Influence of abdominal surgical trauma on substrate utilization by the human brain.
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Biomedical subjects
Publications and source records attributed to L Wiklund.
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Thirteen patients with gallbladder disease but otherwise healthy were studied in connection with cholecystectomy. Specimens of the lateral vastus muscle were taken by the percutaneous needle biopsy technique during anesthesia before surgery, on two occasions during surgery and 30 min after discontinuation of anaesthesia. The muscle samples were analysed for glycogen, lactate, citrate, ATP, phosphoryl creatine, creatine and water content. Citrate and lactate concentrations in muscle increased continuously throughout the study. There were no significant changes in the concentration of glycogen, phosphoryl creatine, and ATP in muscle tissue. The increase in citrate concentration is probably related to an augmented uptake and combustion of free fatty acids and 3-hydroxybutyrate in this situation. The data suggest that during anaesthesia and abdominal surgery an increase in the muscle citrate concentration may contribute to the modulation of carbohydrate utilization in skeletal muscle.
Abdominal surgery increases blood glucose concentration and peripheral release and splanchnic uptake of gluconeogenic substrates, including alanine. During trauma or sepsis, infusion of glucose fails to depress alanine conversion to glucose. The effect of intra-operative glucose infusion on splanchnic metabolism was examined in the present study. In eight patients undergoing elective cholecystectomy, splanchnic glucose metabolism was investigated before, during and immediately after surgery. Glucose was infused at a constant rate of 1 mmol/min. Splanchnic blood flow and arterio-hepatic venous differences of oxygen, glucose, lactate, glycerol, 3-hydroxybutyrate and alanine were measured. Eight other patients, who received saline instead of glucose, served as a control group. Infusion of glucose resulted in total inhibition of splanchnic glucose release before as well as during and immediately after surgery. This was observed, even before surgery, at an arterial glucose level which was lower than that in the control group at the end of and immediately after surgery, at which no decrease of the splanchnic glucose release was recorded. changes in neuronal and hormonal factors due to the surgical trauma are considered responsible for this difference in glucose homeostasis. Splanchnic alanine uptake increased during surgery in both groups, but tended to be somewhat lower in the glucose group. The arterial glycerol concentration and splanchnic uptake, as well as the arterial concentration and splanchnic release of 3-hydroxybutyrate, were reduced. It is concluded that an intravenous infusion of glucose at the rate of 1 mmol/min during abdominal surgery (a) increases the arterial blood glucose level and abolishes splanchnic glucose release, (b) reduces, but does not totally prevent the increase in splanchnic uptake of gluconeogenic substrates, and (c) diminishes lipolysis and the formation of 3-hydroxybutyrate.
1. 5,6-dihydroxytryptamine (5,6-DHT) or a lesion of the raphe centralis superior (RCS) cause significant decreases in the serotonin (5-HT) content and significant increases in the tyrosine hydroxylase activity in the locus coeruleus (LC) of the rat. This suggests that noradrenaline (NA) synthesis is controlled by serotonin-containing neurons in the raphe system via their terminals in the LC. 2. Radioautography after intraventricular infusion of tritiated serotonin (3H-5-HT) and biochemical determinations of endogenous 5-HT content showed an almost complete disappearance of serotoninergic axonal varicosities and content in the LC region 10-15 days after intraventricular administration of 75 micrograms of 5,6-DHT. Two to 4 months after neurotoxin administration, 5-HT fibers had regrown in the LC but, contrary to the normal innervation pattern, the majority of them invaded the medial most portion of the nucleus and the adjacent subependymal region. The LC region regained almost all of its endogenous 5-HT content in the same time period. 3. Functional recuperation of these 5-HT fibers was demonstrated by the fact that the RCS had, after regeneration, the same functional control on NA synthesis as in the normal animal.
