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Biomedical subjects

K Sahlin

Publications and source records attributed to K Sahlin.

At least 73 records · Page 4Linked to original sources
PubMed1989

Adenine nucleotide degradation in human skeletal muscle during prolonged exercise.

Eight healthy men cycled at a work load corresponding to approximately 70% of maximal O2 uptake (VO2max) to fatigue (exercise I). Exercise to fatigue at the same work load was repeated after 75 min of rest (exercise II). Exercise duration averaged 65 and 21 min for exercise I and II, respectively. Muscle (quadriceps femoris) content of glycogen decreased from 492 +/- 27 to 92 +/- 20 (SE) mmol/kg dry wt and from 148 +/- 17 to 56 +/- 17 (SE) mmol/kg dry wt during exercise I and II, respectively. Muscle and blood lactate were only moderately increased during exercise. The total adenine nucleotide pool (TAN = ATP + ADP + AMP) decreased and inosine 5'-monophosphate (IMP) increased in the working muscle during both exercise I (P less than 0.001) and II (P less than 0.01). Muscle content of ammonia (NH3) increased four- and eight-fold during exercise I and II, respectively. The working legs released NH3, and plasma NH3 increased progressively during exercise. The release of NH3 at the end of exercise II was fivefold higher than that at the same time point in exercise I (P less than 0.001, exercise I vs. II). It is concluded that submaximal exercise to fatigue results in a breakdown of the TAN in the working muscle through deamination of AMP to IMP and NH3. The relatively low lactate levels demonstrate that acidosis is not a necessary prerequisite for activation of AMP deaminase. It is suggested that the higher average rate of AMP deamination during exercise II vs. exercise I is due to a relative impairment of ATP resynthesis caused by the low muscle glycogen level.

Adenine Nucleotides↗
PubMed1989

Relationship of contraction capacity to metabolic changes during recovery from a fatiguing contraction.

The relationship between changes in muscle metabolites and the contraction capacity was investigated in humans. Subjects (n = 13) contracted (knee extension) at a target force of 66% of the maximal voluntary contraction force (MVC) to fatigue, and the recovery in MVC and endurance (time to fatigue) were measured. Force recovered rapidly [half-time (t 1/2) less than 15 s] and after 2 min of recovery was not significantly different (P greater than 0.05) from the precontraction value. Endurance recovered more slowly (t 1/2 approximately 1.2 min) and was still significantly depressed after 2 and 4 min of recovery (P less than 0.05). In separate experiments (n = 10) muscle biopsy specimens were taken from the quadriceps femoris muscle before and after two successive contractions to fatigue at 66% of MVC with a recovery period of 2 or 4 min in between. The muscle content of high-energy phosphates and lactate was similar at fatigue after both contractions, whereas glucose 6-phosphate was lower after the second contraction (P less than 0.05). During recovery, muscle lactate decreased and was 74 and 43% of the value at fatigue after an elapsed period of 2 and 4 min, respectively. The decline in H+ due to lactate disappearance is balanced, however, by a release of H+ due to resynthesis of phosphocreatine, and after 2 min of recovery calculated muscle pH was found to remain at a low level similar to that at fatigue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1988

NADH content in type I and type II human muscle fibres after dynamic exercise.

The effect of dynamic exercise on the NADH content of human type I (slow-twitch) and II (fast-twitch) muscle fibres was investigated. Muscle biopsy samples were obtained from the quadriceps femoris of seven healthy subjects at rest and after bicycle exercise at 40, 75 and 100% of the maximal oxygen uptake [VO2(max.)]. At rest and after exercise at 100% VO2(max.), muscle NADH content was significantly higher (P less than 0.05) in type I than in type II fibres. After exercise at 40% VO2(max.), muscle NADH decreased in type I fibres (P less than 0.01), but was not significantly changed in type II fibres. After exercise at 75 and 100% VO2(max.), muscle NADH increased above the value at rest in both type I and II fibres (P less than 0.05). Muscle lactate was unchanged at 40% VO2(max.), but increased 20- and 60-fold after exercise at 75 and 100% VO2(max.) respectively. The finding that NADH decreased only in type I fibres at 40% VO2(max.) supports the idea that type I is the fibre type predominantly recruited during low-intensity exercise. The increase of NADH in both fibre types after exercise at 75% and 100% VO2(max.) suggests that the availability of oxygen relative to the demand is decreased in both fibre types at high exercise intensities.

