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Biomedical subjects

E Hultman

Publications and source records attributed to E Hultman.

At least 73 records · Page 4Linked to original sources
PubMed1992

Caffeine ingestion and muscle metabolism during prolonged exercise in humans.

We examined the effects of a high-caffeine dose on endurance performance and muscle acetyl group metabolism during prolonged exercise. Eight subjects cycled to exhaustion at approximately 80% maximal oxygen uptake (VO2max) 1 h after ingestion of 9 mg/kg body wt dextrose (Pl) or caffeine (Caf). In the Pl trial, muscle biopsies were taken at rest (1 h postingestion) and at 15 min and exhaustion during exercise. The Caf trial followed the same protocol 1 wk later, with an additional biopsy at the time corresponding to Pl exhaustion. The subjects cycled significantly longer during the Caf trial (96.2 +/- 8.8 min) than in the Pl trial (75.8 +/- 4.8 min). Net glycogenolysis during the initial 15 min of cycling was reduced in the Caf vs. Pl trial (4.7 +/- 1.5 vs. 10.6 +/- 1.3 mmol.kg dry muscle-1.min-1; P less than 0.05). Muscle citrate concentration was increased at rest with Caf (0.59 +/- 0.07 vs. 0.37 +/- 0.05 mmol/kg dry muscle; P less than 0.05) but increased to similar values in both trials during cycling. Caf elevated the acetyl-CoA/CoA-SH ratio at rest (0.316 +/- 0.046 vs. 0.201 +/- 0.023; P less than 0.05) but had no effect on the increases in muscle acetyl-CoA and acetylcarnitine during exercise. The results indicate that Caf before exercise decreased muscle glycogenolysis by approximately 55% over the first 15 min of exercise at approximately 80% VO2max. This "spared glycogen" was available late in exercise and coincided with a prolonged time to exhaustion. Increased utilization of intramuscular triacylglycerol and/or extramuscular free fatty acids after caffeine ingestion may inhibit carbohydrate use at rest and early during exercise via elevations in muscle citrate and the acetyl-CoA/CoA-SH ratio. Muscle acetyl-CoA and acetylcarnitine were maintained above resting contents even at exhaustion when muscle glycogen was depleted.

Acetyl Coenzyme A↗
PubMed1992

Adaptation of mitochondrial ATP production in human skeletal muscle to endurance training and detraining.

The adaptation of mitochondrial ATP production rate (MAPR) to training and detraining was evaluated in nine healthy men. Muscle samples (approximately 60 mg) were obtained before and after 6 wk of endurance training and after 3 wk of detraining. MAPR was measured in isolated mitochondria by a bioluminometric method. In addition, the activities of mitochondrial and glycolytic enzymes were determined in skeletal muscle. In response to training, MAPR increased by 70%, with a substrate combination of pyruvate + palmitoyl-L-carnitine + alpha-ketoglutarate + malate, by 50% with only pyruvate + malate, and by 92% with palmitoyl-L-carnitine + malate. With detraining MAPR decreased by 12-28% from the posttraining rate (although not significantly for all substrates). No differences were found when MAPR was related to the protein content in the mitochondrial fraction. The largest increase in mitochondrial enzyme activities induced by training was observed for cytochrome-c oxidase (78%), whereas succinate cytochrome c reductase showed only an 18% increase. The activity of citrate synthase increased by 40% and of glutamate dehydrogenase by 45%. Corresponding changes in maximal O2 uptake were a 9.6% increase by training and a 6.0% reversion after detraining. In conclusion, both MAPR and mitochondrial enzyme activities are shown to increase with endurance training and to decrease with detraining.

Adenosine Triphosphate↗
PubMed1992

PDC activity and acetyl group accumulation in skeletal muscle during prolonged exercise.

