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Biomedical subjects

E Hultman

Publications and source records attributed to E Hultman.

At least 109 records · Page 6Linked to original sources

Muscle alkali-soluble protein, carnitine, water and electrolytes in patients with persistent post-operative infection.

The muscle contents of water, electrolytes, creatine, alkali-soluble protein (ASP) and carnitine were determined using percutaneous muscle biopsy technique. Seven patients with prolonged catabolic states and subsequent respiratory failure were studied. Twelve age- and sex-matched healthy subjects were used for comparison. The muscle content of alkali-soluble protein in relation to the content of DNA was less than half of control values, indicating a loss of more than 50% of muscle protein content. The muscle carnitine content was 25.9 +/- 6.5 mumol/g alkali-soluble protein, suggesting a preserved muscle carnitine concentration. Total muscle water was increased by over 20%, mainly due to an increase in extracellular water. Muscle sodium and chloride contents were doubled. The content of magnesium was slightly reduced but muscle potassium was normal. The marked depletion of muscle protein may have contributed to the requirements for artificial ventilation and the difficulties in weaning off the ventilator. The increase in muscle water masks the loss of metabolically active muscle tissue yielding low values for energy expenditure when relating to body weight. The benefit of the use of the ASP/DNA ratio in nutritional assessment is emphasised.

Journal Article↗

Regulation of glycogenolysis in human skeletal muscle.

The role of inorganic phosphate on the regulation of glycogenolysis in resting and contracting muscle was studied in human quadriceps muscle. Increased Pi content was achieved by intermittent electrical stimulation of the muscle followed by occlusion of the blood flow. Occlusion resulted in the maintenance of a high Pi content over a 60-s observation period during which the muscle was either at rest or was stimulated electrically. The study was performed with and without infusion of epinephrine (EPI). In the absence of EPI the phosphorylase a fraction was 50% immediately at the end of the initial stimulation period, declining to 22% after 60 s. With EPI corresponding values for phosphorylase a were 91% initially, 56% after 30 s, and 33% after 60 s, respectively. In both cases the Pi content was increased by approximately 35 mmol/kg dry muscle during the stimulation and remained constant during the occlusion. In neither of these situations was significant degradation of glycogen observed during the occlusion. In the study performed with electrical stimulation during the occlusion period, muscle glycogen degradation was observed both with and without EPI. Phosphorylase a fractions and Pi contents in this study were similar to those observed when muscle was rested over the 60-s occlusion period. The paradox of a high Pi content and extensive transformation of phosphorylase to the a form but low glycogenolytic activity points to additional factors in the regulation of glycogen breakdown.

Adenosine Triphosphate↗

Glycogen degradation during isometric exercise at low contraction force.

The glycogen content was measured in biopsy sample of human vastus lateralis muscle during prolonged isometric contraction with low force generation. In the first experiment 15% of the maximum voluntary contraction force (MVC) was held for 10 min. Glycogen utilization was 68.1 mmol glucosyl units.kg-1 dry muscle (d.m.). The study was continued by intermittent contractions of 50 s duration and 10 s rest repeated for 50 min. This resulted in a total glycogen utilization of 167.5 mmol glycosyl units.kg-1 d.m. The study was repeated with a force set of 7.5% MVC starting with 20 min continuous contraction followed by the same intermittent contractions for a further 100 min. The glycogen decrease was 15 mmol after the continuous contraction and totally 50 mmol after 2 h with the lower force. Thus the glycogen degradation rate even at low contraction force was related to the force level, being 6 times higher when the force was increased from 7.5 to 15% MVC. With prolonged isometric work periods at work loads corresponding to 15% MVC or higher depletion of the glycogen store can limit work performance capacity.

Adult↗

Phosphorylase activity in needle biopsy samples--factors influencing transformation.