Humans↗
PubMed1988

Gastrin/CCK-like immunoreactivity in Hatschek's groove of Branchiostoma lanceolatum (Cephalochordata).

Gastrin/CCK-like immunoreactivity was demonstrated in a specific group of epithelial cells in Hatschek's groove. Positive reactions were obtained with antisera directed against the C-terminal amino acid sequence common to mammalian CCK and gastrin, but not with antisera against the midportions of these hormones. No immunoreactivity was obtained with antisera against peptides from hypophysis, neuroendocrine peptides in the gastrointestinal tract, islet hormones, calcitonin, NSE, and S-100. The function of the gastrin/CCK-like peptide found in Hatschek's groove is discussed.

Animals↗
PubMed1988

Oxygen deficit at the onset of submaximal exercise is not due to a delayed oxygen transport.

Six subjects cycled on two occasions for 10 min at power output of 188 +/- 11 W (means +/- SEM), which corresponded to 70 +/- 2% of their maximal oxygen uptake (VO2 max). The exercise intensity was either increased gradually in a stepwise manner over about 15 min (slow transition-S), or increased directly (direct transition-D) to the predetermined power output. Muscle samples from the quadriceps femoris muscle were taken at rest and immediately after exercise in both trials. During exercise with both D and S muscle lactate increased approximately 10 times (P less than 0.01), phosphocreatine decreased about 50% (P less than 0.01) and ADP increased about 20% (P less than 0.05). There were no significant differences between S and D (P greater than 0.05). Furthermore, blood lactate, O2 deficit, O2 debt, and the calculated increase in muscle content of inorganic phosphate (Pi) were all similar between D and S (P greater than 0.05). It is concluded that the O2 deficit and the anaerobic energy utilization is not affected by the rate of transition from rest to exercise. Consequently, the O2 deficit at the onset of exercise is not due to a delay in O2 transport, but may be due to a limited peripheral O2 utilization as a result of metabolic adjustments at the cellular level. Increases in ADP and Pi are suggested to be primary metabolic regulators which activate both aerobic and anaerobic energy production resulting in the O2 deficit.

Adult↗
PubMed1988

Carbohydrate metabolism in human skeletal muscle during exercise is not regulated by G-1,6-P2.

Glucose 1,6-bisphosphate (G-1,6-P2) is a potent activator of phosphofructokinase (PFK) and an inhibitor of hexokinase in vitro. It has been suggested that increases in G-1,6-P2 are a main means by which PFK can achieve significant catalytic function in vivo despite falling pH and that increases in G-1,6-P2 will inhibit hexokinase in vivo. The purpose of the present study was to determine whether contraction-induced changes in flux through PFK and hexokinase are associated with changes in G-1,6-P2 in skeletal muscle. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal O2 uptake (VO2max) and to fatigue [4.8 +/- 0.6 (SE) min] at 100% VO2max. Biopsies were obtained from the quadriceps femoris muscle at rest and after each work load and analyzed for G-1,6-P2. G-1,6-P2 averaged 111 +/- 13 mumol/kg dry wt at rest and 121 +/- 16, 123 +/- 15, and 123 +/- 11 mumol/kg dry wt after the low-, moderate-, and high-intensity exercise bouts, respectively (P less than 0.05 for all means vs. rest). Flux through PFK was estimated to increase exponentially as the exercise intensity increased and muscle pH decreased at the higher work loads, whereas flux through hexokinase was estimated to increase during exercise at 40 and 75% VO2max but decrease sharply at 100% VO2max. These data demonstrate that flux through neither PFK nor hexokinase is mediated by changes in G-1,6-P2 in human skeletal muscle during short-term dynamic exercise.

