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Biomedical subjects

L Wiklund

Publications and source records attributed to L Wiklund.

At least 127 records · Page 7Linked to original sources
PubMed1989

The biological activity of adrenaline after injection through an intravenous cannula containing alkaline buffer.

Since it is known that alkaline pH inactivates adrenaline it has been recommended that this drug not be administered in the same i.v. line as alkaline buffer solutions during cardiopulmonary resuscitation. In order to test the validity of this statement a simulation model of the clinical situation was designed where the biological activity of adrenaline was measured in anesthetized rats after having been mixed with alkaline buffer solution contained in a standard i.v. cannula. The biological activity of adrenaline was measured by comparing the blood pressure response after repeated administration of a test (adrenaline + alkaline buffer) and control (adrenaline + normal saline) solution to a rat which had previously received a ganglion-blocking agent. Two alkaline buffer solutions, sodium bicarbonate and Tris buffer mixture were tested. These resulted in a decrease of the biological effect of adrenaline to 77 +/- 6 and 82 +/- 9% of control values, respectively. If however, adrenaline mixed with Tris buffer mixture was injected into a recipient of phosphate buffer (pH 7.40 and buffer capacity equal to human blood) as much as 94 +/- 17% of its activity remained. The results lead us to suggest that, in the cardiopulmonary resuscitation situation, adrenaline may well be given via a cannula containing alkaline buffer solution without significant interference with its effect.

Animals↗
PubMed1989

Reversal of postoperative somnolence using a two-rate infusion of physostigmine.

In order to antagonize immediate postoperative somnolence, 24 surgical patients were given a two-rate infusion of physostigmine, aiming at a constant plasma concentration in the range of 1 to 10 ng/ml. Plasma concentrations of physostigmine were determined during infusion and after infusion and the effects of physostigmine on analgesia and postoperative sedation, and its side effects were monitored throughout. On the 1st postoperative day some of the patients (n = 8) were given 5 mg physostigmine orally, after which plasma concentrations as well as effects were measured. Steady-state concentrations were generally lower than predicted. Clearance varied between 10 and 85 ml/min x kg with a mean of 40.8 +/- 21.0 ml/min x kg. Oral bioavailability was 25.3 +/- 11.1%. Physostigmine administered as an intravenous infusion antagonized immediate postoperative somnolence in 21 out of 24 patients. Effects were poorly correlated with the established steady-state concentration of physostigmine. The patients' experience of postoperative pain relief was mostly satisfactory and the side effects of physostigmine infusion were generally limited. The effects of physostigmine in the immediate postoperative period seemed dependent on the dose as well as on the time which had elapsed since administration of anticholinergic drugs. After oral physostigmine administration the following morning, the majority of patients experienced side effects such as nausea and abdominal pain. In conclusion, physostigmine given as infusion antagonizes postoperative somnolence. However, the arousal effect was considered not better than that resulting from a bolus dose of the drug, although the infusion regimen allowed a prolonged clinical effect duration.

Administration, Oral↗
PubMed1988

Autoradiographic and electrophysiological evidence for excitatory amino acid transmission in the periaqueductal gray projection to nucleus raphe magnus in the rat.

Selective retrograde labelling was used as an autoradiographic method to identify possible excitatory amino acid afferents to nucleus raphe magnus (NRM). Injections of 25-50 nl 10(-2) or 10(-3) M D-[3H]aspartate into the NRM resulted in prominent labelling of cells in ventrolateral mesencephalic periaqueductal gray (PAG). Electrophysiologically, stimulation in ventrolateral PAG excited cells in NRM with a latency of 2-12 ms. With many cells, microelectrophoretic application of the excitatory amino acid antagonists, kynurenate and gamma-D-glutamyl-glycine, resulted in a reversible reduction of the PAG-evoked response. Selective antagonists of N-methyl-D-aspartate (NMDA) were less effective. It is suggested that neurones in the ventrolateral PAG projecting to NRM utilize an excitatory amino acid or structurally related compound as a transmitter, and that this transmitter acts on receptors of the non-NMDA type.

