Biomedical subjects

L Wiklund

Publications and source records attributed to L Wiklund.

At least 145 records · Page 8Linked to original sources

PubMed1986

The influence of abdominal surgical trauma on the exchange of blood-borne amino acids in the human leg.

Associated with surgical trauma is an increased release of gluconeogenic substrates from the periphery. The present study was undertaken to investigate the peripheral exchange of blood and plasma amino acids as well as some other gluconeogenic substrates (lactate and glycerol) in connection with abdominal surgery. Measurements of leg blood flow and femoral arterio-venous substrate differences were made before, during and immediately after elective cholecystectomy. Blood and plasma concentrations of most amino acids except alanine decreased during and immediately after surgery. Simultaneously there was an increased release of several of the amino acids as well as lactate and glycerol from the leg. The total release of plasma amino acids from one leg in the immediate postoperative period was about 2.5 times as high as before surgery. The turnover rates of amino acids as well as the changes in turnover rates were comparable whether the calculations were made from plasma or whole blood concentrations. At the end of surgery there was a high peripheral uptake of 3-hydroxybutyrate concomitant with a low release of amino acids.

Journal Article↗

PubMed1986

Origin and distribution of cerebral vascular innervation from superior cervical, trigeminal and spinal ganglia investigated with retrograde and anterograde WGA-HRP tracing in the rat.

Peripheral sources of cerebral vascular innervation have been investigated with retrograde and anterograde neuronal tracing of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) in the rat. For retrograde identification of sources of innervation, WGA-HRP was applied to the exposed basilar artery through a fine slit in the overlying meninges, and sections of brain and peripheral ganglia were reacted with tetramethylbenzidine for detection of the tracer. A high density of tetramethylbenzidine reaction product was observed around the basilar artery and in the surrounding pial tissue, but the application sites were not completely selective since some tracer always had spread into the ventral brain stem. Retrogradely labelled cell bodies were identified in the superior cervical, stellate, first and second spinal, and trigeminal ganglia, i.e. these ganglia may represent origins of basilar artery innervation. In a second series of experiments, microinjections of WGA-HRP were placed into the indicated ganglia to obtain anterograde labelling of nerve fibres on whole-mounts of the cerebral vessels. Injections into trigeminal ganglia labelled nerve fibres on the ipsilateral half of the circle of Willis, as well as the contralateral anterior cerebral artery and the rostral part of the basilar artery. The first and second spinal ganglia projected to the vertebrobasilar arteries, while the ipsilateral part of the internal carotid (outside the circle of Willis) received fibres from the second spinal ganglion. Nerve fibres originating in trigeminal and spinal ganglia were organised in bundles, and between these a sparse plexus of thin single fibres appeared. Injection of WGA-HRP into superior cervical ganglion labelled a plexus of nerve fibres on the ipsilateral circle of Willis and the (rostral) basilar artery. These experiments demonstrated the origin and distribution of sympathetic and sensory innervation to major cerebral arteries in the rat.

Animals↗

PubMed1986

The exchange of blood-borne amino acids in the leg during abdominal surgical trauma: effects of glucose infusion.

The exchange of plasma amino acids and glucose, lactate, glycerol and 3-hydroxybutyrate in the leg was studied in otherwise healthy patients undergoing elective cholecystectomy. Seven patients were given a constant intravenous infusion of glucose at a rate of 1.1 mmol/min throughout the study. Seven other patients who received normal saline only served as a control group. Measurement of leg blood flow and arterio-femoral venous differences of amino acids and other energy metabolites were made on four occasions: (I) before surgery, (II) 10 min after skin incision, (III) at the end of surgery, and (IV) 30 min after the end of anaesthesia. The release of amino acids from the leg was comparable in the two groups before and during the early part of surgery. At the end of surgery the release of several individual amino acids, as well as the total release of amino acids, from the leg was higher in the patients given glucose infusion compared with the control patients. The infusion of glucose prevented the intraoperative rise in arterial levels and uptake of 3-hydroxybutyrate in the leg. A high release of amino acids at the end of surgery was thus associated with low arterial levels of 3-hydroxybutyrate while the reverse pattern was seen in the control patients. These effects of glucose infusion were qualitatively different from those seen in uninjured postabsorptive man.