Adult↗
PubMed1988

Regulation of lactic acid production during exercise.

Lactic acid accumulates in contracting muscle and blood beginning at approximately 50-70% of the maximal O2 uptake, well before the aerobic capacity is fully utilized. The classical explanation has been that part of the muscle is O2 deficient and therefore lactate production is increased to provide supplementary anaerobically derived energy. Currently, however, the predominant view is that lactate production during submaximal dynamic exercise is not O2 dependent. In the present review, data and arguments in support of and against the hypothesis of O2 dependency have been scrutinized. Data underlying the conclusion that lactate production during exercise is not O2 dependent were found to be 1) questionable, or 2) interpretable in an alternative manner. Experiments in human and animal muscles under various conditions demonstrated that the redox state of the muscle is reduced (i.e., NADH is increased) either before or in parallel with increases in muscle lactate. Based on experimental data and theoretical considerations, it is concluded that lactate production during submaximal exercise is O2 dependent. The amount of energy provided through the anaerobic processes during steady-state submaximal exercise is, however, low, and the role of lactate formation as an energy source is of minor importance. It is proposed that the achievement of increased aerobic energy formation under conditions of limiting O2 availability requires increases of ADP, Pi, and NADH and that the increases in ADP (and therefore AMP via the adenylate kinase equilibrium) and Pi will stimulate glycolysis, and the resulting increase in cytosolic NADH will shift the lactate dehydrogenase equilibrium toward increased lactate production.

Animals↗
PubMed1988

Hyperammoniemia during prolonged exercise: an effect of glycogen depletion?

Eight healthy men exercised to exhaustion on a cycle ergometer at a work load of 176 +/- 9 (SE) W corresponding to 67% (range 63-69%) of their maximal O2 uptake (exercise I). Exercise of the same work load was repeated after 75 min of recovery (exercise II). Exercise duration (range) was 65 (50-90) and 21 (14-30) min for exercise I and II, respectively. Femoral venous blood samples were obtained before and during exercise and analyzed for NH3 and lactate. Plasma NH3 was 12 +/- 2 and 19 +/- 6 mumol/l before exercise I and II, respectively and increased during exercise to exhaustion to peak values of 195 +/- 29 (exercise I) and 250 +/- 30 (exercise II) mumol/l, respectively. Plasma NH3 increased faster during exercise II compared with exercise I and at the end of exercise II was threefold higher than the value for the corresponding time of exercise I (P less than 0.001). Blood lactate increased during exercise I and after 20 min of exercise was 3.7 +/- 0.4 mmol/l and remained unchanged until exhaustion. During exercise II blood lactate increased less than during exercise I. It is concluded that long-term exercise to exhaustion results in large increases in plasma NH3 despite relatively low levels of blood lactate. It is suggested that the faster increase in plasma NH3 during exercise II (vs. exercise I) reflects an increased formation in the working muscle that may be caused by low glycogen levels and impairment of the ATP resynthesis.

Adenine Nucleotides↗
PubMed1988

Propranolol enhances adenine nucleotide degradation in human muscle during exercise.