Amino Acids↗
PubMed1988

Stellate ganglion innervation of the vertebro-basilar arterial system demonstrated in the rat with anterograde and retrograde WGA-HRP tracing.

Stellate ganglia projections to cerebral arteries have been investigated with wheatgerm-agglutinated horseradish peroxidase (WGA-HRP). Injections of WGA-HRP into the stellate ganglia resulted in labelling of nerve fibres on the vertebral and basilar arteries, and their side branches. The innervation was bilateral, but with an ipsilateral predominance. After WGA-HRP application on the basilar artery, retrogradely labelled cells appeared in both stellate ganglia, but most numerously in the right ganglion (70-75%). Failure to detect stellate projections to cerebral arteries in 6-hydroxydopamine (6-OHDA)-pretreated animals indicates that these fibres are of noradrenergic sympathetic character. It is suggested that the stellate fibres follow the vertebral arteries towards the basilar artery and its branches.

Afferent Pathways↗
PubMed1988

Brain stem terminations of the trigeminal and upper spinal ganglia innervation of the cerebrovascular system: WGA-HRP transganglionic study.

The central projections of the nerve fibers innervating the middle cerebral and basilar arteries were investigated by transganglionic tracing of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) in the rat. WGA-HRP was applied to the exposed basilar and/or middle cerebral arteries. Sections of the brain, trigeminal and upper spinal ganglia were reacted with tetramethylbenzidine for detection of the tracer. The results demonstrate that trigeminal neurons that innervate the middle cerebral artery project to the trigeminal main sensory nucleus, pars oralis, and the dorsocaudal two-fifths of pars interpolaris of the trigeminal brain stem nuclear complex. Terminals were also visible in the ipsilateral nucleus motorius dorsalis nervi vagi (dmnX) and in the lateral nucleus tractus solitarius (nTs) bilaterally at the level of the obex. The ventral periaqueductal gray, including the dorsal raphe and C2 dorsal horn, were also innervated by nerve fibers from the middle cerebral artery. Ipsilateral trigeminal rhizotomy prior to WGA-HRP application over the middle cerebral artery impeded the visualization of nerve terminations throughout the brain stem. Pretreatment with capsaicin reduced the density of labeled neurons and terminals within the trigeminal ganglion and the brain stem, respectively, following WGA-HRP application over the middle cerebral artery. Basilar artery fibers terminate in the C2 dorsal horn, the cuneate nuclei, dmnX, and nTs bilaterally. A few projections were also labeled in the ventral periaqueductal gray. Unilateral upper two spinal dorsal rhizotomy prior to WGA-HRP application over the exposed basilar artery resulted in terminal labeling within the C2 dorsal horn, the cuneate nucleus, dmnX, and nTs contralateral to the rhizotomy, whereas the ipsilateral side was devoid of any labeling. Bilateral superior cervical ganglionectomy prior to WGA-HRP administration to the middle cerebral and basilar arteries did not alter the visualization of nerve terminations throughout the brain stem.

Animals↗
PubMed1988

Pulmonary disposition of pethidine in postoperative patients.

1. Two methods of pethidine administration, namely constant-rate infusion and single i.v. injection, were used to assess the pulmonary disposition of the drug in 10 postoperative patients. Using two sites of blood sampling, the pulmonary extraction ratio was determined. 2. Pronounced pulmonary uptake of pethidine was found in all patients (n = 10). On the other hand, there was no significant evidence of pulmonary clearance. 3. The mean total plasma clearance was 810 ml min-1 and the volume of distribution was 3.11 kg-1. 4. A flow model was used to describe the disposition of pethidine in man. The concentration-time profiles calculated by the model were in accordance with observed data. The data showed that both pulmonary uptake and pulmonary release of pethidine were rapid. 5. Constant-rate infusion was found advantageous in the determination of pulmonary extraction, with respect to the accuracy and precision of the results. The extraction obtained after a single injection may be overestimated on account of uptake of the drug by the lungs.

Aged↗
PubMed1988

Pulmonary complications after upper abdominal surgery: their prevention with intercostal blocks.

