Showing papers in "Acta Physiologica Scandinavica in 1963"

The Permeability of Capillaries in Various Organs as Determined by Use of the ‘Indicator Diffusion’ Method

Abstract: Crone, C. The permeability of capillaries in various organs as deter-mined by use of the ‘Indicator Diffusion’ method. Acta physiol. scand. 1963. 58. 292—305. — The theory of a single injection technique, the ‘Indicator Diffusion’ method, for quantitative studies of capillary permeability is developed. It is shown that the permeability of a capillary area can be expressed by three parameters: the initial extraction (E) of test substances added in a single injection to the blood flowing to an organ, the blood flow (Q) and the surface area (A) of the capillaries. The equation relating these figures is: P = (=/A) × loge1/(1—E). The permeability coefficients of capillaries in kidney, liver, lung, brain and hind limb to inulin and sucrose are reported. It is found that the permeability of capillaries varies considerably from organ to organ. It is questioned whether the pore model adequately describes the functional characteristics of the capillaries in the muscles. The existence of pores should result in a pronounced deviation of the ratio between the permeability coefficients for sucrose and inulin from the ratio between the free diffusion coefficients. This was not found to be the case.

An improved method for fluorimetric determination of small amounts of adrenaline and noradrenaline in plasma and tissues.

Abstract: Haggendal, J. An improved method for fluorimetric determination of small amounts of adrenaline and noradrenaline in plasma and tissues. Acta physiol. scand. 1963. 59. 242–254. — By the introduction of several modifications of the trihydroxyindole method for the determination of adrenaline and noradrenaline appreciable improvement of the sensitivity has been obtained. The blank values have been considerably reduced and stabilized by substituting dimercaptopropanol (BAL) in sodium sulfite solution for ascorbic acid. The eluate volume has been reduced and the degree of purification has been increased by a modified ion-exchange procedure (Dowex 50 W-X8). Deproteinization of plasma before the column procedure could be omitted. When this procedure was applied to 10 ml plasma obtained from normal persons at rest, noradrenaline spectra, with two activation peaks, were usually obtained. The average concentration of the noradrenaline was 0.3 ± 0.11 μg per litre of plasma. Normally no adrenaline was found. Noradrenaline occurred in plasma in both free and conjugated form.

Solubility of acetylene in lung tissue as an error in cardiac output determination with the acetylene method.

Abstract: The solubility of acetylene in lung tissue is measured by a rebreathing technique. Enough acetylene is dissolved in the lung tissue to simulate an extra gaseous lung volume between 0.274–0.48 liters. This should give an error of 7–12 % in cardiac output determination with the acetylene rebreathing method.

Circulatory studies in well trained athletes at rest and during heavy exercise. With special reference to stroke volume and the influence of body position.

Abstract: Eight well trained athletes (cyclists) with large dimensions of the circulatory system were studied with heart catheterization at rest and during exercise at 800 and 1,600 kpm/min both while sitting and supine. The results are compared with data from non-athletes. The cardiac output at rest and during work showed the same relation to the oxygen uptake as in nonathletes. The cardiac output was less in the sitting than in the supine position by 2.6 1/min at rest and 1.8 1/min during heavy work, due to a smaller stroke volume in the sitting position in both groups. On transition from rest to exercise the stroke volume increased 9 % in the supine and 48 % in the sitting position. After these initial changes the stroke volume remained constant during continued exercise with the heavier load in both body positions. The difference in stroke volume between supine and sitting position averaged 43 ml at rest and 9 ml during heavy exercise. The stroke volume during work in the supine position showed the same relation to the blood volume as in the nonathletes. The stroke volume was larger than expected from the size of the heart, when compared with the previously demonstrated relationship in nonathletes. The rate of work, performed at pulse rate 170, bore approximately the same relationship to the stroke volume during exercise in both groups. The larger oxygen transport capacity of these athletes as compared to nonathletes is explained by a larger stroke volume. During exercise the ventricular filling pressures were higher than in nonathletes.