Eight healthy men cycled to exhaustion [4.1 +/- 0.3 (SE) min] during beta-adrenoceptor blockade (beta B) with propranolol. The exercise was repeated on another day with the same power output and duration but without propranolol (control). The total adenine nucleotide (TAN) content in muscle (quadriceps femoris) decreased during exercise, and the decrease was more pronounced during beta B (delta TAN = 4.8 +/- 1.0 mmol/kg dry wt) than during control (delta TAN = 2.8 +/- 0.9; P less than 0.01, beta B vs. control). The decrease in TAN corresponded with a similar increase in inosine 5'-monophosphate (IMP). The increase in IMP was more pronounced during beta B (delta IMP = 5.1 +/- 1.2 mmol/kg dry wt) than during control (delta IMP = 2.8 +/- 0.7; P less than 0.05, beta B vs. control). Similarly, the increase in the content of NH3 in muscle was twice as high during beta B vs. control (P less than 0.01). The increase in muscle lactate and the decrease in phosphocreatine during exercise were similar between treatments, but postexercise hexose phosphates were approximately twofold higher (P less than 0.05) during control than during beta B. It is concluded that beta B enhances the degradation of TAN and the production of NH3 and IMP in muscle during intense exercise. This indicates that the imbalance between the rates of utilization and resynthesis of ATP is more pronounced during beta B possibly because of a decreased O2 transport to the contracting muscle and a diminished activation of glycolysis by the hexose phosphates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1987

Redox state and lactate accumulation in human skeletal muscle during dynamic exercise.

The relationship between the redox state and lactate accumulation in contracting human skeletal muscle was investigated. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal oxygen uptake [VO2(max.)], and to fatigue (4.8 +/- 0.6 min; mean +/- S.E.M.) at 100% VO2(max.). Biopsies from the quadriceps femoris muscle were analysed for NADH, high-energy phosphates and glycolytic intermediates. Muscle NADH was 0.20 +/- 0.02 mmol/kg dry wt. of muscle at rest, and decreased to 0.12 +/- 0.01 (P less than 0.01) after exercise at 40% VO2(max.), but no change occurred in the [lactate]/[pyruvate] ratio. These data, together with previous results on isolated cyanide-poisoned soleus muscle, where NADH increased while [lactate]/[pyruvate] ratio was unchanged [Sahlin & Katz (1986) Biochem. J. 239, 245-248], suggest that the observed changes in muscle NADH occurred within the mitochondria. After exercise at 75 and 100% VO2(max.), muscle NADH increased above the value at rest to 0.27 +/- 0.03 (P less than 0.05) and 0.32 +/- 0.04 (P less than 0.001) mmol/kg respectively. Muscle lactate was unchanged after exercise at 40% VO2(max.), but increased substantially at the higher work loads. At 40% VO2(max.), phosphocreatine decreased by 11% compared with the values at rest, and decreased further at the higher work loads. The decrease in phosphocreatine reflects increased ADP and Pi. It is concluded that muscle NADH decreases during low-intensity exercise, but increases above the value at rest during high-intensity exercise. The increase in muscle NADH is consistent with the hypothesis that the accelerated lactate production during submaximal exercise is due to a limited availability of O2 in the contracting muscle. It is suggested that the increases in NADH, ADP and Pi are metabolic adaptations, which primarily serve to activate the aerobic ATP production, and that the increased anaerobic energy production (phosphocreatine breakdown and lactate formation) is a consequence of these changes.

Adenine Nucleotides↗
PubMed1987

Myositis ossificans after total hip replacement and perioperative muscle ischemia.

It has been suggested that muscle ischemia could contribute to myositis ossificans and that the ischemia could result from prolonged retraction during surgery. Biopsy specimens of the gluteus medius muscle were taken at the beginning and the end of 30 primary total hip arthroplasties and the intracellular lactate and phosphocreatine (PCr) measured. Postoperative myositis ossificans was classified according to Brooker after 1 year, and the surface of the heterotopic bone projected above the greater trochanter in an anteroposterior roentgenogram was measured by planimetry. The findings suggest that muscle ischemia is not an important cause of myositis ossificans after hip arthroplasty, but elevated levels of lactate and lowered levels of intracellular PCr may occur as nonspecific responses to tissue trauma that through other mechanisms may lead to ossification.

Aged↗
PubMed1987

Force, relaxation and energy metabolism of rat soleus muscle during anaerobic contraction.