3-Hydroxybutyric Acid↗

PubMed1986

Effect of extradural analgesia on glucose metabolism and gluconeogenesis. Studies in association with upper abdominal surgery.

Concentrations of glucose and gluconeogenic substrates across the splanchnic circulation were studied in 20 patients undergoing cholecystectomy with general anaesthesia. In 10 patients, general anaesthesia was administered alone, and in 10 general anaesthesia was combined with thoracic extradural analgesia. All patients received a constant i.v. infusion of glucose. Blood glucose concentration increased markedly in the general anaesthesia group in contrast to a moderate and shortlived increase in the patients given extradural analgesia, in whom the splanchnic release of glucose tended to be lower. The splanchnic uptake of glycerol was lower in the patients given extradural analgesia, while the uptake of lactate and the increase in alanine uptake was similar in both groups. Plasma catecholamine and serum cortisol concentrations were higher in the group receiving general anaesthesia alone, while serum growth hormone concentration was higher after surgery in the extradural group. The addition of extradural blockade to general anaesthesia suppresses the increase in blood glucose concentration--and this may be related to a reduced splanchnic release of glucose combined with an increased peripheral uptake.

Abdomen↗

PubMed1986

Kinetics of carbon dioxide during cardiopulmonary resuscitation.

CO2 kinetics during CPR was investigated in 15 anesthetized piglets. BP, blood gases, and acid-base balance were monitored through catheters in the carotid artery and a central vein, as well as in cerebrospinal fluid. Cardiac arrest was induced by a transthoracic direct current shock. CPR was begun immediately by artificial ventilation and simultaneous external chest compressions. Epinephrine was administered after 8 min of CPR. One group (n = 5) of animals received no buffer treatment while another (n = 5) received an infusion of 75 mmol sodium bicarbonate and a third group (n = 5) received an equivalent amount of tris-buffer mixture. The results of these experiments, as well as previously described circulatory variables during CPR, were analyzed using a computer model describing the CO2 kinetics of the pig. Our main finding was that PaCO2 was positively correlated to cardiac output during CPR; improved cardiac output during CPR resulted in more efficient tissue CO2 elimination and was associated with increased survival rates. PaCO2 was also somewhat reduced by efficient alveolar hyperventilation. The arterial PCO2 and pH did not reflect the acid-base balance in peripheral tissues. During CPR, bicarbonate and tris-buffer mixture both quickly passed through the blood-brain barrier. When buffer treatment is indicated during CPR, a buffer which does not increase tissue PCO2 may be the drug of choice.

Acid-Base Equilibrium↗

PubMed1986

Pharmacokinetics of physostigmine after intravenous, intramuscular and subcutaneous administration in surgical patients.

The pharmacokinetics of physostigmine after intravenous, intramuscular or subcutaneous administration as well as its arousal effect after anaesthesia have been studied in surgical patients in the early postoperative period. After intravenous administration physostigmine had a very rapid plasma elimination with a plasma clearance ranging from 47 to 163 l/h with a mean +/- s.d. of 92.5 +/- 37.7 l/h. The volume of distribution was 46.5 +/- 19.2 l, while distribution and plasma elimination half-lives were 2.3 and 22 min, respectively. A fraction of the dose was probably hydrolyzed in blood since its blood elimination half-life in vitro was approximately 190 min. After both intramuscular and subcutaneous administration the systemic availability was almost complete, the plasma terminal half-lives only being somewhat longer than after intravenous administration. Plasma clearance, volume of distribution and elimination half-life of physostigmine were not correlated to age or body weight of the patients. The rapid plasma clearance of physostigmine resulted in a short duration of antisedative effect. After administration of 1 mg physostigmine salicylate i.v., drug-induced sedation was rapidly reversed with a duration of 30-60 min. The duration of action was similar after intramuscular injection but onset was delayed by 20-30 min. It was concluded that a plasma concentration of 3-5 ng/ml of physostigmine should be exceeded if an adequate analeptic effect is to be achieved, meaning that 2 mg of physostigmine had to be administered subcutaneously in order to achieve a satisfactory reversal of sedation. The short duration of action may hamper the use of physostigmine as an agent for reversal of drug-induced sedation and anticholinergic effects after surgery.