Lactic acid assay with L(plus)lactic acid dehydrogenase from rabbit muscle.

Abstract: Lundholm, L., E. Mohme-Lundholm and N. Vamos.Lactic acid assay with L(+)lactic acid dehydrogenase from rabbit muscle. Acta physiol. scand. 1963. 58. 243–249. — Lactate assay with L(+)lactic acid dehydrogenase from rabbit muscle and with DPN involved the problem of quantitatively reducing lactate to pyruvate. The problem was overcome by use of a solution with a high pH, by an excess of DPN, and by addition of a carbonyl reagent e.g. semicarbazide or hydrazine, which trapped the formed pyruvate. Hydrazine was found to be preferable to semicarbazide since it appeared to bind pyruvate more effectively. It was thus possible to carry out the reaction, with a 100 per cent recovery, at pH = 9.0. This was advantageous because, at pH > 9.0, hydrazine and semicarbazide rapidly formed products with DPN that absorbed at 340 mμ, giving a high blank value that varied greatly with the pH of the solution and seriously affected the precision of the method. Unlike hydrazine, moreover, semicarbazide reacted with formed DPNH in the presence of atmospheric oxygen, so that the extinction of DPNH decreased.

Nervous and local chemical control of pre-capillary sphincters in skeletal muscle as measured by changes in filtration coefficient.

Abstract: The influence of nervous and local chemical factors on the pre-capillary sphincter section of the muscle vascular bed has been studied in terms of changes in the filtration coefficient (CFC). The results suggest that the vasoconstrictor fibres, beside their powerful influence on the resistance and capacitance vessels, affect also the pre-capillary sphincters, which determine the number of capillaries open to flow. However, the influence exerted by the centrally controlled vasoconstrictor fibres on the pre-capillary sphincters in the skeletal muscles is rapidly overcome by ‘vasodilator metabolites’, accumulating when flow is reduced or metabolism is increased. Such local metabolic factors exert an especially powerful control of the sphincter section as compared with the neurogenic influence. Thus CFC in the skeletal muscles tends to rise at any decrease of blood flow/ tissue metabolism ratio e. g. from ‘resting’ values around 0.015 up to 0.04—0.05, during muscular exercise; an increase also occurs when flow is reduced. Flow reduction following mechanical arterial obstruction induces a relatively greater CFC increase than when flow is reduced by the constrictor fibres, which unmasks their weak but still significant influence on the pre-capillary sphincter section.

Cellular localization of monoamines in the median eminence and in the infundibular stem of some mammals.

Abstract: A histochemical analysis of the monoamines which are strongly accumulated in the median eminence and the proximal part of infundibular stem of all species examined (mouse, rat, guinea pig, hamster, rabbit, and cat) was performed with the help of a highly specific and sensitive fluorescence method. Strong evidence was obtained for the view that the monoamines are localized in very high concentrations to the terminal parts of non-sympathetic nerve fibres, which — mainly at least — converge to the primary plexus of the hypophyseal portal system. The capillaries are densely and closely surrounded by the nerve fibres.

Studies on the elimination of exogenous lipids from the blood stream. the kinetics of the elimination of a fat emulsion and of chylomicrones in the dog after single injection.

Abstract: The kinetics of the elimination from the blood stream of intravenously injected fat emulsion (Intralipid®) and of chylo-micrones have been studied in the fasting dog. The elimination was estimated by determination of the arterial whole blood glyceride concentration and subtraction of the basal glyceride concentration. The same type of elimination was found in all dogs studied. The elimination consisted of two phases operating above and below a glyceride concentration of around 1.1 mM (increase above basal level) respectively. Above the concentration 1.1 mM the elimination was linear, i.e. a constant amount of glycerides was eliminated per unit time. The mean value for the elimination in this phase was 0.05 mmole/l blood per minute. Below this concentration the elimination was single exponential, i.e. a constant fraction was removed per unit time. The mean value found for this elimination was 5 per cent per minute. No greater difference was observed between the synthetic emulsion and chylomicrones. The physiological significance of the maximal elimination rate above 1.1 mM and the concentration dependent elimination below is briefly discussed.