A prospective study of postoperative pulmonary complications (PPC) appearing during the hospital stay was carried out in 417 patients undergoing surgery through a subcostal or midline incision. Postoperative pain was relieved either by intercostal block and centrally-acting analgesics on demand or by centrally-acting analgesics alone. Pulmonary complications were diagnosed from combined physical and radiological signs. After biliary surgery through a subcostal incision, PPC were less frequent (P less than 0.05) in patients receiving intercostal blocks (6%) than in those given centrally-acting analgesics (11%). After surgery through a midline incision, the complication rate was higher, 15-57%, and was related to the type of surgery, the highest incidence being found after partial gastrectomy and operations for malignancy, and no significant reduction in the rate of PPC after intercostal blocks with this incision was found in any age group. Indeed, an increased rate of PPC was found in our patients over the age of 60 who had received bilateral intercostal blocks. Irrespective of the type of incision, surgery or method of postoperative pain relief, the patients with PPC more often had respiratory or other disorders preoperatively or a surgical complication intra- or postoperatively than those with normal postoperative recovery. Predisposing physical factors and high age were more common among the patients developing PPC in spite of treatment with intercostal blocks compared to those without such treatment.

Abdomen↗
PubMed1987

Selective retrograde labeling with D-[3H]-aspartate in the monkey olivocerebellar projection.

The specificity of D-[3H]-aspartate as a retrograde marker was investigated following large injections of this tritiated amino acid in the monkey cerebellar cortex. Retrogradely labeled neurons were found exclusively in the inferior olive, a fact which is consistent with previous studies in the rat. These results show that D-[3H]-aspartate is a selective tracer that might also be useful to delineate excitatory pathways using glutamate and/or aspartate as neurotransmitter(s) in the monkey brain.

Animals↗
PubMed1987

Innervation and reinnervation of rat inferior olive by neurons containing serotonin and substance P: an immunohistochemical study after 5,6-dihydroxytryptamine lesioning.

Serotonin (5-HT) and substance P (SP) immunoreactive axon terminals were visualized in the inferior olivary complex (IOC) of adult rats, 1 to 2 weeks or 6 to 12 months after cerebro-ventricular injection of 5,6-dihydroxytryptamine (5,6-DHT). In normal or saline-injected controls of the same age, there was some overlap between the respective distributions of 5-HT- and SP-immunostained axonal varicosities among the various subdivisions of IOC. At short time intervals after the 5-HT axotomy, almost as many degenerating axonal profiles showed immunoreactivity to SP as to 5-HT throughout the IOC, suggesting the coexistence of both transmitters within the same fibres. A few areas continued to exhibit characteristic patches of 'normal-looking' SP immunoreactivity, consistent with a distinct innervation by SP fibres without coexistent 5-HT. At prolonged survival times after 5,6-DHT treatment, there was a massive increase in the number-and striking similarity in the distribution-of IOC axonal varicosities immunostained for SP as well as for 5-HT. This neo-innervation involved certain subdivisions of the IOC normally receiving fibres of either type (e.g. dorsal accessory olive), but also others normally poor in 5-HT and/or SP (e.g. medial accessory olive). It remains to be determined if this abundance of 5-HT-SP terminals in the 'hyperinnervated' IOC reflected a particular capacity to express both transmitters in regenerating 5-HT neurons.

5,6-Dihydroxytryptamine↗
PubMed1987

Carbon dioxide production during mechanical ventilation.

Because of large stores of CO2 in different body tissues, metabolic change cannot be detected by measuring gas exchange until the CO2 stores have adapted to the new situation. Similarly, changes in the CO2 stores not due to metabolic alterations, may lead to error in gas exchange measurements. We studied CO2 production (VCO2) and oxygen consumption (VO2) in mechanically ventilated ICU patients, where CO2 stores were altered by: a) changing minute ventilation by 15%, b) reducing body temperature, and c) changing the level of sedation. Expired gases went through a mixing chamber and were analyzed continuously by a mass spectrometer. Signals from this instrument, together with gas-volume signals from the ventilator, were fed to a computer for calculation of VO2 and VCO2. Twenty to 120 min were required to reach a stable level, depending on the patient's size and circulatory response. Similar results were obtained by computer simulation using a five-compartment model of CO2 stores. These experiments indicate that measuring VO2 (for calculation of metabolic respiratory quotient [RQ]) in ventilated patients should occur after the patients maintain a 60-min period of stable body temperature and awareness. Ventilatory variables should not be changed substantially during the 90-min period before gas sampling. Cardiac output and muscle blood flow should not have changed 2 to 3 h before measuring RQ. If muscle blood flow is low, the stable periods for body temperature and ventilatory variables should be increased.