Isolated soleus muscle of rat was stimulated electrically (2 Hz) for 7 min under anaerobic conditions. Isometric twitch tension decreased progressively and was 30% of the initial value at the end of stimulation. The decline in relative force was similar to that previously observed in fast twitch muscle and soleus can thus not be termed fatigue-resistant under anaerobic conditions. Phosphocreatine (PCr) decreased from (mean +/- SD) 61.1 +/- 4.4 at rest to 4.0 +/- 1.8 mmol kg-1 dry muscle (d.m.) after 7 min of stimulation, while lactate increased from 3.7 +/- 1.6 to 30 +/- 8 mmol kg-1 d.m. Energy was thus derived from complete utilization of PCr and a low rate of glycolysis resulting in an almost unchanged calculated intracellular pH. It is concluded that tension decline in soleus muscle is not due to decreased intracellular pH but is more related to the capacity to regenerate ATP at a sufficient rate. Contraction and relaxation time of the twitch remained practically constant during the stimulation period. In contrast prolonged activation of fast-twitch muscle results in a slowing of the relaxation of the twitch (Sahlin et al. 1981) and it has been suggested that this is caused by the decrease of intracellular pH. The constancy of both relaxation time and calculated pH in the fatigued soleus muscle is consistent with the hypothesis that there is a connection between these two parameters. In contrast to the twitch, relaxation of tension after a tetanus was prolonged in soleus. Hence, it appears that the rate limiting step for relaxation is different for a twitch than for a tetanus in soleus.

Adenosine Triphosphate↗
PubMed1987

NADH content and lactate production in the perfused rabbit heart.

The influence of oxygen availability and absence of contractile activity on the NADH content and lactate production were investigated in the rabbit heart. Isolated hearts were perfused according to Langendorff with a modified Tyrode solution, saturated with a gas mixture containing either 95% O2:5% CO2 (control), 50% O2:5% CO2 in N2 (hypoxia), or 5% CO2 in N2 (anoxia). In another series of hearts cardiac arrest was induced by perfusion with Tyrode solution (95% O2:5% CO2) where the KCl concentration was increased to 15 mmol l-1 (hyperkalemia). Oxygen uptake (VO2) was similar in hypoxic and control hearts (P greater than 0.05), whereas lactate production was four-fold higher during hypoxia vs. control (P less than 0.01). Hyperkalemia resulted in a 60% decrease in VO2 (P less than 0.05), and no significant change in lactate production vs. control (P greater than 0.05). Both PCr and ATP were substantially decreased only during anoxia. Muscle NADH, whose changes reflect those within the mitochondria, averaged (+/- SE) 0.074 +/- 0.010, 0.153 +/- 0.016, 0.486 +/- 0.162 and 1.771 +/- 0.091 mmol kg-1 dry wt during control, hyperkalemia, hypoxia and anoxia, respectively. It is concluded that: muscle contraction during conditions of adequate oxygen supply results in an oxidation of mitochondrial NADH (presumably due to ADP stimulation of respiration), and a decreased oxygen availability results in an increase in NADH and an accelerated lactate production, although the VO2 is not affected.

Animals↗
PubMed1987

Effect of decreased oxygen availability on NADH and lactate contents in human skeletal muscle during exercise.