Adult↗

PubMed1986

A double-blind trial of the analgesic properties of physostigmine in postoperative patients.

A double-blind clinical trial of the analgesic and antisedative effects of physostigmine was carried out on surgical patients (n = 60) during the first hours postoperatively. Pethidine and placebo were included for comparison in the double-blind study. The degree of pain and sedation was estimated when the patient demanded analgesics and immediately before the administration of the test drug. The dosage administered i.v. was: physostigmine salicylate 2 mg, placebo = saline, or pethidine chloride 50 mg. After this, the same parameters were recorded at regular intervals. In addition, ventilatory rate, pulse rate, systolic blood pressure and side effects, if any, were noted. The results showed that physostigmine caused analgesia that was of the same magnitude as pethidine during the first 15 min, after which it decreased to the level of the placebo at 30 min. An antisedative or arousal effect was recorded over a somewhat longer time period; after this, there was no difference between placebo and physostigmine. In contrast to pethidine, physostigmine caused no decrease in the ventilatory rate. The pulse rate and systolic blood pressure did not change in any of the groups. Although the durations of the analgesic and antisedative effects of physostigmine were short, the use of this drug may well be preferable to the use of e.g. naloxone when immediate alertness of the patient is wanted without causing an increase in postoperative pain.

Adult↗

PubMed1986

A new nomogram facilitating adequate haemodilution.

When using deliberate haemodilution to a certain haematocrit value (Hct), the appropriate preoperative blood volume of the patient must be determined and matched with the transfusion volume at a certain blood loss. In order to facilitate such calculations a nomogram was constructed, aiming for a final Hct of 33%. Preoperative Hct, height, weight and sex of the patient are input variables. After drawing three straight lines, the nomogram yields the normal blood volume and the acceptable pre-transfusion blood loss (BL). This nomogram was used during surgery when the preoperative Hct exceeded 35%. Protocols from 100 patients bleeding more than 50% of their BL were studied. Blood loss was 1.1 +/- 0.6 1 (mean +/- s.d.) ranging from 0.4 to 4.0 1. Fifty-one of the patients received blood transfusion. This program resulted in a decrease of Hct (mean +/- s.d.) from 41 +/- 3% preoperatively to 33 +/- 4% during the first 30 min postoperatively. Sixty-three of the patients had a final Hct of 30-35%, 13 had 27-29% and one had 26%. The low values were most likely due to underestimation and consequent unsubstituted blood loss. In summary, the nomogram makes time-consuming mathematical operations unnecessary. It was easy to use and the postoperative Hct was close to that desired in most patients.

Adult↗

PubMed1986

Reversal of sedation and respiratory depression after anaesthesia by the combined use of physostigmine and naloxone in neurosurgical patients.

A clinical trial of the combination of naloxone in a low dose (1-1.5 micrograms X kg-1 body weight) with physostigmine (0.5-1.0 mg i.v.) was made to elucidate whether this combination could reverse postanaesthetic overdosing in neurosurgical patients without increasing postoperative pain. The investigation was made following previous findings that physostigmine has analgesic properties in addition to its systemic antisedative and anticholinergic effects as well as a stimulatory effect on morphine-depressed ventilation. Altogether 198 neurosurgical patients were investigated. The results showed that postanaesthetic over-sedation can be safely treated by a combination of naloxone and physostigmine in the dosages named above, resulting in the rapid reversal of sedation, where opiates, neuroleptics and benzodiazepines have been used. In contrast, this combination has very little effect on sedation following the administration of agents such as halothane and isoflurane. In the great majority of patients (95%), the treatment resulted in excellent analgesia during the first postoperative hour. The incidence of nausea and vomiting was increased somewhat by this treatment, but these side-effects could be minimized by decreasing the rate of drug administration. Physostigmine is contra-indicated in patients having symptoms and signs similar to those of Parkinson's disease, and the dose of physostigmine should also be reduced to 0.5 mg i.v. in all patients over the age of 65.