Carbon Dioxide↗
PubMed1987

Circulatory effects of short-term hypercapnia during thoracolumbar epidural anaesthesia.

In ten elderly patients subjected to extensive thoracolumbar epidural anaesthesia, circulatory changes were studied before and during sympathetic stimulation. Induced hypercapnia was used as a sympathetic stimulus. After establishment of the epidural anaesthesia, which extended from T1 to L2, there were decreases in heart rate, mean arterial blood pressure, cardiac output and systemic vascular resistance. Hypercapnia before the epidural block increased heart rate, arterial blood pressure and cardiac output, while hypercapnia after established epidural block induced only a slight increase in arterial blood pressure. The results indicate that in spite of an extensive epidural block, there are some "escaped" sympathetic nerve fibres that can be mobilized during sympathetic stimulation.

Aged↗
PubMed1987

Haemodynamic effects of intravenous bupivacaine during high thoracic epidural anaesthesia.

Administration of small doses of bupivacaine epidurally at the upper thoracic level will partially block the cardiac sympathetic nerves but not the sympathetic outflow via the adrenals. Local anaesthetics have direct systemic effects on the myocardium and the systemic circulation. The present study aimed to examine the effect of high thoracic epidural anaesthesia (TEA) in elderly patients, and to examine the effect of raising plasma bupivacaine concentrations in these patients, who had earlier had the sympathetic innervation of the heart blocked by thoracic epidural anaesthesia. Fifteen elderly patients scheduled for thoracotomy took part in the study. All received high thoracic epidural anaesthesia including the upper five thoracic dermatomes. When epidural block was established, ten patients received bupivacaine 3 mg/min intravenously for 20 min, while five patients received a corresponding volume of normal saline solution. After TEA was established, heart rate, mean arterial blood pressure and cardiac output decreased. When bupivacaine was given to these patients intravenously during the block, mean arterial blood pressure increased, while cardiac output decreased still more. The mechanisms behind these effects seem to be a direct constriction of the systemic blood vessels and a depressive effect on the myocardium, which was blocked from the influence of the cardiac sympathetic nerves by the high thoracic epidural block.

Aged↗
PubMed1987

The influence of epidural analgesia on the splanchnic exchange of amino acids during upper abdominal surgery.

Splanchnic turnover of plasma amino acids was studied in 10 patients given thoracic epidural analgesia combined with general anaesthesia for elective cholecystectomy. Ten other patients given only general anaesthesia for cholecystectomy served as a control group. All patients received an infusion of glucose during the investigation. The total concentration of amino acids in arterial plasma did not change in the patients given epidural analgesia but decreased by approximately 15% in the non-epidural group. In both groups splanchnic uptake of amino acids increased during surgery and was found to be more than doubled in the early postoperative period. The addition of epidural analgesia to general anaesthesia did not modify the splanchnic uptake of amino acids during surgery and in the immediate (2 h) postoperative period.

Abdomen↗
PubMed1986

Further evidence for excitatory amino acid transmission in the lateral habenular projection to the rostral raphe nuclei: lesion-induced decrease of high affinity glutamate uptake.