Seven subjects cycled to exhaustion [58 +/- 7 (SE) min] at approximately 75% of their maximal oxygen uptake (VO2max). Needle biopsy samples were taken from the quadriceps femoris muscle at rest, after 3, 10, and 40 min of exercise, at exhaustion, and after 10 min of recovery. After 3 min of exercise, a nearly complete transformation of the pyruvate dehydrogenase complex (PDC) into active form had occurred and was maintained throughout the exercise period. The total in vitro activated PDC was unchanged during exercise. The muscle concentration of acetyl-CoA increased from a resting value of 8.4 +/- 1.0 to 31.6 +/- 3.3 mumol/kg dry wt at exhaustion and that of acetylcarnitine from 2.9 +/- 0.7 to 15.6 +/- 1.6 mmol/kg dry wt. This was accompanied by corresponding decreases in reduced CoA (CoASH) from 45.3 +/- 3.1 to 25.9 +/- 3.1 mumol/kg dry wt and in free carnitine from 18.8 +/- 0.7 to 5.7 +/- 0.5 mmol/kg dry wt. Acetyl group accumulation, in the form of acetyl-CoA and acetylcarnitine, was maintained throughout exercise to exhaustion while the glycogen content decreased by 90%. This suggests that availability of acetyl groups was not limiting to exercise performance despite the nearly total depletion of the glycogen store. The increased acetyl-CoA-to-CoASH ratio during exercise caused inhibition of neither the PDC transformation nor the calculated catalytic activity of active PDC.

Acetyl Coenzyme A↗
PubMed1992

Binding of dietary cobalt to sarcoplasmic reticulum proteins.

It has previously been shown that cobalt accumulates in the myocardium of rats, mainly the sarcoplasmic reticulum (SR) and the mitochondrial inner membrane. In order to investigate the mode of accumulation of cobalt in the SR, rats were given a dietary cobalt supplementation of 40 mg of CoSO4 x 7H2O kg-1 body wt, after which the rats were sacrificed and the sarcoplasmic reticulum was isolated. The SR proteins were subjected to analysis by polyacrylamide gel electrophoresis followed by protein staining and determination of the content of cobalt in each protein band. The major cobalt-binding protein was found to have a molecular weight of about 100,000; a 200,000 molecular weight protein was also found to bind cobalt, although less extensively. These results suggest that cobalt is bound to the monomeric and dimeric forms of Ca(2+)-ATPase in the SR of the myocardium.

Animals↗
PubMed1991

A sensitive radioisotopic assay of pyruvate dehydrogenase complex in human muscle tissue.

A radioactive assay for the determination of pyruvate dehydrogenase complex activity in muscle tissue has been developed. The assay measures the rate of acetyl-CoA formation from pyruvate in a reaction mixture containing NAD+ and CoASH. The acetyl-CoA is determined as [14C]citrate after condensation with [14C]-oxaloacetate by citrate synthase. The method is specific and sensitive to the picomole range of acetyl-CoA formed. In eleven normal subjects, the active form of pyruvate dehydrogenase (PDCa) in resting human skeletal muscle samples obtained using the needle biopsy technique was 0.44 +/- 0.16 (SD) mumol acetyl-CoA.min-1.g-1 wet wt. Total pyruvate dehydrogenase complex (PDCt) activity was determined after activation by pretreating the muscle homogenate with Ca2+, Mg2+, dichloroacetate, glucose, and hexokinase. The mean value for PDCt was 1.69 +/- 0.32 mumol acetyl-CoA.min-1.g-1 wet wt, n = 11. The precision of the method was determined by analyzing 4-5 samples of the same muscle piece. The coefficient of variation for PDCa was 8% and for PDCt 5%.

Acetyl Coenzyme A↗
PubMed1991

Regional fibrinolysis following total hip replacement.

The local effect of operative trauma on the fibrinolytic system was studied in ten patients undergoing total hip replacement. Catheters were inserted in the femoral veins on both sides and blood was sampled from these catheters perioperatively. The following fibrinolytic variables were analysed in plasma and related to the different steps of surgery: tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI-1) activity. During surgery PAI-1 activity and t-PA antigen in the operated limb were significantly increased compared with preoperative values. There was a significant difference in PAI-1 activity and t-PA antigen between the operated and the non-operated limbs during surgery and within one hour postoperatively. During fixation of the femoral implant there was a significant difference between the operated and the non-operated limbs in t-PA activity. Thus the regional fibrinolytic response to trauma was dissociated from the response in the non-operated limb. The clinical relevance of the observed alterations in regional fibrinolysis, as related to thrombogenic mechanisms after hip surgery, remains to be elucidated.

Aged↗
PubMed1991

Relaxation and force during fatigue and recovery of the human quadriceps muscle: relations to metabolite changes.

