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Biomedical subjects

L Kaijser

Publications and source records attributed to L Kaijser.

At least 163 records · Page 9Linked to original sources

Blood flow in the resting forearm during prolonged contralateral isometric handgrip at maximal effort.

1. In earlier studies we have shown that muscle contraction performed as handgrip at constant force, one third of maximal voluntary contraction (MVC), induces a rapid vasodilation in the resting contralateral forearm which in all probability is neurogenically mediated, followed by a relative increase in resistance.2. The maintenance of contraction at one third MVC for 2 min requires continuously increasing effort because of fatigue, as also evidence by the e.m.g. The biphasic response of the vascular bed may then be related to the increasing intensity of somatomotor activation which is needed to maintain contraction force, or, alternatively, to differences in vasomotor activity on initiation of and continued muscle activity.3. To elucidate these two possibilities blood flow in the resting forearm was measured during contralateral handgrips at constant maximal effort for 6 min (in which case force will drop) and compared to handgrip at constant force, one third MVC, for 2 min.4. The flow reaction during prolonged contraction at maximal effort was similar to that induced by contraction at constant force with a marked transient lowering of vascular resistance, although maximal vasodilation tended to be more pronounced and occur earlier.5. The results indicate that the rapid decrease in vascular resistance is related primarily to the initiation of somatomotor activity, whereas continued muscle contraction produces a relative increase in vasoconstrictor activity irrespective of changes in contraction effort.

Adult↗

Regulation of glycolysis in intermittent exercise in man.

1. Seven healthy male volunteers performed intermittent exercise (15 sec work--15 sec rest) at a high work load for 60 min and six subjects performed continuous exercise at an equally high load to exhaustion, which occurred after 4--6 min. 2. Muscle biopsies were obtained from the lateral portion of the quadriceps muscle before intermittent exercise and after the end of a work period and the end of the subsequent rest period at 5, 15, 30 and 60 min of exercise, as well as before, immediately after and about 15, 30, 60 and 180 sec after continuous exercise. 3. The reduction in glycogen content was smaller and glucose-6-phosphate, glycerol-1-phosphate, lactate and malate contents were lower after both work and rest periods in intermittent compared with continuous exercise, indicating a lower rate of glycolysis. 4. ATP and CP levels had decreased at the end of work periods in intermittent exercise but increased to slightly below basal in the subsequent rest periods. A still larger decrease in ATP and CP levels was found after continuous exercise to exhaustion and a progressive increase occurred over the 3 min of recovery. 5. In each rest period during intermittent exercise citrate levels increased to reach above basal. They increased also in the recovery phase after continuous exercise, although more slowly. 6. The findings support the assumption that ATP, CP and citrate act as regulatory factors of glycolysis in human muscle by retarding certain rate limiting steps. The increase in G-6-P/F-1-6-P2 ratio in rest periods of intermittent intense exercise and in the recovery phase of continuous intense exercise suggests that glycolysis is retarded at the phosphofructokinase reaction. 7. The factors mentioned may therefore contribute to the relative increase in lipid utilization during intense intermittent compared to continuous exercise.

Adenosine Triphosphate↗

Myocardial protection during aortic valve replacement. Physiological and metabolic effects of selective coronary perfusion on the fibrillating heart.

The physiological effects and certain aspects of cardiac metabolism were studied in 14 patients undergoing primary aortic valve replacement. The operations were performed under moderate hypothermia (30 degrees +/- 2 degrees C) and blood for coronary perfusion was taken from a sidebranch of the arterial line. The majority of the hearts went spontaneously into ventricular fibrillation at some stage of the operation. In spite of the high resistance measured in the coronary perfusion cannulae, an intraluminar coronary blood flow of 380 ml/min was recorded. The myocardial oxygen uptake decreased to 6.0 ml/min at 29 degrees C compared with 20.0 ml/min at 36 degrees C. The elevated coronary sinus lactate throughout the period of coronary perfusion and the increasing level of ASAT-enzyme indicated that this technique could not fully protect the myocardium from ischaemic changes. One patient died of myocardial infarction and two others needed vasopressor support postoperatively, in spite of documented effective coronary perfusion throughout the procedure. Cannulation of the coronary sinus is a valuable adjunct for the study of cardiac metabolism during ECC and it was accomplished without complications.

Adult↗

The relation between carbohydrate extraction by the forearm and arterial free fatty acid concentration in man. I. Forearm work with nicotinic acid infusion.