Eight men cycled for 5 min at 120 +/- 6 W (mean +/- SE) at which O2 uptake was 50% of its maximal normoxic value, breathing room air (21% O2; normoxia) on one occasion and 11% O2 in N2 (respiratory hypoxia/hypoxic--Resp. Hx.) on the other. Biopsies were taken from the quadriceps femoris muscle. Oxygen uptake during exercise was not significantly different between Resp. Hx (1.59 +/- 0.08 1 min-1) and normoxia (1.55 +/- 0.08 1 min-1). At rest, muscle lactate was the same under both conditions but was four times higher after Resp. Hx (33.2 +/- 5.2 mmol kg-1 dry wt) than normoxic cycling (8.6 +/- 1.0 mmol kg-1 dry wt; P less than 0.01). The muscle lactate/pyruvate (which is proportional to cytosolic NADH/NAD) was significantly higher after Resp. Hx.(76 +/- 19) than after normoxic cycling (26 +/- 2; P less than 0.05). At rest, analytically determined NADH averaged 0.14 +/- 0.02 mmol kg-1 dry wt under both conditions. However, exercise during Resp. Hx. resulted in a significantly higher NADH content (0.17 +/- 0.01) than exercise during normoxia (0.12 +/- 0.01; P less than 0.01). Indirect evidence indicates that the difference in muscle NADH reflects a difference in the mitochondrial redox state (Sahlin & Katz 1986). The increased muscle NADH during Resp. Hx. therefore indicates a relative lack of O2 at the cellular level (muscle hypoxia). It is suggested that the increased lactate production during Resp. Hx. is a consequence of the cellular adaptation to muscle hypoxia (i.e. increases in cytosolic ADP, AMP, Pi and NADH).

Adult↗
PubMed1986

The content of NADH in rat skeletal muscle at rest and after cyanide poisoning.

The concentration of NADH was determined a high-oxidative muscle (soleus) and a high-glycolytic muscle (extensor digitorum longus, EDL) from resting rats. The NADH content of freeze-clamped control muscles was 0.35 +/- 0.04 (mean +/- S.D.) and 0.31 +/- 0.04 mmol/kg dry wt. in EDL and soleus respectively, and increased to peak values of 0.58 +/- 0.05 (EDL) and 0.87 +/- 0.10 (soleus) after 10 min of NaCN treatment. The [lactate]/[pyruvate] ratio, which was not significantly changed in soleus and increased only slightly in EDL after NaCN incubation, shows that only minor changes occurred in the cytosolic NADH concentration. Provided that the major part of muscle NADH is located in the mitochondria it can be calculated that the mitochondrial NADH content in skeletal muscle at rest is about 36 (soleus) and 60% (EDL) of the anoxic value, respectively. These results are in contrast with previous studies with the surface-fluorescence technique, where mitochondrial NAD appeared to be almost completely reduced in resting skeletal muscle.

Animals↗
PubMed1986

Effect of prostacyclin on the severity of ischaemic injury in rabbit hearts subjected to coronary ligation.

The hypothesis that prostacyclin (PGI2) might have a direct cytoprotective action in ischaemic cardiac tissue was investigated. Myocardial ischaemia was induced in perfused rabbit hearts by ligating the left main coronary artery. Coronary flow, oxygen uptake, and turnover of lactate and purines were measured before and up to 120 min after coronary occlusion. After this, ischaemic tissue was separated from perfused myocardium, and levels of lactate, adenine nucleotides and creatine phosphate were determined in specimens from non ischaemic, ischaemic and border zones. PGI2 (final conc. 10(-7) M) was infused before or 30 min after ligation and the results were compared to those in control hearts. Coronary ligation reduced coronary flow and oxygen consumption by about 50%. The fractional extraction of lactate decreased from 20% to close to zero and purine release increased 5-fold. In the non-ischaemic area the tissue levels of ATP and creatine phosphate were high, with a low content of lactate, but in the ischaemic area the levels of ATP and creatine phosphate were considerably reduced and the content of lactate was high. Although coronary flow and oxygen uptake were elevated after treatment with PGI2, no change in lactate or purine turnover was observed. Neither the weight of the non-perfused myocardium nor the tissue levels of the adenine nucleotides, creatine phosphate and lactate were affected by PGI2 treatment. The data indicate that in this model, in which effects on cardiac work, collateral flow and platelets are eliminated, PGI2 does not limit ischaemic myocardial injury. Hence, the hypothesis of a direct cytoprotective action of PGI2 in ischaemic myocardial tissue was not supported.

Animals↗