The inferior olive of the cat has, with fluorescence histochemistry, been shown to receive a rich serotoninergic innervation. The distribution of this innervation agrees with the topography of spinal afferent termination as well as the olivo-cerebellar climbing fiber projection. This indicates that different olivary compartments are under different serotoninergic influence. The serotoninergic innervation of the dorsal accessory nucleus (DAO) of the inferior olive of the rat has been identified with electron microscopic radioautography after labelling with 3H-serotonin. The serotoninergic varicosities contain microcanaliculi, tubular-vesicular organelles and large granular vesicles. Few of the serotoninergic varicosities engage in typical synaptic junctions. However, non-junctional varicosities often display other ultrastructural indications of polarity and directed transmitted release. Electrophysiological results indicate that the harmaline-induced tremor, as well as the tremor component of the "serotonin-syndrome", depends on the serotoninergic innervation of the inferior olive. Thus, the sensitivity of different olivary compartments to the induction of rhythmic, synchronous activity by harmaline parallels the distribution of serotoninergic innervation. Neurotoxic destruction of the serotoninergic innervation leads to decreased sensitivity to harmaline. Further, the serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine, as well as monoamine oxidase inhibition + L-tryptophan loading, leads to rhythmic mass climbing fiber activity in the cerebellum and whole body tremor. A neuromodulatory effect of serotonin on the olivary action potential mechanisms is proposed.
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Central haemodynamics and blood gases were measured in 26 patients undergoing elective aortic surgery for atherosclerotic or aneurysmal disease. Recordings were made at seven defined time points, starting before anaesthesia and ending 30 min after declamping of the aorta. The patients were randomly divided into two groups, one receiving heparin at an early stage and the other at a late stage of the operative procedure. A declamping shock phenomenon could be prevented by thorough blood and fluid replacement. After removal of the aortic clamp the cardiac output increased, except in a few patients who were considered preoperatively to be poor risks. A significant decrease in arterial oxygen tension and increase in pulmonary artery and pulmonary capillary wedge pressures occurred in patients receiving heparin at a later stage. The effect of heparin points to possible intravascular coagulation and pulmonary microembolism during the operation.
The aorta and common iliac arteries were clamped for 2 hours in 27 pigs under general anaesthesia. Ten pigs were heparinized and the other 17 did not receive heparin. A further 5 pigs were used as sham-operated non-heparinized controls. Blood gases and also mean arterial, pulmonary arterial, pulmonary capillary wedge and left atrial pressures were recorded before, during, and after clamping. In the non-heparinized pigs there was a significant increase in pulmonary capillary wedge pressure during and after clamping of the aorta, slight variations in the left atrial pressure (measured in 5 non-heparinized pigs) and a decrease in PaO2, which was especially pronounced after declamping of the aorta. No such changes occurred in heparinized or control animals. The discrepant results in heparinized and non-heparinized animals indicate a mechanism influenced by heparin. Clamping and declamping of the aorta obviously accelerated the changes in the non-heparinized animals. It is suggested that these changes are caused by pulmonary embolism induced by the clamping and declamping of the aorta. Alterations in the pulmonary circulation indicated that the mean pulmonary capillary wedge pressure is not a reliable indicator of left ventricular filling pressure during aortic surgery.
Using Falck-Hillarp fluorescence histochemical and radioautographic techniques, it has been found that, in addition to the well-known catecholaminergic cells, the locus coeruleus (LC) of the cat contains a sizeable component of indolaminergic neurons. Indolaminergic cell bodies occur in all subdivisions of the LC complex. They are most numerous in the LC proper and subcoeruleus area, but are also present in the medial and lateral parabrachial, and Kölliker-Fuse nuclei. In all, the indolaminergic cells are estimated to make up 7-10% of the monoaminergic neuronal population of the LC complex. With the exception of the Kölliker-Fuse nucleus, where somewhat larger cells occur, the indolaminergic cell bodies in different parts of the LC complex share a common fluorescence histochemical appearance. They display round to fusiform shapes and measure 30 x 18 micron on the average, which makes them cytoarchitectonically similar to the small type of noradrenergic cells in the LC. The formaldehyde-induced fluorescence of the indolaminergic cells in the LC complex was analyzed microspectrofluorometrically and the recorded excitation and emission spectra (maxima at 370 and 530 nm, respectively) were found to be identical with those recorded from midline raphe neurons. No evidence of noradrenaline content was found in the indolaminergic cells of the LC. Radioautographic experiments after intratissular injections of tritiated serotonin showed that the indolaminergic cells of the LC complex possess uptake mechanisms for serotonin. Taken together these results provide strong evidence for serotonin being the transmitter of the indolaminergic neurons discovered in the LC of the cat.