To see if the magnitude of carbohydrate extraction by working skeletal muscle in man is inversely correlated with the arterial free fatty acid (FFA) concentration as in the heart, eighteen healthy men were studied during dynamic forearm work with and without nicotinic acid. The extraction or release of glucose, lactate and pyruvate was determined by the simultaneous sampling of blood from the brachial artery (a) and a deep vein (dv) of the active forearm. Nicotinic acid decreased the arterial FFA concentration from 498 +/- 53 to 134 +/- 12 mumol per litre plasma and this caused a decrease in calculated extraction of FFA. However, it did not affect the extraction of glucose, which was of a magnitude similar to one third of the oxidative metabolism in both situations. One of the possible reasons of this difference compared to the human heart muscle is that the exercising skeletal muscle may utilize stored substrate to a greater extent, which makes possible shifts in substrate utilized for oxidation without changes in substrate extraction. Another reason may be that FFA utilization covers a far smaller proportion of oxidative metabolism in skeletal than in heart muscle already before nicotinic acid.

Adult↗

Heparin-induced release of lipase activity in the human forearm: an immunological study.

Low doses of heparin were injected into the brachial artery of three volunteers. The lipase activities in the deep vein of the same forearm, draining mainly muscle tissue, and in the artery were monitored over a 10-min period. Lipase activity, rapidly released by heparin in the deep vein, was immunologically similar to lipoprotein lipase (E.C. 3.1.1.3), i.e. (1) it did not react with antiserum against human post-heparin plasma hepatic lipase and (2) it was inhibited by an antiserum against bovine milk lipoprotein lipase, which cross reacts with human post-heparin plasma lipoprotein lipase. The evidence that human muscle contains lipoprotein lipase is discussed.

Adult↗

Differences in heparin-released lipolytic activity in the superficial and deep veins of the human forearm.

Various doses of heparin were given as a single injection into the brachial artery of each of twelve fasting healthy males. Plasma lipolytic activity was measured in samples obtained before and at frequent time intervals after heparin injection, in the artery and the deep and superficial veins of the same forearm. As little as 0.15 U heparin produced a rapid and detectable release of lipolytic activity in both deep and superficial veins. A series of tenfold increases in the dose produced correspondingly greater releases in the veins but the increments in the release were smaller than the increments in the dose. Three repeated 15 U doses of heparin, separated by 30 min, in the same subject gave a high degree of reproducibility of the release of lipolytic activity in both deep and superficial veins. 90% of the lipase activity in the vein was inhibited by 1 M NaCl. In all subjects the release of lipolytic activity was higher in the deep vein, which predominantly drains muscle, than in the superficial vein, which drains mostly subcutaneous tissues such as skin and adipose tissue. This indicates that muscle is a tissue of considerable importance as a source of post heparin plasma lipolytic activity.

Adipose Tissue↗

Muscle adaptation to extreme endurance training in man.

To evaluate the effect of extreme endurance training on muscle fibre composition and activities of oxidative enzymes in different fibre types biopsies were taken from vastus lateralis, gastrocnemius and deltoideus of elite orienteers. Comparisons were made between the (trained) leg muscles and the (relatively untrained) arm muscles, and with leg muscles of 16--18 years old boys. The orienteers had the same percentage type I fibres and vastus lateralis and gastrocnemius as in deltoideus, but higher percentage type I fibres in vastus lateralis compared with the controls. The similarity between trained and untrained muscle in the orienteers suggests that training had not caused the high percentage type I fibres which rather might be the result of selection of individuals with the best prerequisites for high oxidative capacity. However, the distribution of type II subgroups in the leg muscles of the orienteers differed from both their own deltoideus and leg muscles of the controls, the relationship IIA/IIB being altered in favour of the more oxidative IIA. The leg muscles of the orienteers also showed an increased occurrence of the normally IIC fibre. These latter findings point at the possibility of a training induced alteration in the subgroup pattern. Unlike in the controls there was no significant difference in succinate dehydrogenase activity, measured in single fibres, between type I and II fibres in gastrocnemius of the orienteers. Thus, type II fibres have the ability metabolically to adapt to high oxidative demands. This might to some extent be mediated by a conversion from IIB to IIA form.

3-Hydroxyacyl CoA Dehydrogenases↗

Utilization of blood-borne and intramuscular substrates during continuous and intermittent exercise in man.