Phosphorylase was determined in biopsy samples frozen immediately or after a delay of 10 s to 6 min. Muscle biopsies were performed at rest without and with propranolol, or adrenalin infusion and after electrical stimulation. The phosphorylase a fraction was 36% (28-44) in resting samples frozen immediately and 12% (12-13) after 10 s delay and remained at the same level when the freezing was further delayed (up to 6 min). It is suggested that an increase in [Ca2+] in the cytoplasm due to the insertion of the needle in muscle or cutting of tissue membranes may cause transformation of phosphorylase from b to a form, a transformation which is restored when Ca2+ is pumped back during the delay. Also the increased phosphorylase a fraction observed in biopsy samples obtained during adrenalin infusion reverted partially back when freezing was delayed for 10 s and 30 s, respectively. In muscle samples taken during contraction the mole fraction of phosphorylase a decreased from 53 to 12% when freezing was delayed for 10 s. The lowest value of the phosphorylase a mole fraction was observed in resting muscle after beta-blockade when the tissue samples were frozen 10 s after sampling and corresponded to 10% of the total phosphorylase. It is concluded that both muscle sampling and circulating adrenalin will increase phosphorylase a fraction in resting muscle and probably also augment the effect of adrenalin infusion.

Adult↗

Skeletal muscle glucolysis, glycogenolysis and glycogen phosphorylase during electrical stimulation in man.

Phosphorylase activity, glycogenolytic and glucolytic rates were estimated in human quadriceps muscle during electrical stimulation at 20 Hz. Two stimulation periods of 10 s duration were separated by a pause of 60 s. The blood circulation to the leg was intact or occluded during the experiment. ATP turnover rates and force production were of the same order during the two contraction periods both with and without intact blood flow. Also the increase in phosphorylase a activity (from approximately 30% to approximately 65%) was the same during the contraction periods. Glycogenolytic and glucolytic rates were however about 30% higher (P less than 0.05) during the second contraction compared with the first when circulation was occluded, but similar when the circulation was intact. During the 60 s rest period, the phosphocreatine (PCr) was maintained at a low level and inorganic phosphate (Pi) remained increased under occluded circulation while PCr was resynthesized in the rest period with intact circulation. We conclude that the increased glycogenolytic rate observed during the second contraction with occluded blood circulation was due to the high [Pi] in the muscle and that the increased glucolytic rate was caused by high [Pi] and low [PCr]. In the rest period with anoxia the glycogenolysis was completely inhibited and glucolysis was inhibited by 95% in spite of the changes in [PCr] and [Pi].

Adult↗

Energy cost and metabolic regulation during intermittent and continuous tetanic contractions in human skeletal muscle.

Muscle ATP turnover, glycogenolytic, and glycolytic rates were estimated to compare the energy cost and glycolytic regulation of 102.4 s of continuous and intermittent stimulation. Quadriceps femoris muscles of male subjects were stimulated at 20 Hz for one continuous contraction (n = 6) or a series of 64 contractions (1.6 s on, 1.6 s off; n = 6). Leg blood flow was occluded and muscle biopsies were obtained at rest and following 51.2 and 102.4 s of contraction time in both conditions. Isometric force production by the activated knee extensors decreased to 55% of initial contraction force with intermittent and 80% of initial contraction force with continuous stimulation following 51.2 s of contraction time. Corresponding ATP turnover rates were 4.49 +/- 0.39 and 3.80 +/- 0.44 mmol.kg dry muscle-1.s-1. When normalized for tension production the respective energy costs of intermittent and continuous contractions were 3.66 +/- 0.47 and 2.64 +/- 0.36 mmol ATP.kg-1.100 N-1. Glycogenolytic rates were identical during the first 51.2 s of stimulation but glycolysis was higher in the intermittent group (1.05 +/- 0.10 vs. 0.86 +/- 0.11 mmol.kg-1.s-1). We suggest that the increased ATP utilization of intermittent contractions is associated with enhanced Ca2+-transport ATPase activity during relaxation and enhanced actomyosin ATPase activity during the early portion of each contraction. Glycolytic rate is dependent on ATP demand and regulated by allosteric modulators of phosphofructokinase and pyruvate kinase which are released or consumed in the reactions associated with contraction.

Adenosine Diphosphate↗

Epinephrine infusion enhances muscle glycogenolysis during prolonged electrical stimulation.