Adult↗

PubMed1986

A method for reliable and simultaneous cannulation of the epidural and subarachnoid spaces in pigs. A tool for the study of cerebrospinal fluid pharmacokinetics and drug penetration of the dura mater.

Many drugs are of interest from the point of view of their pharmacokinetical properties in the CSF, as well as their penetration of the dura mater after epidural application. A means of assessment of these properties is therefore of importance. The present report describes a method allowing reliable simultaneous cannulation of the epidural and subarachnoid spaces in the anaesthetized pig, with control of the catheter positions. The catheter tips can be placed at the same spinal level, separated only by the dura mater and arachnoid membrane. Both catheters are introduced via the atlanto-occipital membrane. We found this method a valuable tool in the research of drug disposition and other experimental procedures, where simultaneous and reliable access to the subarachnoid and epidural spaces is mandatory.

Animals↗

PubMed1986

The influence of abdominal surgery on the splanchnic exchange of amino acids.

The splanchnic exchange of amino acids was studied during and immediately after elective cholecystectomy in 10 patients given a constant infusion of glucose (1.1 mmol/min). Measurements of splanchnic blood flow and arteriohepatic venous differences of plasma amino acids, glucose, lactate and glycerol were made preoperatively, intraoperatively and twice in the immediate postoperative period. The arterial plasma concentration of most amino acids declined during and after surgery but the arterial concentration of alanine was highest in the postoperative period. The total splanchnic uptake of amino acids increased from 140.3 +/- 36.0 mumol/min preoperatively to 338.2 +/- 51.7 mumol/min postoperatively (p less than 0.05). Alanine and glutamine accounted for 65-70% of the total splanchnic uptake of amino acids throughout the investigation. The fractional extraction of methionine increased in the immediate postoperative period, while the fractional extraction of the remaining amino acids was stable. The splanchnic uptake of gluconeogenic substrates exceeded the splanchnic glucose release. The splanchnic uptake of amino acids had already increased intraoperatively and further increased postoperatively despite a net splanchnic glucose uptake in this period.

Abdomen↗

PubMed1985

Possible excitatory amino acid afferents to nucleus raphe dorsalis of the rat investigated with retrograde wheat germ agglutinin and D-[3H]aspartate tracing.

Evidence for excitatory amino acid afferents to nucleus raphe dorsalis (NRD) has been found with retrograde tracing techniques. For neuroanatomical definition of afferent sources to NRD, rats received stereotaxic injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) or implantations of crystal WGA-HRP in glass micropipettes. Retrogradely transported WGA-HRP was visualized with the tetramethyl-benzidine method, and afferents to NRD were identified from 20 different brain regions. Large numbers of labeled cells appeared in the lateral hypothalamus, lateral habenular nucleus, ventral tegmental area, periaqueductal gray, parabrachial nuclei and nucleus raphe magnus. Important inputs were also noted from dorsomedial hypothalamus and the area surrounding the perihypoglossal nucleus. Smaller numbers of WGA-HRP labeled cells appeared in bed nucleus of stria terminalis, diagonal band of Broca, cuneiform nucleus, superior vestibular nucleus, pontine periventricular gray, and some hypothalamic and reticular areas. Another group of rats received microinjections of D-[3H]aspartate (D[3H]Asp) and autoradiography consistently revealed retrograde labeling of cell bodies in 4 of the regions indicated by the WGA-HRP experiments as afferents to NRD. The most prominent aggregation of D-[3H]Asp-labeled cells was found in the lateral habenular nucleus, indicating that this input operates with an excitatory amino acid as transmitter. Significant numbers of D-[3H]Asp-labeled cells were also found in substantia nigra, periaqueductal and pontine periventricular gray. After large D-[3H]Asp injections involving NRD as well as surrounding areas, labeled cells were observed in several additional areas. Some of these areas were considered as afferents to surrounding periaqueductal gray or dorsal tegmental nuclei, while others may represent NRD afferents with relatively lower affinity for D-[3H]Asp. Several afferents to NRD failed to label with D-[3H]Asp, including diagonal band of Broca, hypothalamic areas, ventral tegmental area, parabrachial nuclei, locus coeruleus and reticular areas.