The nervous input to the subcommissural organ (SCO) of the rat has been investigated with Falck-Hillarp fluorescence histochemistry and electron microscopical techniques. Previous fluorescence histochemical observations of a dense plexus of serotoninergic nerve fibres in relation to the basal SCO were confirmed. Electron microscopically, unmyelinated fine varicose axons ranging in size from 0.1--0.6 micrometer were observed to penetrate into the SCO hypendyma. Boutons and presynaptic varicosities filled with a diversity of round and elongated clear vesicles, and occasional large dense cored vesicles establish asymmetric (Gray's type I) synaptic contacts with the basal processes and somata of the SCO ependymal and hypendymal cells. A typical varicosity in synaptic contact with an SCO cell contains a population of approximately 85% clear, elongated vesicles 45 X 60 nm in diameter, 15% clear, round vesicles 50 nm in diameter, and 1--2% large dense cored vesicles with a vesicle diameter of about 85 nm and a dense core diameter of 50--55 nm. The mean length of the postsynaptic membrane specialization was found to be 0.5 micrometer. Experiments with specific neurotoxic drugs revealed that the nerve terminals in synaptic contact with the SCO cells are identical to the fibres of the serotoninergic plexus identified fluorescence histochemically. Thus, an intraventricular injection of either 5,6-dihydroxytryptamine or 5,7-dihydroxytryptamine induced typical degenerative changes in most of the boutons in synaptic contact with the SCO cells, and also a disappearance of the yellow fluorescent nerve plexus. It is concluded that the SCO of the rat receives a dense plexus of serotonin-containing nerve fibres which form typical synaptic contacts with the specialized ependymal cells of the SCO and that these fibres may constitute the only direct nervous input to the organ. The degeneration of the serotoninergic synapses elicited a long-lasting, pronounced increase in the secretory activity of the SCO. Despite long survival times after the treatment with neurotoxic drugs, we found no evidence of regenerative restitution of the serotoninergic innervation nor normalization of the secretory activity of the SCO. The observed inverse relationship between secretory activity and serotoninergic innervation is in line with previous observations which indicate that the 5-hydroxytryptamine input to the SCO ependymal and hypendymal cells exerts a powerful inhibition on their protein synthetic machinary.
Specific neurotoxic destruction of the serotoninergic innervation of the subcommissural organ of the rat is followed by an efficient reinnervation by collateral sprouting of non-monoaminergic axons, which normally do not innervate the SCO cells. Morphologically, the reinnervating fibres totally replace the serotoninergic synapses lost by the lesion, but, functionally, they fail to substitute for the potent inhibitory control of secretory activity normally exerted by the serotoninergic innervation. It is possible that the observed reinnervation by foreign synapses explains why the regrowing serotoninergic neurons fail to re-establish their connections with the SCO.
In eighteen patients with hypertension the effect of a splanchnic block was studied with respect to the plasma renin activity (PRA) in the renal vein and to the renal haemodynamics. A significant reduction of the PRA was noted during splanchnic block, both in kidneys with arterial stenosis, and in those without. The decrease in renin activity took place despite a simultaneous decrease in renal vascular resistance, which in itself should increase the secretion of renin. This supports the view that the sympathetic nervous system dominates over the baroreceptors in patients with hypertension at the pressure levels investigated and if the sodium intake is restricted.
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