Primary afferent depolarization evoked from the sensorimotor cortex.

Abstract: Stimulation of the sensorimotor cortex evokes dorsal root potentials (DRP) in the lumbo-sacral cord. Primary afferent depolarization is evoked in group Ib and group II muscle af-ferents and cutaneous afferents but not in Ia afferents. The effects are mediated by the pyramidal tract. There is spatial facilitation between the paths from primary afferents and cortex. It is concluded that the pyramidal tract acts on primary afferents by giving excitatory action to interneurones of spinal reflex arcs to primary afferents.

Biological Effects of an Unsaturated Trihydroxy Acid (PGF2α) from Normal Swine Lung Prostaglandin and Related Factors 13

Abstract: Anggard, E. and S. Bergstrom. Biological effects of an unsaturated trihydroxy acid (PGF2α) isolated from normal swine lung. Acta physiol. scand. 1963. 58. 1—12. — The effects on various isolated smooth muscle organs and on the cardiovascular system of cats and rabbits were studied. The rabbit duodenum, guinea-pig ileum, rat duodenum and colon, hen rectal caecum, guinea pig uterus and rat uterus were stimulated to a slow contraction. Rabbit duodenum and oestrogen treated rat uterus proved the most sensitive organs, with a threshold concentration as low as 0.001 μg/ml. I.v. injection in rabbits of 15—30 μg/kg caused a fall in blood pressure, with no changes in right ventricular pressure or heart rate. I.v. injection of 15—30 μg/kg in cats increased right ventricular pressure, with a concomitant depression of the systemic blood pressure. A bradycardia, which could be abolished by vagotomy or atropine, occurred 10—30 seconds later. It was concluded, that in cats the fall in blood pressure resulted partly from a reduced cardiac output due to constriction of the pulmonary vessels, partly from the bradycardia, and to a minor extent only from direct effects on muscle vessels.

Studies on the relationship between flow resistance, capillary filtration coefficient and regional blood volume in the intestine of the cat.

Abstract: Folkow, B., O. Lundgren and I. Wallentin. Studies on the relationship between flow resistance, capillary filtration coefficient and regional blood volume in the intestine of the cat. Acta physiol. scand. 1963. 57. 270—283. — The relation between flow resistance, regional blood volume and capillary filtration coefficient (CFC) in the cat's intestine has been quantitatively studied at different levels of vascular smooth muscle activity, and compared to the vascular bed of the skeletal muscles. The resistance vessels of booth these vascular circuits maintain a considerable ‘basal tone’, but the intestine is far richer vascularized, which is obvious from the figures given for flow resistance, regional blood volume and CFC at comparable levels of vascular tone, including maximal vasodilatation. Intestinal CFC is both in absolute and relative terms higher than in the skeletal muscles, as reflected by a definitely larger CFC/blood flow ratio over the entire range of vascular tone. CFC thus increases considerably when vascular tone is reduced and reaches very high figures at maximal vasodilatation. This is thought to reflect an opening up of additional capillaries due to relaxation of their ‘precapillary sphincters’. Reasons arc given for the belief that the glandular mucosal portion is far better vascularized than the smooth muscle portion of the intestine and at maximal vasodilatation CFC of the mucosal portion may be of the order of 1 ml/min Hg/mm/100 g of tissue. Such a figure is in fact comparable to the renal glomerular filtration, when expressed in the same way.

Chemical and histochemical evaluation of the distribution of catecholamines in the rabbit and guinea pig hearts.