To determine the effects of epinephrine (EPI) infusion on muscle glycogenolysis and force production, the quadriceps muscles of both legs in six subjects were intermittently stimulated for 30 min. Contractions lasted 1.6 s (20 Hz) and were separated by 1.6 s of rest. EPI was infused (approximately 0.14 micrograms.kg body wt-1.min-1) in one leg during the last 15 min and the vastus lateralis was biopsied at rest (control leg only) and after 15, 18 (EPI leg only), and 30 min of stimulation. EPI infusion doubled the mole fraction of phosphorylase a (22.5 +/- 4.1 to 44.8 +/- 9.0%) and glycogenolysis (2.16 +/- 0.72 to 5.45 +/- 0.81 mmol glucosyl U.kg dry muscle wt-1.min-1) during stimulation. Muscle glucose 6-phosphate increased from 3.04 +/- 0.17 to 6.43 +/- 0.20 mmol/kg dry muscle wt, and lactate increased from 25.8 +/- 4.4 to 34.3 +/- 4.6 mmol/kg after 3 min of EPI infusion. Isometric force production was unaltered by EPI infusion. These results demonstrate a strong glycogenolytic effect of EPI infusion during prolonged electrical stimulation and suggest that the extra pyruvate formed was converted mainly to lactate. Exclusive anaerobic metabolism of the extra substrate would provide only a 10% increase in total ATP production, possibly accounting for the lack of improvement in force production. We suggest that the decrease in force production during prolonged electrical stimulation is related to decreased excitation of the contractile mechanism rather than inhibition of cross-bridge turnover caused by a shortage of energy or accumulation of hyproducts.

Adenosine Triphosphate↗

Energy cost and fatigue during intermittent electrical stimulation of human skeletal muscle.

Force generation and ATP utilization under anaerobic conditions were studied in the quadriceps femoris muscle of six volunteers. Electrical stimulation (20 Hz) was used to produce contractions with a duration of 0.8 s in one leg and contractions with a duration of 3.2 s in the other leg. The two procedures were designed to give the same total contraction time of 51 s and used the same number of stimulation pulses. Muscle biopsies were taken at rest and after 22 and 51 s of work and analyzed for ATP, phosphocreatine, and glucolytic intermediates. The results were compared with previous studies on continuous and intermittent stimulation. Fatigue developed significantly faster with contractions of short duration, and the energy cost was higher. Since force at the end of stimulation had a negative correlation to ATP utilization, there is no indication that the energy resources limit force generation. By comparison of stimulations producing the same amount of isometric work but with a different number of contractions, we estimate that the energy cost for activation and relaxation of a 1-s contraction is approximately 37% of the total ATP consumption.

Adenosine Diphosphate↗

Experimental meningitis in the rabbit. II. Cerebral energy metabolism in relation to increased cerebrospinal fluid concentrations of lactate.

We have analyzed cerebral energy metabolism in rabbits with Streptococcus pneumoniae or Escherichia coli meningitis aiming at an increased understanding of the cerebrospinal fluid (CSF) lactacidosis observed in this disease. After intracisternal inoculation of bacteria the lactate concentration in the CSF increased to 9.7 +/- 0.7 (mean +/- SE) mmol/l compared to control values of 3.2 +/- 0.2 mmol/l. Simultaneously sampled brain tissue from parietal cortex, caudate nucleus, and thalamus showed no increase in lactate concentrations. The high-energy phosphate content decreased only marginally, phosphocreatine levels by 11-17% in the cortex and in the caudate nucleus, and adenosine triphosphate concentrations by 15%, but only in the caudate nucleus. Our results indicate that the CSF lactate increase in bacterial meningitis is not primarily linked to cerebral lactacidosis. The decreased concentrations of high-energy phosphates in diseased animals need further study but may be due to increased intracranial pressure and reduced capillary blood flow.

Animals↗

Anaerobic energy release in skeletal muscle during electrical stimulation in men.