Force and relaxation were measured during electrical stimulation of the quadriceps muscle of 14 volunteers. Stimulation produced 51.2 s of intermittent ischaemic contractions either as 16 3.2-s tetani or as 64 0.8-s tetani. Changes during recovery were followed for 180 s. On 8 subjects muscle biopsies were taken during work and after the rest period for determination of ATP, phosphocreatine and intermediates in glucolysis. The stimulation using 0.8-s contractions gave more pronounced fatigue and slowing of relaxation. There was a good correlation between force and relaxation during work but this relation changed during recovery, indicating that no general relation exists between these two contraction characteristics. In the 0.8-s stimulation more ATP was utilized and there were more profound changes in metabolite levels. We found a correlation between estimated [H2PO4-] and relaxation covering both work and recovery and hypothesize that inorganic phosphate and its removal by phosphocreatine resynthesis during recovery might be important. Since stimulation patterns differ in force and relaxation even after the recovery period we suggest that additional factors, such as pH, are of importance in this work model.

Adenosine Triphosphate↗
PubMed1991

Muscle composition in relation to age and sex.

1. A method is described enabling the determination of fat, water, electrolytes, protein, DNA, RNA and total creatine in a single sample of human muscle obtained by the percutaneous needle-biopsy technique. The amino acid content can also be analysed in the same muscle sample. 2. Fifty healthy subjects were studied: 29 between 19 and 40 years of age, 11 between 41 and 60 years of age, and 10 between 61 and 85 years of age. The two groups aged less than 60 years showed only marginal differences in muscle composition, whereas the highest age group showed increases in muscle fat content in relation to tissue weight and decreases in alkali-soluble protein content in relation to both tissue weight and tissue DNA content. Also, potassium, magnesium, total creatine and RNA contents were decreased in this age group when related to tissue DNA content. When alkali-soluble protein was used as a reference base, only magnesium content was decreased. 3. A comparison was also made between female (n = 23) and male (n = 18) subjects in the age groups below 60 years. Differences observed included a higher fat content in female muscle, and an increase in total creatine content in relation to tissue weight. The alkalisoluble protein content was lower per muscle cell in the females when calculated on the basis of DNA content. 4. The results show that in the assessment of muscle constituents, age and sex must be taken into account.

Adult↗
PubMed1991

ATP production in isolated muscle mitochondria from haemodialysis patients: effects of correction of anaemia with erythropoietin.

1. The ATP production rate in isolated skeletal muscle mitochondria was measured with a bioluminescence method, before and during erythropoietin treatment, in 21 anaemic haemodialysis patients. In addition, the concentrations of ATP, phosphocreatine and total creatine and the ratio of alkali-soluble protein to DNA were determined in skeletal muscle. Maximal oxygen uptake and maximal exercise capacity were determined on a bicycle ergometer. 2. The results unexpectedly showed a 35% higher mitochondrial ATP production rate in the patients before erythropoietin treatment than in sedentary control subjects. On the other hand, mitochondrial density, as measured by the activity of the matrix enzyme glutamate dehydrogenase, was the same in the patients as in the sedentary control group. After 1 year on maintenance erythropoietin treatment, the ATP production rate per kg of muscle decreased in five out of seven patients and reached the same level as in the sedentary control subjects. The ratio between ATP production rate and glutamate dehydrogenase activity was on average 40% higher in the patients at the start and decreased towards the control level in six out of seven patients after 1 year on maintenance erythropoietin treatment. When related to the mitochondrial protein content, a significant reduction in the ATP production rate was observed. 3. The ratio of alkali-soluble protein to DNA in skeletal muscle and the concentrations of ATP, phosphocreatine and total creatine in skeletal muscle at rest were normal in the patients and did not change during the study. The maximal aerobic power improved by 25% after the correction of anaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Long-term, open catheterization of the spinal subarachnoid space for continuous infusion of narcotic and bupivacaine in patients with "refractory" cancer pain. A technique of catheterization and its problems and complications.