Abstract: Chemical determinations of nor adrenaline (NA), adrenaline (A), and dopamine (DA) were made in the right and left atria and ventricles (RA, LA RV. LV) of rabbit and guinea pig hearts. The concentration of these amines was also studied in the sino-auricular (SA) node of the rabbit. Some of these tissues were also examined for the distribution of catecholamines using a histochemical fluorescence technique. NA was the predominant catecholamine present in atria and ventricles. It was more concentrated in the RA than LA and in the RV than in the LV of the rabbit and guinea pig. In the latter KA was distinctly higher in the atria than in the ventricles. By contrast A was more concentrated in ventricles than in atria of both species and accounted for about 5–10 per cent of the total catecholamine content. DA was found pre-dominantely in the atria, more in RA than in LA. High concentrations of DA were found in the SA node region. Histochemical studies on rabbit tissues showed that the catecholamines were found within nerve structures. A high density of fluorescent fibers and fiber bundless was found in the SA node region. An excellent correlation between the histochemical and chemical findings was obtained when both NA and DA were considered.

Determination of the hepatic galactose elimination capacity after a single intravenous injection in man: the reproducibility and the influence of uneven distribution.

Abstract: Tygstrup, N. Determination of the hepatic galactose elimination capacity after a single intravenous injection in man. The reproducibility and the influence of uneven distribution. Acta physiol. scand. 1963. 58. 162–172. — The hepatic galactose elimination capacity was determined from the disappearance curve in blood after a single intravenous injection. Using conventional principles for the calculation the results in repeated experiments were reproducible within 10 per cent. Comparison of the results obtained by this method with those of an infusion method showed that the latter were consistently smaller. This difference, amounting to an average of 15 per cent, might be caused by uneven distribution of galactose between its intra- and extravascular volume of distribution. From theoretical considerations it was deduced that the uneven distribution might be corrected for by parallel displacement of the arterial concentration curve along the time axis. Experiments with continuous infusions at different rates indicated that on the average the curve of the mean concentrations in the body was delayed 7 min in relation to the arterial curve. When the single injection experiments were corrected for this delay, the difference between the results of single injection and infusion experiments disappeared.

The Physiology of the Swimbladder in the Eel Anguilla Vulgaris

Abstract: Steen, Johan B. The physiology of the swimbladder of the eel, Anguilla vulgaris. III. The mechanism of gas secretion. Acta physiol. scand. 1963. 59. 221–241. — The mechanism of gas secretion has been investigated by analysis of blood samples from arteries and veins at both poles of the rete associated with the gas gland. During gas deposition, as measured by gas analyses of the bladder content, the blood is enriched in lactic acid as it circulates in the bladder epithelium. The pH of this blood is about 1 pH unit lower than that in the blood entering the rete from the gills. Part of the lactic acid diffuses from venous to arterial capillaries in the rete. A gradient in gas tension across the rete is produced partly by the existing acid gradient, and partly by the delayed response of the gas tension to the change in acid content which the blood undergoes as it passes the rete. The results strongly support the theory that gas concentration occurs by a counter current multiplication in the rete of a primary gradient induced by the addition of acid electrolytes to the venous blood. The measured values on acid content, pH and blood flow agree very well with the values which have been found adequate, through calculations on the potentialities of such systems, to produce gas pressures higher than those actually measured, and it is concluded that this secretory mechanism will explain secretion of all the atmospheric gases even in deep sea fishes.

Excitatory and Inhibitory Effects of Vagus Stimulation on Gastric Motility in the Cat

Abstract: In acute experiments on cats gastric motor responses were recorded during vagal stimulation with a constant frequency but with different values of impulse duration and voltage. With very low values cardiac responses only were obtained. With higher values pure excitatory motor effects of the stomach were elicited, but when the values were increased above a certain point a gradual depression of the response was observed. After atropine, the gastric motor responses were abolished, and pure relaxation was the result of stimulations which previously had given rise to partially depressed excitatory responses. It is suggested that two groups of efferent fibres, influencing gastric motility are present in the vagus nerve. According to the strength-duration diagram both fibre groups are of smaller caliber than the cardioinhibitory fibres, the inhibitory fibres being the thinnest ones. The excitatory fibres appear to be cholinergic, whereas the inhibitory effect seems to be mediated by some other transmitter substance.

