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Biomedical subjects

L Wiklund

Publications and source records attributed to L Wiklund.

At least 19 recordsLinked to original sources
PubMed2006

Intracerebral administration of neuronal nitric oxide synthase antiserum attenuates traumatic brain injury-induced blood-brain barrier permeability, brain edema formation, and sensory motor disturbances in the rat.

The role of nitric oxide (NO) in traumatic brain injury (TBI)-induced sensory motor function and brain pathology was examined using intracerebral administration of neuronal nitric oxide synthase (nNOS) antiserum in a rat model. TBI was produced by a making a longitudinal incision into the right parietal cerebral cortex limited to the dorsal surface of the hippocampus. Focal TBI induces profound edematous swelling, extravasation of Evans blue dye, and up-regulation of nNOS in the injured cerebral cortex and the underlying subcortical areas at 5 hours. The traumatized animals exhibited pronounced sensory motor deficit, as seen using Rota-Rod and grid-walking tests. Intracerebral administration of nNOS antiserum (1 : 20) 5 minutes and 1 hour after TBI significantly attenuated brain edema formation, Evans blue leakage, and nNOS expression in the injured cortex and the underlying subcortical regions. The nNOS antiserum-treated rats showed improved sensory motor functions. However, administration of nNOS antiserum 2 hours after TBI did not influence these parameters significantly. These novel observations suggest that NO participates in blood-brain barrier disruption, edema formation, and sensory motor disturbances in the early phase of TBI, and that nNOS antiserum has some potential therapeutic value requiring additional investigation.

Animals↗
PubMed2006

Post-injury treatment with a new antioxidant compound H-290/51 attenuates spinal cord trauma-induced c-fos expression, motor dysfunction, edema formation, and cell injury in the rat.

The neuroprotective efficacy of post-injury treatment with the antioxidant compound H-290/51 (10, 30, and 60 minutes after trauma) on immediate early gene expression (c-fos), blood-spinal cord barrier (BSCB) permeability, edema formation, and motor dysfunction was examined in a rat model of spinal cord injury (SCI). SCI was produced by a longitudinal incision into the right dorsal horn of the T10-11 segment under Equithesin anesthesia. Focal SCI in control rats resulted in profound up-regulation of c-fos expression, BSCB dysfunction, edema formation, and cell damage in the adjacent T9 and T12 segments at 5 hours. Pronounced motor dysfunction was present at this time as assessed using the Tarlov scale and the inclined plane test. Treatment with H-290/51 (50 mg/kg, p.o.) 10 and 30 minutes after SCI (but not after 60 minutes) markedly attenuated c-fos expression and motor dysfunction. In these groups, BSCB permeability, edema formation, and cell injuries were mildly but significantly reduced. These observations suggest that (i) antioxidants are capable of attenuating cellular and molecular events following trauma, and (ii) have the capacity to induce neuroprotection and improve motor function if administered during the early phase of SCI, a novel finding.

Animals↗
PubMed2006

Neuroprotective effects of melanocortins in experimental spinal cord injury. An experimental study in the rat using topical application of compounds with varying affinity to melanocortin receptors.

The possibility that local administration of low molecular weight non-peptide compounds with varying affinities at melanocortin receptors in the spinal cord will influence pathophysiological outcome of spinal cord injury (SCI) was examined in a rat model. Five new Melacure compounds ME10092, ME10354, ME10393, ME10431 and ME10501 were used in this investigation. Each compound was dissolved in saline and tested at 3 different doses, i.e. 1 microg, 5 microg and 10 microg total dose in 10 microl applied topically 5 min after SCI. The animals were allowed to survive 5 h and trauma induced edema formation, breakdown of the blood-spinal cord barrier (BSCB) and cell injuries were examined and compared with untreated injured rats. A focal SCI inflicted by an incision into the right dorsal horn of the T10-11 segments resulted in marked edema formation, breakdown of the BSCB to Evans blue albumin and caused profound nerve cell injury in the T9 and the T12 segments. Topical application of ME10501 (a compound with high affinity at melanocortin, MC-4 receptors) in high doses (10 microg) resulted in most marked neuroprotection in the perifocal spinal cord (T9 and T12) segments. On the other hand, only a mild or no effect on spinal cord pathology was observed in the traumatized animals that received ME10092, ME10354, ME10393 and ME10431 at 3 different doses. These observations suggest that non-peptide compounds with varying affinity to melanocortin receptors are able to influence the pathophysiology of SCI. Furthermore, compounds acting at melanocortin, MCR4 receptors are capable to induce neuroprotection in spinal cord following trauma.