1. Substrate utilization in the legs during bicycle exercise was studied in five subjects when performing intermittent intense exercise (15 sec work--15 sec rest) as well as continuous exercise during 60 min, with an almost identical average power output and oxygen uptake in both situations. 2. Muscle biopsies were obtained from vastus lateralis at rest, during, and after exercise in order to determine intramuscular lipid and carbohydrate utilization. The contribution from blood-borne substrates to total oxidative metabolism was determined by arterial-femoral venous (a-fv) differences for oxygen, FFA, glucose, and lactate and leg blood flow. 3. Intermittent and continuous exercise revealed a similar glycogen depletion and the intramuscular lactate accumulation was rather small. A similar uptake of blood-borne substrate (FFA, glucose) was found in both situations whereas a release of lactate only was observed in intermittent exercise. 4. ATP and CP levels oscillated between work and rest periods in intermittent exercise but were not resynthesized to resting levels at the end of the rest periods. The mainly aerobic energy release during each work period in intermittent exercise is partly caused by myoglobin functioning as an oxygen store; this factor was calculated to be more important than ATP and CP or lactate level oscillations. 5. The metabolic response to intermittent exercise was found to be similar to that found in continuous exercise with approximately the same average power output and oxygen uptake. This indicates that some factor in the intermediary metabolism, for instance citrate, functions as a regulator retarding glycolysis and favouring lipid utilization and an aerobic energy release in intermittent exercise.

Adenosine Triphosphate↗

Removal of exogenous plasma triglycerides in forearm muscle and subcutaneous tissue of hyper-and normotriglyceridaemic men.

Absolute arterio-venous removal and fractional removal of blood-borne exogenous triglyceride particles by skeletal and subcutaneous tissues were determined in eight normotriglyceridaemic and six hypertriglyceridaemic men. Estimations were made by simultaneously sampling blood from catheters inserted into a brachial artery, and in the distal direction, into a superficial and deep vein, draining subcutaneous tissue and skeletal muscle respectively. During the infusion of the fat emulsion IntralipidR for 3 hours steady arterial concentrations of exogenous TG particles were found, indicating first order kinetics. In all subjects absolute arterio-venous and fractional removal of triglycerides were about twice as high in skeletal muscle as in subcutaneous tissue. In skeletal muscle the fractional removal and absolute removal were significantly higher in normotriglyceridaemic than in hypertriglyceridaemic subjects (p less than 0.001). No decrease in removal with time was observed, which would have suggested saturation of removal sites. Mean fractional removal in skeletal muscle was significantly correlated with the k2 value determined by an intravenous fat tolerance test before the infusion study (r = 0.61, p less than 0.05). In subcutaneous tissue fractional removal was also significantly higher in normotriglyceridaemic subjects (p less than 0.05). The results suggest that in both skeletal muscle and subcutaneous tissue the removal system is impaired in hypertriglyceridaemic subjects. This finding supports the concept that a decreased elimination capacity in these tissues may partly account for triglyceride elevation in hypertriglyceridaemic subjects.

Adipose Tissue↗

Arterial concentration and forearm extraction of glucose and insulin during the early phase of a glucose infusion.

The concentrations of glucose and insulin were determined with high precision at half minute intervals in arterial and deep forearm vein blood after a bolus injection of glucose (4 g), followed by a constant i. v. infusion (200 mg/min), in four healthy subjects. The values for the deep vein were corrected for the transit time, which was determined by injection of Cardio-green. Arterial glucose peaked at the end of the bolus injection, venous glucose 1 1/2 min later. Arterial insulin reached its maximum later than glucose, after 2 1/2-4 min. The venous insulin reached its maximum later and was much lower than the arterial level, in two cases only around 50% of the arterial concentration. It is concluded that early after glucose administration there is a considerable extraction of both glucose and insulin by the forearm. Since the insulin extraction was quite variable venous insulin concentrations cannot be used for the assessment of early insulin response to glucose.

Adult↗

Effect of regional alpha- and beta-adrenergic blockade on blood flow in the resting forearm during contralateral isometric handgrip.

In a previous study we have shown that an isometric handgrip is accompanied by a rapid decrease in vascular resistance in the resting (contralateral) forearm, lasting for about 1 min, which in all probability is neurogenic. 2. In the present study the distribution of the vasodilatation was investigated by analysing O2 saturation in a deep vein, draining mainly muscle tissue. Some possible neurogenic mechanisms for the vasodilatation were tested by repeating the handgrip after local beta- and alpha-adrenergic blockade of the resting forearm with propranolol and phentolamine, respectively. 3. Without blockades the forearm vascular resistance decreased and the deep vein O2 saturation increase to similar degrees on contralateral handgrip. Propranolol markedly reduced both the decrease in resistance and the increase in deep vein O2 saturation. Phentolamine did not alter the initial decrease in resistance, but with phentolamine resistance continued to decrease after 1 min. 4. It is concluded that the rapid decrease in vascular resistance in the resting forearm on contralateral handgrip takes place, to a great extent, in muscle. It is mediated by neurogenic beta-adrenergic mechanisms and if the contraction is prolonged it gradually changes to a vasoconstriction mediated by alpha-adrenergic mechanisms.

Adult↗

Removal of exogenous triglycerides in human forearm muscle and subcutaneous tissue.