The quadriceps femoris muscles of seven men were electrically stimulated under extended anaerobic conditions to quantitate anaerobic energy release and the contribution of the glycolytic system to total ATP production. Muscles were intermittently stimulated 64 times at 20 Hz while leg blood flow was occluded. Each contraction lasted 1.6 s and was followed by 1.6 s of rest. The total contraction time was 102.4 s. Muscle biopsies were taken at rest and following 16, 32, 48, and 64 contractions. The ATP turnover rates during the four 16-contraction periods were 6.12, 2.56, 2.17, and 0.64 mmol X kg dry muscle-1 X s-1 contraction time. Glycolysis provided 58%, phosphocreatine 40% and a decreased ATP store 2% of the consumed energy during the initial 16 contractions. Glycolysis was responsible for 90% of the total ATP production beyond contraction 16. Absolute glycolytic ATP production decreased to 60, 55, and 17% of the amount in the initial 16 contractions during the final three periods, respectively. In conclusion glycolysis produced approximately 195 mmol ATP/kg dry muscle during the initial 48 contractions (76.8 s) and only approximately 15 mmol ATP/kg dry muscle during the final 16 contractions. Equivalent values for total ATP turnover were 278 and 16.5 mmol/kg dry muscle.

Adenosine Diphosphate↗

Skeletal muscle glycogenolysis, glycolysis, and pH during electrical stimulation in men.

Glycogenolytic and glycolytic rates were estimated and muscle pH (pHm) was measured in electrically stimulated quadriceps femoris muscles of seven men. Leg blood flow was occluded and muscles were stimulated 64 times at 20 Hz, with contractions lasting 1.6 s and separated by pauses of 1.6 s. Muscle biopsies were obtained at rest and following 16, 32, 48, and 64 contractions. Glycolytic intermediates and several modulators of the glycolytic enzyme phosphofructokinase (PFK) were measured. Glycogenolytic and glycolytic rates were 1.68 and 1.26 mmol glucosyl units X kg dry muscle-1 X S-1 contraction time during the initial 16 contractions and pHm decreased from 7.00 +/- 0.01 to 6.70 +/- 0.03. During the subsequent 32 contractions both glycogenolytic and glycolytic rates were maintained at approximately 0.70 mmol X kg-1 X S-1 and pHm decreased to 6.45 +/- 0.04. In the final 16 contractions, both rates were very low and pHm was unchanged. Therefore, PFK remained active despite increasing acidity until pHm decreased to approximately 6.45. We conclude that increases in the concentrations of several positive modulators partially reverses pH-dependent ATP inhibition of PFK in vivo, permitting glycolytic activity to continue in the pHm range of 6.70-6.45.

Adult↗

ATP utilization and force during intermittent and continuous muscle contractions.

Energy utilization and force generation under anaerobic conditions were studied in electrically stimulated quadriceps femoris muscle of four volunteers. To investigate the effects of intermittent vs. continuous stimulation one leg was stimulated intermittently and the other continuously during 50 s. The same initial force was produced, and biopsy samples were obtained before the stimulation and after 10, 20, and 50 s and analyzed for energy-rich phosphagens, glycolytic intermediates, and phosphorylase. The ATP utilization and glycolysis were greater during intermittent contraction, but glycogenolysis was equal. ATP content decreased to lower values after intermittent contraction (16.4 compared with 19.6 mmol/kg dry muscle after continuous contraction). Force generation was well preserved during continuous contraction but successively decreased after 20 s of intermittent stimulation down to 50% of initial at end of work. The energy cost per unit work was greater during intermittent stimulation and increased with contraction time, whereas it decreased with time during continuous stimulation. The decrease in force generation in intermittent exercise is suggested to be due to the higher energy cost for contraction resulting in greater changes in the intracellular environment with lower ATP and increased H+ and Pi. These changes would decrease both activation of the contractile system and the cross-bridge turnover rate resulting from activation.

Adenosine Diphosphate↗

Acetylcarnitine formation during intense muscular contraction in humans.

To study the changes in carnitine during intense muscular effort subjects underwent 4 min intermittent electrical stimulation of the quadriceps femoris muscle and on a separate occasion performed 4 min exercise on a bicycle ergometer. Biopsies of the vastus lateralis muscle were taken at rest and after 2 and 4 min of stimulation or exercise. Resting mean muscle total carnitine content was 20.0 mmol/kg dry muscle. Approximately 77% was free carnitine and 19% acetylcarnitine. Four minutes of stimulation or intense exercise did not effect total carnitine but did result in a marked fall in free carnitine and almost equivalent rise in acetylcarnitine. The results indicate that acetylcarnitine is a major metabolite formed during intense muscular effort and that carnitine may function in the regulation of the acetyl-CoA/CoA ratio by buffering excess production of acetyl units.

