation on peak tension and relaxation rate of the isometric twitch. Isolated extensor digitorum longus muscle from rat was stimulated electrically at a frequency of 2/s under anaerobic conditions. Comparison was made with muscles in which glycolysis was blocked with iodoacetic acid (IAA). Stimulation of unpoisoned muscles for 3 min decreased tension to 50% and increased relaxation time to 250% of the initial value. Lactate increased 15-fold, and muscle pH decreased from 7.10 to 6.76. Stimulation of IAA-poisoned muscles for 1 min decreased tension to 50% but did not increase the relaxation time. Stimulation of IAA-poisoned muscle resulted in a pronounced decrease (about 50%) of the ATP and total adenine nucleotide content in muscle, whereas only a small decrease (10-15%) occurred in unpoisoned muscle. The main findings in the present study were that tension decline in unpoisoned muscle is closely related to decrease in muscle pH and increase in ADP but not to ATP content per se and that slowing of relaxation rate is closely related to decrease in muscle pH but not to muscle content of ATP or creatine phosphate.

Adenosine Diphosphate↗

Glycolytic and oxidative energy metabolism and contraction characteristics of intact human muscle.

It is proposed that glycolytic rate may be measured as lactate accumulation after electrical stimulation of the quadriceps femoris muscle under anaerobic conditions. The ratio of glucose 6-phosphate to lactate is an internal monitor of the glycolytic pathway. The phosphocreatine/lactate ratio links glycolysis and the creatine kinase reaction and could be used to distinguish abnormalities in energy metabolism. The rate of resynthesis of phosphocreatine after stimulation when the circulation is restored should be measure of oxidative phosphorylation. The relaxation rate seems to be a mechanical index of the metabolic state of the muscle.

Adenosine Triphosphate↗

Resynthesis of creatine phosphate in human muscle after exercise in relation to intramuscular pH and availability of oxygen.

After exhaustive exercise the muscular store of creatine phosphate (CP) is almost completely depleted. The resynthesis of CP during recovery normally occurs rapidly, but is totally inhibited if the local circulation to the muscle is occluded. The limiting factor for CP resynthesis which could be a low intramuscular pH or availability of oxygen has been investigated in the present study. Biopsies from musculis quadriceps femoris of man were analyzed for pH, ATP, ADP, CP, creatine, lactate and pyruvate. It was shown that resynthesis of CP only occurs when the blood supply to the muscle is intact. From this it was concluded that the creatine kinase reaction is at a steady state or at equilibrium during the period of recovery. The influence of oxygen on the resynthesis of CP was investigated by incubating muscle samples taken after a fatiguing isometric contraction in atmospheres of oxygen and nitrogen, respectively. During 15 min incubation in oxygen CP was resynthesized from a starting value of 4% to 68% of the normal value at rest. No resynthesis was observed when parallel muscle samples were incubated for the same time in nitrogen. It is suggested that the initial fast phase of CP resynthesis is limited by the availability of oxygen whereas the subsequent slow phase is limited by the hydrogen ion transport out from the muscle.

Adenosine Diphosphate↗

Intracellular pH and bicarbonate concentration in human muscle during recovery from exercise.

Eight subjects exercised on an ergometer until exhaustion. Femoral venous blood was analyzed for lactate, pyruvate, protein, electrolytes, and acid-base parameters. Muscle samples taken during the recovery period from m. quadriceps femoris were analyzed for water, electrolytes, lactate, and acid-labile CO2. Water content in the muscle biopsy sample was increased after exercise to 78.7 +/- 0.5% compared with the normal 76.7 +/- 0.8% at rest. The distribution of water between the extra- and intracellular space was calculated by the chloride method. In spite of elevated PCO2 in femoral venous blood the content of acid-labile CO2 was decreased in muscle after exercise. One minute after termination of exercise muscle CO2 was about half of the normal content at rest. During the recovery period muscle CO2 increased but was 20 min after termination of exercise still significantly below the value at rest. Intracellular pH (pHi) and bicarbonate concentration ([HCO3-]i) in muscle have been calculated. The validity of the assumptions underlying the calculations are thoroughly discussed. pHi decreased from the normal value at rest, 7.00 +/- 0.06 (mean +/- SD), to about 6.4 after exercise. [HCO3-] decreased from 10.2 +/- 1.2 mmol/l at rest to about 3 mmol/l after exercise. The changes are the greatest so far reported for an in vivo situation. After 20 min recovery pHi was almost the same as at rest, whereas bicarbonate was still well below.

Acid-Base Equilibrium↗

Intracellular pH and bicarbonate concentration as determined in biopsy samples from the quadriceps muscle of man at rest.