The removal of exogenous triglyceride (TG) in forearm muscle and subcutaneous tissue of 7 healthy male volunteers has been studied by nephelometric determinations of arterial-deep venous (a-dv) and arterial-superficial venous (a-sv) differences in concentration of fat particles. Exogenous TG was administered as a constant i.v. infusion of Intralipid over a period of 30 min at reat and another 15 min during forearm work. At rest a significant positive a-dv difference in fat particle concentration of 121 plus pr minus 21 mumol TG/l (mean plus or minus S.E.M.) was found, which correspondens to a fractional extraction of 1093 plus or minus 2.0%. Also the a-sv difference was significant, 81 plus or minus 14 mumol TG/l, 5.7 plus or minus 0.8% of the arterial concentration. During exercise no further significant removal was found. Thus both skeletal muscle and subcutaneous tissue seem to be able to remove exogenous TG in substantial amounts under resting conditions. In the exercising muscle, however, the direct removal of exogenous TG does not seem to be of significant importance.

Adult↗

Specific and unspecific removal of circulating noradrenaline in pulmonary and systemic vascular beds in man.

In order to study the extent and degree of specificity of the removal of circulating noradrenaline (NA) from the blood stream, during a single passage through the vascular beds of the lungs and of the forearm musculature of unanaesthetized, healthy young men, the following radiometric method was used: A misture of 3H-NA with 14C-inulin and 125I-labelled human serum albumin was injected proximally to the bed under study; six serial blood smaples were drawn distally to it, with about 15 s interval, and the disappearance of 3H-NA relatively to that of 14C-inulin and 125I-albumin was determined. 3H-NA was found to be removed from the blood stream in both these vascular beds. However, in the forearm the removal of 3H-NA was much greater, and apparently to a large extent due to specific trapping in the tissues, since the clearance of 3H-NA over the vascular bed of the forearm markedly exceeded that of 14C-inulin. During passage through the lungs removal of 3H-NA was less marked, and apparently largely unspecific, since it was initially essentially equal to that of 14C-inulin. This suggests that removal of circulating ergones of small molecular size, from the blood stream passing through the lungs, may occur initially by unspecific filtration/diffusion. Their subsequent fate would depend on whether the extraluminal tissues, supplied by the lung circulation, possess specific mechanisms for concentrating and/or inactivating each particular compound.

Adult↗

The effect of circulatory occlusion on isometric exercise capacity and energy metabolism of the quadriceps muscle in man.

Occlusion of the circulation to the quadriceps muscle for 20 min resulted in decreases in the muscle ATP and phosphorylcreatine (PC) contents of 1 and 32 per cent, respectively, and increases in ADP and AMP of 7 and 37 per cent. Decrease in PC was statistically significant after 4 min of occlusion, suggesting that the local intramuscular oxygen store was sufficiently depleted at this time as to be limiting to normal mitochondrial function. Pyruvate and lactate concentrations in muscle and the lactate to pyruvate ratio were significantly increased after 15 min of occlusion but not before. The calculated local oxygen store in the muscle was 2.0 mmol O2 - (kg dry muscle)-1. Local oxygen store depletion after 4 and 10 min of occlusion was estimated to be 40-50 and 90-100 per cent complete. Increasing time of pre-exercise occlusion resulted in decreased isometric endurance capacity. The observed decreases in endurance, however, were far greater than could be accounted for by any parallel decrease in the local muscle energy stores.

Adenosine Diphosphate↗

Extraction of endogenous plasma triglycerides by the working human forearm muscle in the fasting state.

The extraction of triglycerides (TG) by the working forearm was determined in eight healthy fasting men, both by the measurement of chemical arterial-deep venous (a-dv) TG differences and by the a-dv differences in TG radioactivity after endogenous labeling with tritiated palmitate. Measurements were made before and then during nicotinic acid infusion. Correction for plasma water shift in the forearm vasculature was made by estimating the (125I)albumin activity after an intravenous injection. The overall mean value +/- S.E.M. without and with nicotinic acid was for TG arterial concentration (mumol/1) 713 +/- 153 and 695 +/- 140, TG a-dv concentration difference (mumol/1)-14 +/- 7 and -6 +/- 4, TG arterial radioactivity (cpm/ml) 1650 +/- 469 and 1471 +/- 342, TG a-dv radioactivity difference 12 +/- 24 and -2 +/- 13. The average standard errors for the determinations of triglycerides were 0.85% and 1.5% for the chemical and the isotope methods, respectively. In conclusion, no significant average a-dv difference in TG concentration as determined by either the chemical or the isotope method was detected. With the standard errors achieved, however, a-dv differences of less than around 20 mumol/lcould not be discovered. Such an extraction of endogenous plasma TG could, if oxidized, account for about 25% of the oxygen extraction by the eercising forearm.

Adult↗