Amino Acids↗

PubMed1985

Post-operative substrate utilisation and gas exchange using two different TPN-systems: glucose versus fat.

Twenty patients were studied over the first 4 post-operative days following abdominal aortic surgery. Ten patients had 93% of their non-protein energy as glucose and insulin was given to keep blood glucose below 10 mmol/l. The other 10 patients had 80% of non-protein energy as fat (Intralipid). Amino acids corresponding to 12 g of nitrogen were given in both groups. Gas exchange, nitrogen balance, phosphate balance, vanillylmandelic acid (VMA) excretion, 1- and 3-methylhistidine in urine, acute phase proteins, immunoglobulins and albumin were followed. Substrate utilisation was calculated from indirect calorimetry data and nitrogen excretion. Metabolism in the early post-operative phase was found to adapt to the nutrition regimen given even though the composition was extreme either in fat or carbohydrate content. The glucose-insulin regimen had a better nitrogen sparing effect and based on the difference in 3-methylhistidine excretion it is suggested that mainly protein muscle benefitted from this. Regardless of the TPN-regimen given, those patients whose RQ deviated the most from the average in their group had the highest nitrogen excretion. The two groups showed no differences in plasma proteins and catecholamine excretion.

Journal Article↗

PubMed1985

Glucose balance and muscle glycogen during TPN in the early post-operative phase.

In order to study how muscle glycogen is influenced by different nutritional regimens in the early post-operative period we took muscle biopsies from 20 patients preoperatively and on the fourth post-operative day after abdominal aortic surgery. Ten patients received 93% of non-protein energy as glucose, 7% as fat (Intralipid) and insulin was given to keep the blood glucose below 10 mmol/l. The remaining patients had 80% of non-protein energy as fat (Intralipid). Amino acids constituting 12 g of nitrogen daily were given to both groups. Daily measurements of gas exchange (oxygen uptake, CO2-production) were performed and from these data glucose balance was calculated as the difference between glucose intake and glucose expenditure. Muscle biopsies were analysed for glycogen, adenosine triphosphate, glucose-6-phosphate, lactate and citrate. We found that it was possible to maintain muscle glycogen stores at pre-operative levels with a glucose-insulin regimen. With the fat regimen there was a 31% decrease in muscle glycogen and two patients had a negative glucose balance despite the fact that 150 g of glucose were given. Average glucose balance throughout the study correlated positively with glucose intake. A significant correlation between glucose on the third day and change in muscle glycogen content was found. Muscle content of adenosine triphosphate, glucose-6-phosphate, lactate and citrate were similar in both groups.

Journal Article↗

PubMed1985

Clinical buffering of metabolic acidosis: problems and a solution.

Traditionally sodium bicarbonate has been the buffer of first choice in the treatment of metabolic acidosis. This treatment, however, involves risks of developing a hyperosmolar state, a high sodium concentration in the blood, increased arterial carbon dioxide tension and, as a result of the latter, intracellular and intracerebral acidosis and also cerebral oedema. The buffering effect occurs slowly and as a consequence of this, and of the titration curve of sodium bicarbonate, overcorrection of metabolic acidosis is often seen. Tris buffer was introduced as an alternative and has been claimed to solve most of these problems, but on the other hand it entails a very high risk of peripheral venous thrombosis and thrombophlebitic lesions owing to its local irritative effect. In order to overcome these disadvantages a new mixture of Tris, acetate, bicarbonate and phosphate has been designed. In the studies described it was shown to have an adequate buffering effect and to provide a solution to most of the problems connected with buffering of metabolic acidosis. The new Tris buffer mixture has a buffering effect in blood equivalent to 0.5 mol/l sodium bicarbonate, although its sodium content has been decreased to one-third of pure sodium bicarbonate. Its administration also results in predictable buffering in cerebrospinal fluid and skeletal muscle. In a clinical study it was demonstrated that the new Tris buffer mixture results in sufficient and adequate buffering without significant side-effects.