Administration, Topical↗
PubMed2006

Spinal cord injury induced heat shock protein expression is reduced by an antioxidant compound H-290/51. An experimental study using light and electron microscopy in the rat.

The possibility that oxidative stress participates in heat shock protein 72 kD (HSP 72) expression following a focal trauma to the spinal cord was examined using a potent antioxidant compound H-290/51 in a rat model. A focal spinal cord injury (SCI) inflicted by making a longitudinal incision on the right dorsal horn of the T10-T11 segment under equithesin anaesthesia resulted in profound upregulation of HSP 72 expression in the adjacent spinal cord segments T9 and T12. This expression of HSP was most marked in the ipsilateral cord at 5 h after SCI. Pretreatment with H-290/51 (50 mg/kg, p.o.) 30 min before SCI markedly attenuated HSP expression in the spinal cord seen at 5 h. The motor functions of traumatized rats were also improved in the drug treated group. At this time, structural changes in the spinal cord and edema formation were considerable reduced compared to the untreated traumatized rats. Taken together, these observations suggest that (i) oxidative stress participates in HSP response following trauma, and (ii) the antioxidant compound H-290/51 attenuates cellularstress, improves motor functions and induces considerable neuroprotection in the early phase of SCI. Further studies using post-injury treatment with H-290/51 is needed to explore its therapeutic potentials in clinical settings.

Animals↗
PubMed2006

Ammonium chloride and alpha-ketoglutaric acid increase glutamine availability in the early phase of induced acute metabolic acidosis.

BACKGROUND: Glutamine deficiency in critical illness is associated with increased morbidity and mortality. We hypothesized that ammonium chloride (NH(4)Cl) and alpha-ketoglutaric acid (alpha-KGA) infusions could increase glutamine availability possibly through de novo synthesis in the liver. METHODS: Anesthetized post-absorptive pigs were allocated to four groups (n = 8). The study groups received either a 4-h intravenous infusion of alpha-KGA, 11.4 micromol/kg/min and NH(4) (+), 9.7 micromol/kg/min (group 1), or alpha-KGA, 2.85 micromol/kg/min and NH(4) (+), 46.3 micromol/kg/min (group 2), or alpha-KGA, 11.4 micromol/kg/min (group 3), or isotonic saline (control group). Plasma concentrations of glutamine and glutamine exchange in liver, intestine and skeletal muscle were investigated. RESULTS: Plasma glutamine concentrations in group 1 (58% increase) were greater (P < 0.05) compared with the control group (14% decrease) and group 3 (13% decrease), and in group 2 (91% increase) compared with the control group, group 3 (P < 0.0001) and group 1 (P < 0.05). Intestinal glutamine extractions in group 2 were significantly greater (P < 0.01) compared with all other groups. Neither the liver nor the hind leg increased its release of glutamine. Arterial pH decreased (all P < 0.001) to 7.39 +/- 0.01 in the control group, 7.30 +/- 0.01 in group 1, 7.19 +/- 0.01 in group 2 and 7.35 +/- 0.01 in group 3. CONCLUSION: Infusions of alpha-KGA and NH(4)Cl, to a pH range of 7.20-7.30, did not enhance hind leg or hepatic glutamine release. The increased plasma concentrations of glutamine were effects of NH(4)Cl, not alpha-KGA, and caused either by de novo synthesis or decreased degradation.