The technique of long-term, open catheterization of the spinal subarachnoid space for infusion of analgesics in patients with refractory cancer pain is sparsely reported in the literature. We report on a technique using 18G Portex nylon catheters and 16G-17G Tuohy needles, and its problems and complications. One hundred fifty-seven catheters were inserted in 142 patients, in most of them (79%) under deep sedation and local anesthesia. Attempts were made to place the catheter tip as close to the painful segments as possible. The catheters were tunneled subcutaneously (87% of them paravertebrally, over the shoulder, and further parasternally to the third chondrocostal cartilage). The Luer connections of the catheters were fixed to the patients' skin with monofilament steel sutures of dimension 0 and connected to a bacterial filter. At the end of the procedure, 10 ml isotonic saline was injected intrathecally to prevent postspinal puncture headache. Absorbent and impermeable dressings were applied over the tunnel exit, catheter Luer connection and bacterial filter. Antibiotics were given on the day of insertion and 2 days thereafter. During the insertion procedure, the following problems and complications were encountered; two or more attempts before successful spinal-dural puncture (32%), accidental puncture of an extradural vessel (10%), difficult dural puncture (18%), absence of free dripping of cerebrospinal fluid (CSF) in spite of successful dural puncture (4%), blood-stained CSF (9%), radicular pain and paresthesiae (4%), difficult advancement of the catheter (6%), difficult tunneling (11%), and bleeding in the tunnel (0.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Long-term intrathecal morphine and bupivacaine in "refractory" cancer pain. I. Results from the first series of 52 patients.

Neither epidural (EDA) or intrathecal (IT) morphine nor EDA opiate + bupivacaine provides acceptable relief of some types of cancer pain, e.g. pain originating from mucocutaneous ulcers, deafferentation pain, continuous and intermittent visceral and ischaemic pain, and that occurring with body movement as a result of a fracture. To improve pain relief in such conditions, we gave combinations of morphine and bupivacaine through open IT-catheters to 52 patients with "refractory", severe (VAS 7-10 out of 10), complex cancer pain (Edmonton Stage-3), for periods of 1-305 (median = 23) days. The efficacy of the treatment was estimated from: 1) daily dosage (intraspinal and total opiates, and intraspinal bupivacaine), and 2) scores of non-opiate analgesic and sedative consumption, gait and daily activities, and amount and pattern of sleep. Forty-four patients obtained continuous and acceptable pain relief (VAS 0-2), 26 of them with daily doses of IT-bupivacaine of less than or equal to 30 mg/day (less than or equal to 1.5 mg/h). Higher IT-bupivacaine doses (greater than 60-305 mg/day), not always giving acceptable pain relief, were necessary in 13 patients with deafferentation pain from the spinal cord or brachial or lumbosacral plexuses or pain from the coeliac plexus, or from large, ulcerated mucocutaneous tumours. By combining IT-bupivacaine with IT-morphine, it was possible to use relatively low IT-morphine doses (10-25 mg/day during the first 2 months of treatment) in more than half of the patients. The IT-treatment significantly decreased the total (all routes) opiate consumption and significantly improved sleep, gait and daily activities. For the whole period of observation (6 months), the IT-treatment was assessed as adequate in 3.8%, good in 23.1%, very good in 59.6% and excellent in 13.5% of the cases. Adverse effects of the IT-bupivacaine (paraesthesiae, paresis, gait impairment, urinary retention, anal sphincter disturbances and orthostatic hypotension) did not occur with doses of 2.5-3.0 mg/h (approx. 60-70 mg/day).

Adult↗
PubMed1991

Decreased renal clearance of sodium in cystic fibrosis.

In 10 patients with cystic fibrosis (CF) and 10 controls of similar age quantitative segmental handling of sodium was estimated by lithium clearance. In the CF group, there was a tendency for an increased glomerular filtration rate (GFR) and increased absolute proximal sodium reabsorption. The fractional distal sodium reabsorption was significantly (p = 0.015) increased and sodium clearance was significantly (p less than 0.01) decreased in CF.

Adult↗
PubMed1991

Acetyl group accumulation and pyruvate dehydrogenase activity in human muscle during incremental exercise.

The changes in the muscle contents of CoASH and carnitine and their acetylated forms, lactate and the active form of pyruvate dehydrogenase complex were studied during incremental dynamic exercise. Eight subjects exercised for 3-4 minutes on a bicycle ergometer at work loads corresponding to 30, 60 and 90% of their VO2max. Muscle samples were obtained by percutaneous needle biopsy technique at rest, at the end of each work period and after 10 minutes of recovery. During the incremental exercise test there was a continuous increase in muscle lactate, from a basal value of 4.5 mmol kg-1 dry weight to 83 mmol kg-1 at the end of the final period. The active form of pyruvate dehydrogenase complex increased from 0.37 mmol acetyl-CoA formed per minute per kilogram wet weight at rest to 0.80 at 30% VO2max, 1.28 and 1.25 at 60 and 90% VO2max, respectively. Both acetyl-CoA and acetylcarnitine increased at the two highest work loads. The increase of acetyl-CoA was from 12.5 mumol kg-1 dry weight at rest to 27.3 after the highest work load and for acetylcarnitine from 6.0 mmol kg-1 dry weight to 15.2. The CoASH and free carnitine contents fell correspondingly. There was a close relationship between acetyl-CoA and acetylcarnitine accumulation in muscle during exercise, with a binding of approximately 500 mol acetyl groups to carnitine for each mole of acetyl-CoA accumulated. The results imply that the carnitine store in muscle functions as a buffer for excess formation of acetyl groups from pyruvate catalyzed by the pyruvate dehydrogenase complex.