Acetates↗

PubMed1985

Investigation of absorption, metabolism kinetics and DNA-binding of intratracheally administered benzo[a]pyrene in the isolated, perfused rat lung: a comparative study between microcrystalline and particulate adsorbed benzo[a]pyrene.

Benzo[a]pyrene (B[a]P) adsorbed onto urban air particles (UAP) or in microcrystalline form (MCr) was administered intratracheally to the isolated perfused lung in doses of 100 and 1.5 micrograms. The appearance rate constant calculated for B[a]P release to the perfusate buffer was significantly lower for B[a]P administered adsorbed onto UAP (0.007 +/- 0.002 min-1) compared to the microcrystalline preparation (0.051 +/- 0.030 min-1). A classical two-compartmental model fitted well to the elimination of B[a]P from the perfusate buffer, after administration in solution to the buffer reservoir; C = 24 e-0.05t + 14 e-0.01t (pmol/ml). The concentration of polar metabolites in the perfusion buffer, at the end of experiments was approx. 9-fold higher for lungs administered the microcrystalline preparation compared to UAP at 1.5 microgram doses. At the 100 microgram dose level, the difference between preparations was only 2-fold, the data indicating that enzyme saturation might be important at the high dose level. With regard to the metabolite pattern, adsorption of B[a]P onto urban air particles caused a relative increase in the formation of B[a]P-9,10-dihydrodiol, whereas the relative formation rate for phenols was decreased. The absolute levels of B[a]P metabolites covalently bound to DNA was significantly higher in lungs given the MCr preparation compared to the UAP. When calculated as the amount metabolites bound, in relation to the total amount polar metabolites at the end of perfusion, however, the UAP preparation was significantly more efficient to enhance the production of DNA binding metabolites; 2.62 +/- 0.59 X 10(-5) vs. 1.33 +/- 0.21 X 10(-5) (pmol covalently DNA-bound metabolites/mg DNA/pmol metabolites formed). The results indicate that urban air particles may exert a cocarcinogenic effect with polynuclear aromatic hydrocarbons by increasing the pulmonary residence time for the carcinogenic hydrocarbon and/or alter the metabolite pattern in a way that enhances the covalent binding of metabolites to DNA.

Animals↗

PubMed1985

Induction and treatment of metabolic acidosis: a study of pH changes in porcine skeletal muscle and cerebrospinal fluid.

Metabolic acidosis was induced in 18 piglets of Swedish native breed by prolonged iv infusion of lactic acid, which decreased both blood and muscle pH. A two- to three-fold increase in muscle lactate content was related to the decrease in muscle pH. Treatment of the induced metabolic acidosis with either sodium bicarbonate or a tris buffer mixture re-established normal or near-normal arterial pH, but PaCO2 remained elevated after sodium bicarbonate infusion. The pH in muscle and cerebrospinal fluid (CSF) normalized only in the group treated with the tris buffer mixture. Thus, the tris buffer mixture was more effective than traditional sodium bicarbonate in correcting the acid-base disturbance in the CSF and the muscle intracellular compartment.

Acidosis↗

PubMed1985

Effects of a thermal ceiling on postoperative hypothermia.

Moderate per- and postoperative hypothermia initiates an increased metabolism in the postoperative period. The subsequent demands on oxygen transport may be critical in poor risk patients. Nineteen healthy young women with moderate hypothermia after abdominal surgery were studied for 2 h postoperatively with or without external heating from a heating ceiling. Central and peripheral temperatures, oxygen consumption, plasma catecholamines and shivering were measured. A method for continuous measurement of oxygen consumption and carbon dioxide production during spontaneous breathing is described. The results suggest that postoperative external heating decreases oxygen consumption, shivering and plasma catecholamine levels. At the same time, the comfort of the patient is increased considerably.

Adult↗