Acidosis↗
PubMed2005

A new mechanical connector for distal coronary artery anastomoses in coronary artery bypass grafting: a randomized, controlled study.

OBJECTIVE: A new mechanical anastomotic device was evaluated, aiming at its future use in minimally invasive techniques or limited access surgery in patients undergoing coronary artery bypass grafting. METHODS: Between April and December 2002, a total of 60 patients scheduled for elective multivessel bypass grafting were randomly assigned. One vein graft-coronary artery anastomosis per patient was either performed with the St Jude Medical ATG coronary connector system (n = 30; St Jude Medical Inc, St Paul, Minn) or hand sewn (n = 30). Selective coronary angiography or coronary magnetic resonance imaging of the studied graft and vessel was included in the 6-month follow-up. RESULTS: Twenty-eight of the connectors were successfully implanted. Two patients were excluded from the study because of conversion to hand-sewn anastomoses. Six connector-made anastomoses were bleeding at the anastomotic site. At the time of follow-up (190 postoperative days), all control anastomoses and grafts were patent, whereas 26% of the connector anastomoses were occluded. One graft in each group was patent but with stenosis. CONCLUSION: The St Jude Medical ATG coronary connector system for distal anastomoses represents a new concept for sutureless anastomoses in cardiac surgery. This randomized, controlled study shows lower graft patency for anastomoses performed with the connector than for hand-sewn control anastomoses. It illustrates the importance of controlled studies when evaluating new technical equipment in medicine.

Adult↗
PubMed2005

Bridge to heart transplantation with the HeartMate device in Gothenburg, Sweden.

BACKGROUND: Patients rapidly deteriorating while waiting for heart transplantation present a major problem. Our strategy for this entity is the HeartMate left ventricular assist device (LVAD) VELVAS, an electrically driven implantable LVAD. Herein we report our initial experience. METHODS: The medical records of all the patients who received HeartMate LVAS at our institution were reviewed. RESULTS: From January 1997 through May 2004, 19 patients received a HeartMate. The mean age was 39 (15 to 61) years and 84% were men. The diagnoses were: dilated cardiomyopathy (n = 8), ischemic heart disease (n = 6), myocarditis (n = 3), congenital heart disease (n = 1), and hypertrophic cardiomyopathy (n = 1). Mean time on LVAD was 113 (10 to 353) days. Ten patients were discharged from the hospital to their homes awaiting transplant or recovery. Three patients showed recovery of heart function and were subsequently weaned from mechanical support. Thirteen patients underwent heart transplantation. Three patients died during LVAD treatment. Major adverse events occurred in nine patients, including severe right heart failure (n = 3), severe bleeding (n = 3), stroke (n = 1), hepatic failure (n = 1), and septicemia (n = 2). Nine of the 13 transplanted patients are alive and well today. CONCLUSION: HeartMate LVAS is a valuable option for patients rapidly deteriorating while awaiting a heart transplant. Our results are comparable with those reported from larger centers.

Adolescent↗
PubMed2003

Differences in cerebral reperfusion and oxidative injury after cardiac arrest in pigs.

BACKGROUND: An investigation of the free radical scavenger sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) and the weak vasodilatator Tris buffer mixture (TBM) on cerebral cortical blood flow (CCBF) and the jugular bulb concentration of two eicosanoids, indicators of oxidative stress and inflammation, was undertaken in 30 anaesthetized piglets during cardiopulmonary resuscitation (CPR) and after restoration of spontaneous circulation (ROSC). METHODS: Thirty animals were subjected to 8 min of untreated circulatory arrest followed by 8 min of closed-chest CPR. During CPR, the animals were randomized to receive 60 mg/kg S-PBN, 1 mmol/kg TBM or 2 ml/kg normal saline (n = 10 in each group). Systemic haemodynamic variables, CCBF and jugular bulb plasma concentrations of 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha were measured. RESULTS: The CCBF during reperfusion after ROSC was greater in the TBM group than in the S-PBN group, the regression coefficient between CCBF and mean arterial blood pressure being lower in the S-PBN group than in the TBM group. The jugular bulb plasma concentration of 8-iso-PGF2alpha during the first 30 min after ROSC was greater in the TBM group than in the S-PBN group. Administration of TBM after vasopressin did not attenuate the pressor effect of vasopressin. CONCLUSION: Administration of S-PBN during CPR results in less cerebral oxidative stress, possibly by promoting normal distribution of cerebral blood flow.