Acetyl Coenzyme A↗
PubMed1991

Energy metabolism in single human muscle fibers during contraction without and with epinephrine infusion.

The concentrations of glycogen, ATP, and phosphocreatine were analyzed in types I and II muscle fibers separated from biopsy samples of the quadriceps femoris muscle in five healthy volunteers. Muscle samples were obtained before and after 64 s of intermittent electrical stimulation. The experiment was carried out without and with epinephrine (Epi) infusion. Before stimulation the glycogen concentration was 11% higher in type II than in type I fibers (P less than 0.05). During electrical stimulation, rapid glycogenolysis occurred in type II fibers with hardly any detectable glycogenolysis in type I fibers. The calculated rates of glycogenolysis were 0.18 +/- 0.14 and 3.54 +/- 0.53 mmol glucose.kg dry muscle-1.s-1 in types I and II fibers, respectively. Epi infusion increased the rate of glycogenolysis during electrical stimulation in type I fibers (10-fold) but did not enhance the rate in type II fibers (P greater than 0.05). It is considered that, during short-term maximal muscle contraction, rapid muscle glycogenolysis occurs predominantly in type II fibers even though types I and II fibers are recruited and that, when Epi stimulation of glycogenolysis occurs, this is predominantly limited to type I fibers.

Adenosine Triphosphate↗
PubMed1991

ATP and phosphocreatine changes in single human muscle fibers after intense electrical stimulation.

The recovery pattern of adenine nucleotides and glucolytic intermediates after short-lasting anaerobic exercise was studied. Biopsies were obtained from the vastus lateralis muscle at rest, immediately after intermittent electrical stimulation with occluded circulation (total time 166 s), and after 20 s, 60 s, 5 min, and 15 min of recovery. ATP in single fibers decreased from 23.9 +/- 1.41 to 14.2 +/- 3.20 in type I fibers and from 25.01 +/- 1.20 to 13.1 +/- 2.65 mmol/kg dry muscle in type II fibers postexercise. After 15 min of recovery, ATP was resynthesized to 95 and 76% in type I and type II fibers, respectively. The phosphocreatine (PCr) content in type I fibers at rest was 72.3 +/- 4.50 and 83.3 +/- 9.76 mmol/kg dry muscle in type II fibers. After exercise, PCr was depleted in both fiber types. After the 60 s of recovery the PCr content in type I fibers was significantly higher (P less than 0.05) compared with type II fibers, but, after 5 min of oxidative recovery, the PCr levels were equal in the two fiber types. Fifteen minutes postexercise, type II fibers demonstrated a significantly higher content (97.8 mmol/kg dry muscle) compared with its resting value (P less than 0.05).

Adenosine Triphosphate↗
PubMed1991

Plasma and muscle amino acid and ammonia responses during prolonged exercise in humans.

Plasma and muscle amino acid (AA) and ammonia (NH3) responses were measured during prolonged submaximal exercise in humans. Increased NH3 production during submaximal exercise has been attributed to the activity of the purine nucleotide cycle, without consideration of any possible contribution from AA. Six men cycled at 75% of maximal O2 uptake until exhaustion on two occasions after 2.5 days of ingestion of a high-carbohydrate or mixed diet. Plasma samples (antecubital vein) and muscle biopsies (vastus lateralis) were obtained at rest and during exercise and analyzed for plasma and muscle NH3 and AA as well as muscle metabolites. There were no significant diet effects in these parameters, so the majority of results focus on the effects of exercise. Plasma and muscle NH3 increased significantly from the onset and continued to increase throughout exercise. The total and total essential [AA] of muscle were significantly increased at exhaustion, whereas both the plasma and muscle branched-chain AA contents were unchanged. This suggests that protein catabolism was occurring during exercise and the branched-chain AA were used for energy and NH3 production.

Adult↗