1. A method for measuring intracellular pH and bicarbonate concentration of human muscle is described. 2. Muscle biopsies from the quadriceps muscle of 13 healthy subjects at rest were analysed for acid-labile carbon dioxide and volume of extra- and intra-cellular water. Extracellular water volume was estimated from the chloride content and intracellular water volume from the potassium content, or alternatively derived from the sample weight. 3. The measured total carbon dioxide content in muscle was 9-84+/-1-39 mmol/kg. 4. Assuming a normal membrane potential (88 mV) and PCO2 of muscle equal to venous blood, calculated intracellular pH was 7-00+/-0-06 and intracellular bicarbonate concentration was 10-2+/-1-2 mmol/l of water.

Adult↗

Phosphagen and lactate contents of m. quadriceps femoris of man after exercise.

Muscle biopsies were taken from the m. quadriceps femoris of man immediately after termination of dynamic and isometric exercise. These were analyzed for adenosine triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-phosphate (AMP), phosphorylcreatine (PC), creatine, pyruvate and lactate. Regardless of type, intensity, and duration of the preceding exercise, a general pattern of the relation between high-energy phosphates and lactate content could be observed. PG showed a nonlinear relationship to the muscle lactate content. The ratio of ATP to ADP appeared to decrease linearly when lactate content increased. The relationships are believed to be the consequence of a steady-state condition where muscle pH is one of the major determining factors.

Adenine Nucleotides↗

The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man.

The time course of phosphorylcreatine (PC) resynthesis in the human m. quadriceps femoris was studied during recovery from exhaustive dynamic exercise and from isometric contraction sustained to fatigue. The immediate postexercise muscle PC content after either form of exercise was 15-16% of the resting muscle content. The time course of PC resynthesis during recovery was biphasic exhibiting a fast and slow recovery component. The half-time for the fast component was 21-22s but this accounted for a smaller fraction of the total PC restored during recovery from the isometric contraction than after the dynamic exercise. The half-time for the slow component was in each case more than 170 s. After 2 and 4 min recovery the total amount of PC resynthesized after the isometric exercise were significantly lower than from the dynamic exercise. Occlusion of the circulation of the quadriceps completely abolished the resynthesis of PC. Restoration of resynthesis occurred only after release of occlusion.

Adenosine Triphosphate↗

Lactate content and pH in muscle obtained after dynamic exercise.

Analyzes were made on muscle samples taken from the lateral part of the m. quadriceps femoris of man (lactate, pyruvate, and pH) on venous blood (lactate, pyruvate) and on capillary blood (pH). Samples were taken at rest, immediately after termination of dynamic exercise and during 20 min recovery from exhaustive dynamic exercise. Muscle pH decreases from 7.08 atrest to 6.60 at exhaustion. Decrease in muscle pH was linearly related to muscle content of lactate + pyruvate. The relationship was slightly different from what has been obtained after isometric exercise and this difference was ascribed to acid-base exchange with the blood during dynamic exercise. Lactate content was highly elevated in muscle after exercise and the concentration was 2-3 times higher than in blood. Pyruvate content was, however, only slightly higher than that at rest. During recovery, lactate content of muscle decreased exponentially with respect to time, whereas pyruvate content increased. The half-time of lactate decrease was 9.5 min. From the lactate dehydrogenase equilibrium relative values on NADH/NAD ratio could be calculated. It was found that NADH/NAD was highly increased after exercise and that it had not returned to the basal value after 20 min recovery.

Adult↗

Influence of severe potassium depletion and subsequent repletion with potassium on muscle electrolytes, metabolites and amino acids in man.

1. Two women with severe hypokalaemic alkalosis were investigated by means of muscle biopsy before and at the end of 2 and 3 weeks respectively of intense therapy with potassium chloride. 2. The muscle biopsy material was analysed for water, electrolytes, adenine nucleotides, phosphocreatine, free creatine, pyruvate, lactate, glycogen and free amino acids. The extra- and intra-cellular distribution of water, electrolytes and amino acids was calculated by the chloride method. 3. Both patients showed a marked loss of intracellular potassium and an increase in intracellular sodium concentration. The muscle magnesium content was also slightly decreased. After repletion with potassium chloride, muscle sodium and potassium became normal. 4. The contents of creatine phosphate, ATP, ADP, AMP, lactate and pyruvate were within normal limits, but the phosphocreatine/total creatine ratio was reduced. After repletion, a small change in the apparent creatine-phosphokinase equilibrium had occurred, suggesting a minor increase in intracellular pH. 5. The concentrations of the basic amino acids, lysine, arginine and ornithine were increased far above normal. The intracellular accumulation of arginine was much higher than the increase in lysine concentration and histidine concentration was normal. This differs from findings in potassium-depleted rats, where the intracellular lysine concentration is much higher than arginine concentration and histidine is high as well. After potassium repletion the intracellular concentration of ornithine, lysine and arginine became normal in one case and decreased considerable in the other. An increased intracellular concentration of glutamate and glutamine was also observed after potassium repletion.

Acidosis↗