Mast cell content and fatty acid metabolism in the epididymal fat pad of obese mice.

Abstract: Hellman, B., S. Larsson and S. Westman. Mast cell content and fatty acid metabolism in the epididymal fat pad of obese mice. Acta physiol. scand. 1963. 58. 255–262. — The changes in the mast cell content of the epididymal and subcutaneous adipose tissues were studied in two different types of obesity in mice. Both with the obesity induced by goldthioglucose and that associated with the American variety of the obese-hyperglycemic syndrome there was a considerable accumulation of mast cells in the fat depots. While the relative number of mast cells was calculated as 3 per 100 epididymal fat cells in the lean controls, it was more than 50 for the obese-hyperglycemic animals. This finding stresses the importance of expressing metabolic data on lipogenesis directly in terms of the fat cells and not per tissue weight, nitrogen or DNA, when comparing the adipose tissue in normal and obese individuals. The greatly increased mast cell content of the adipose tissue in obesity would be consistent with previous work on the rat, in which it was suggested that the lipase activity of the adipose tissue is concerned with accumulation of fat in depots. However, in so far as heparin did not influence the release of free fatty acids or clearing factor lipase from the isolated epididymal adipose tissue, no in vitro effect of heparin was demonstrated.

The tissue distribution of radioactivity following the injection of varying levels of fatty acid labeled chylomicrons in the rat.

Abstract: Belfrage, P., B. Borgstrom and T. Olivecrona. The tissue distribution of radioactivity following the injection of varying levels of fatty acid labeled chylomicrons in the rat. Acta physiol. scand. 1963. 58. 111–123. — H3-palmitic acid labeled chylomicrons in doses of 4–124 mg lipid were injected intravenously into rigorously carbohydrate-fed rats. The radioactivities in blood, liver, adipose tissue, spleen, lungs, kidneys, and muscles were studied. For doses of 4 to 33 mg lipid the disappearance of label from the blood followed an exponential rate which was similar for these doses and corresponded to half-lives of 2.2 to 3.5 minutes. The maximal radioactivities found in the liver were also similar for these doses and ranged from 40 to 51% of the injected radioactivity. For doses of 64 and 124 mg lipid the disappearance curve was more complex and the label disappeared more slowly from the blood. The maximal radioactivity found in the liver was also decreased. It is concluded that at these doses the system was overloaded. The spleen and the lungs took up significant amounts of chylomicron fatty acids as evidenced by initial peaks in the radioactivity curves for these tissues. The kidneys, the heart, and the muscles showed a slower rise of radioactivity and presumably took up mainly recirculated fatty acids. The adipose tissue also seemed to take up mainly recirculated fatty acids.

Effect of adenine nucleotides on catecholamine release and uptake in isolated adrenergic nerve granules.

Abstract: On addition of 1–5 mM adenosine triphosphate (ATP) the spontaneous loss of noradrenaline from a suspension of adrenergic nerve granules is retarded or prevented. Adenosine diphosphate (ADP) exerts a similar effect while adenosine monophosphate (AMP) has little action. ADP and ATP also enhance the uptake of catecholamines from the incubation fluid. This effect is observed even with low amine concentrations in the incubation fluid in contrast to the uptake without addition of ATP. The ATP-dependent uptake is inhibited by reserpine.