Acetylcarnitine↗

Experimental bacterial meningitis in the rabbit: cerebrospinal fluid changes and its relation to leukocyte response.

This study was focused on cerebrospinal fluid (CSF) manifestations in experimental Streptococcus pneumoniae and Escherichia coli meningitis in rabbits. An increased (p less than 0.001) CSF lactate concentration was found in infected animals, mostly not accompanied by a decrease in CSF glucose concentrations. Despite a marked difference in CSF cellular response between the 2 etiological groups no significant difference in CSF lactate levels was found. Neither did CSF lactate levels correlate to CSF polymorphonuclear cell counts. CSF concentrations of albumin were with large variations above control levels in all infected animals. Also a small or moderate increase in CSF albumin levels was generally associated with a marked increase in CSF lactate concentration. The concentration of total amino acids in the CSF was above control values (mean + 2 SD) in 9/21 infected animals. Halothane/N2O anesthesia for 25 min increased (p less than 0.05) CSF levels of glucose, partly independent of alterations in plasma glucose concentrations, in both infected rabbits and in controls.

Amino Acids↗

Patient-related factors influencing the plasma acetate concentration during haemodialysis.

In 44 adult patients, 16 men and 28 women, with chronic renal failure who were dialysed under uniform conditions (Dialyser area 1.2 m2, blood flow 200 ml/min, dialysate flow 500 ml/min, dialysis fluid acetate concentration 35 mmol/l) we determined the plasma acetate concentration after 1 h of haemodialysis (1H-Ac) and 3 h of dialysis (3H-Ac). 1H-Ac was significantly lower than 3H-Ac in both male and female patients, and both mean values were significantly greater in males than in females. 3H-Ac showed a negative correlation with body surface area, serum creatinine before dialysis, and serum albumin, respectively. Using multivariate analysis, body surface area and serum creatinine showed the strongest significant combination of independent variables (R = 0.66), and accounted for 43% of the total variance in 3H-Ac. Sex, age, serum albumin and haematocrit did not further contribute to explaining the variance in 3H-Ac independently of body surface area and serum creatinine. Assuming that serum creatinine to some extent reflects the generation rate of creatinine and thus the muscle mass of the patients, our findings suggest that the rate of metabolism of acetate is proportional to the body size and that acetate is metabolised to a large extent in skeletal muscle. Accordingly, malnutrition with muscle-wasting may lead to slow metabolism of acetate and possibly to exaggerated acetate-related side-effects.

Acetates↗

Muscle water and electrolytes in patients undergoing continuous ambulatory peritoneal dialysis.

Muscle water and electrolytes were determined in percutaneous muscle biopsy material from m. quadriceps femoris in 33 uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for 1-38 months, and in 34 normal subjects. The patients showed increased muscle contents of water, sodium, and chloride relative to fat-free solids (FFS); both intra- and extracellular water contents were increased. The total water content was inversely correlated with the duration of CAPD. The muscle potassium content was increased, both relative to FFS and to magnesium, whereas the intracellular potassium concentration was normal. Despite hypermagnesemia, the muscle content of magnesium was normal and the intracellular concentration was even slightly decreased due to the increase in intracellular water. We conclude that muscle water and electrolyte status is abnormal in CAPD patients, but the alterations appear to be less marked than in uremic patients undergoing other forms of therapy.

Adult↗

Relaxation time during intermittent isometric contraction in subjects with different capacity for oxidative work.

Force and relaxation time were measured during intermittent electrical stimulation of the quadriceps muscle on 14 volunteers. Each stimulation had a duration of 1.6 s and the work to rest ratio was 1:1. Relaxation times increased during the first 20-30 contractions and then reached a plateau. The rate of increase in relaxation time during the first contractions as well as the plateau levels were found to correlate to maximal oxygen uptake capacity, predicted from submaximal cycle ergometer tests. Since slow-twitch fibres are known to produce work at a lower energy cost it is suggested that studies of relaxation time changes could provide functional estimates of fibre-type proportions in the quadriceps muscle.

Adult↗