In previous autoradiographic studies we reported selective retrograde D-[3H]aspartate labelling of lateral habenular afferents to the nuclei raphe dorsalis (NRD) and centralis superior (RCS). This study reports biochemical support, lesion-induced decrease of high affinity glutamate uptake, for excitatory amino acid transmission in the habenulo-raphe connection. Rats received bilateral electrolytic lesions in the lateral habenular nuclei and survived 9-10 days. Brainstems were sectioned on a Vibratome, and NRD and RCS tissue microdissected. Glutamate uptake in sham-operated rats was in the NRD 23.6 +/- 2.3 nmol/g prot. (mean +/- S.E.M.) ([3H]glutamate 10(-7) M, 3 min, 25 degrees C) and in the RCS 14.6 +/- 1.0 nmol/g. Habenular lesions reduced glutamate uptake in the NRD by 20.7 +/- 2.0% (P less than 0.001) and in the RCS by 10.7 +/- 4.3% (P less than 0.05).

Amino Acids↗
PubMed1986

Afferent and efferent connections of striatal grafts implanted into the ibotenic acid lesioned neostriatum in adult rats.

The afferent and efferent connections of grafts of fetal caudate-putamen, implanted into the ibotenic acid (IA)-lesioned striatum of adult rats, have been studied with wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) as a combined retrograde and anterograde tracer, and with aldehyde fluorescence histochemistry for the visualisation of dopamine-containing nigrostriatal afferents from the host. The WGA-HRP was deposited in crystalline form (within a capillary tip) either into the depth of the graft tissue, or into the IA lesioned host striatum as a control. Labelling was only evaluated in specimens where the WGA-HRP deposit was entirely confined within the graft. Retrogradely labelled neurons were most consistently found in the ipsilateral host substantia nigra and the spared portions of the host CP, and in one case also in the midline and intralaminar thalamic nuclei normally projecting to the striatum. Some neurons, although weakly labelled, occurred in the deep layers of the frontal cortex in all grafted rats. Signs of anterograde WGA-HRP labelling in the host were found in one of the five animals in the ipsilateral globus pallidus and substantia nigra, pars reticulata. Fluorescence histochemistry revealed extensive ingrowth of dopamine-containing fibres from the host striatum into the grafted striatal tissue. The ingrowing fibres formed distinct and partly interconnected patches, most prominently in the peripheral regions of the grafts. The results provide evidence that intrastriatal grafts of fetal striatal tissue receive extensive dopaminergic afferents from the host substantia nigra, and that they may be capable of establishing connections also with thalamus, neocortex and globus pallidus of the host, as well as with the spared portions of the host caudate-putamen. The afferent connections from the thalamus and neocortex were notably more variable and sparse. However, since the control WGA-HRP deposits (into the lesioned host striatum) labelled the cortical and thalamic afferent neurons only poorly, it appears that the cortico-striatal and thalamo-striatal afferents (in contrast to the nigro-striatal ones) had undergone substantial degenerative changes (atrophy and/or cell death) in the long-term (6-11 months) IA-lesioned rats. The sparse thalamic and cortical afferent connections to the grafts may thus reflect an inability of the grafted striatal tissue to prevent the course of degenerative changes in these striatal input systems.

Animals↗
PubMed1986

Potential pulmonary uptake and clearance of morphine in postoperative patients.

The influence of lung uptake and lung clearance on the disposition of morphine was studied in surgical patients. In the postoperative period morphine was given intravenously by a two-rate infusion regimen. Under steady-state conditions samples of mixed central venous blood (pulmonary artery) and peripheral arterial blood (radial artery) were taken simultaneously and at the same time cardiac output was measured. The concentration differences between venous and arterial blood were used to calculate the extraction ratio of morphine across the lung. In all patients there was marked pulmonary uptake, but the concentration differences in most of them were small under steady-state conditions. The extraction ratio (mean +/- SD) across the lung was 0.06 +/- 0.10, implying insignificant lung clearance. However, in two patients, both with diabetes mellitus, there was a significant concentration gradient, indicating that the lung could contribute to the total body elimination of morphine. On the other hand, the total clearance was similar in diabetic and nondiabetic patients (1190 and 1150 ml/min, respectively), implying that pulmonary clearance would have no significant influence on the kinetics of morphine. A physiologically based pharmacokinetic model was used to describe the disposition of morphine in post-operative patients. The model allowed simulation of pulmonary diffusion, uptake and elimination and supported conclusions based on model-independent experimental data.

Adult↗