Catecholamine Release and Uptake in Isolated Adrenergic Nerve Granules

Abstract: Isolated storage granules from bovine splenic nerves, incubated in neutral isotonic K-phosphate give off noradrenaline at rates rapidly increasing with temperature. Noradrenaline in concentrations of 10—20 μg/ml in the incubation fluid inhibits or prevents the release. The noradrenaline thus retained is released at the normal rate after removal of the amine in the incubation fluid. After depletion, the granules are able to take up noradrenaline and adrenaline to about the original content when exposed to catecholamines in concentrations of 10—20 μg/ml, suggesting a limited storage capacity of the granules. It is suggested that the noradrenaline in the adrenergic nerve terminals is partly present in a free pool available for immediate release during nerve stimulation and that a lowering of the concentration in this pool causes the granules to give off the stored transmitter until an equilibrium is reached. The following resynthesis is assumed to continue until the free pool has reached a concentration preventing further release from the granules. This concentration is about the same as that normally found in bovine splenic nerves.

Decerebrate control of reflexes to primary afferents.

Abstract: Dorsal root potentials (DRP) have been compared in decerebrate cats before and after transection of the spinal cord. The DRPs evoked from group I muscle afferents of flexor and extensor muscle are either unchanged or slightly decreased after transection of the cord. In the spinal state the DRP evoked from cutaneous afferents has two components: 1) Component I, representing primary afferent depolarization (PAD) in cutaneous afferents, has brief latency and is of equal size in the decerebrate and spinal states. 2) Component II and the DRPs evoked from high threshold muscle and joint afferents are ascribed to the flexor reflex afferents (FRA) and represent PAD in the FRA. This action cannot be evoked in the decerebrate state. The FRA act on the same primary cutaneous afferents in which component I is evoked. It is concluded that there is a tonic inhibition in the decerebrate state of transmission from the FRA to the FRA but there is neither inhibition of the short latency path from cutaneous afferents to cutaneous afferents nor of the paths from group I muscle afferents to Ia, Ib and cutaneous afferents. The cord dorsum potentials (CDP) have also been compared before and after transection of the cord. The release after brain stem lesions of the CDPs and DRPs evoked from the FRA is compared with the release of actions from the FRA to motoneurones.

Effects of bretylium, reserpine, guanethidine and sympathetic denervation on the noradrenaline content of the rat submaxillary gland.

Abstract: After sympathetic denervation the noradrenaline content of the rat submaxillary gland decreased slowly during the first 8 hours and disappeared completely in 24 hours. Reserpine and guanethidine caused depletion of noradrenaline from denervated as well as innervated glands. In the case of reserpine the denervated gland was slightly less depleted (p < 0.05). The noradrenaline depletion produced by treatment with these two drugs and by sympathetic denervation was significantly reduced by simultaneous injection of bretylium. In addition bretylium had a releasing effect, not as striking as that of rescrpine and guanethidine, but highly significant. The implications of these results are discussed.

Handling of glycerol in the kidney.

Abstract: Kruhoffer, P. and O. I. Nissen. Handling of glycerol in the kidney. Acta physiol. scand. 1963. 59. 284–294. —Essentially complete reabsorption of glycerol (and urine/plasma ratios below one) was observed in cats at low filtered loads. With increasing filtered loads the reabsorption rate continued to rise and the reabsorption fraction converged upon a value of about 0.4. The rate of metabolic conversion of glycerol in the kidneys – simultaneously determined from measurements of renal blood flow and arterio-venous deficits –exceeded the reabsorption rate at low filtered loads whereas the relation was undoubtedly reversed at high filtered loads. Stop-flow experiments indicated that the most distal parts of the nephron are sparsrly permeable to glycerol and that concentrations below that of arterial plasma may arise in proximal parts. The observations ma)- be accounted for on the assumptions that reabsorption at low filtered loads is predominantly a conversion reabsorption (diffusion from the tubular lumen into tubular cells maintained by a metabolic convcrsion inside the cytoplasm) and that at high filtered loads well above the level of saturation of the glycerol converting enzymes it is essentially due to transcellular back-diffusion through the (proximal) tubular cells. I'he pattern of renal excretion of glycerol may thus be interpreted without resorting to special transmembranr transfer mechanisms.