Animals↗
PubMed2002

The sevoflurane saving capacity of a new anaesthetic agent conserving device compared with a low flow circle system.

BACKGROUND: An anaesthetic agent conserving device (ACD) has been added to a Bain system to approach the agent-saving capacity of a low flow circle system. METHODS: Randomly selected ASA physical status I patients received a standardized anaesthetic with sevoflurane in air/O2 through either a circle system with 1.5 l/min fresh gas flow (n = 8), or through a Bain system with an added ACD with fresh gas flow 4.4-6.4 l/min (n = 8). A target controlled infusion of remifentanil was used for analgesia. RESULTS: The median sevoflurane consumption was 19.7 and 22.0 ml/MAC/h with the low flow circle system and the Bain system + ACD, respectively (P=0.10, Mann-Whitney U-test), or when adjusted for weight 0.25 and 0.28 ml/MAC/h/kg (P=0.26, Mann-Whitney U-test). CONCLUSION: The expenditure of sevoflurane with a Bain system + ACD was close to that in a circle system with 1.5 l/min fresh gas flow. It is thereby possible to use sevoflurane to all its potential, performing for example rapid alterations in end-tidal concentration using high fresh gas flows by combining a Bain system with an ACD. Although the price is not decided for this not yet commercially available device, a potential for a lower cost exists. Additionally, there will be no concerns of toxic compounds produced in the absorber.

Adult↗
PubMed2002

Neurological outcome after experimental cardiopulmonary resuscitation: a result of delayed and potentially treatable neuronal injury?

BACKGROUND: In experimental cardiopulmonary resuscitation (CPR) aortic balloon occlusion, vasopressin, and hypertonic saline dextran administration improve cerebral blood flow. Free radical scavenger alpha-phenyl-N-tert-butyl-nitrone (PBN) and cyclosporine-A (CsA) alleviate neuronal damage after global ischemia. Combining these treatments, we investigated neurological outcome after experimental cardiac arrest. METHODS: : Thirty anesthetized piglets, randomly allocated into three groups, were subjected to 8 min of ventricular fibrillation followed by 5 min of closed-chest CPR. The combined treatment (CT) group received all the above-mentioned modalities; group B was treated with balloon occlusion and epinephrine; and group C had sham balloon occlusion with epinephrine. Indicators of oxidative stress (8-iso-PGF(2 alpha)), inflammation (15-keto-dihydro-PGF(2 alpha)), energy crisis (hypoxanthine and xanthine), and anoxia/hypoxia (lactate) were monitored in jugular bulb venous blood. Neurological outcome was evaluated 24 h after CPR. RESULTS: : Restoration of spontaneous circulation (ROSC) was more rapidly achieved and neurological outcome was significantly better in the CT group, although there was no difference in coronary perfusion pressure between groups. The jugular venous PCO2 and cerebral oxygen extraction ratio were lower in the CT group at 5-15 min after ROSC. Jugular venous 8-iso-PGF(2 alpha) and hypoxanthine after ROSC were correlated to 24 h neurological outcome CONCLUSIONS: : A combination of cerebral blood flow promoting measures and administration of alpha-phenyl-N-tert-butyl-nitrone and cyclosporine-A improved 24 h neurological outcome after 8 min of experimental normothermic cardiac arrest, indicating an ongoing neuronal injury in the reperfusion phase.

Angioplasty, Balloon, Coronary↗
PubMed2002

Sigmoid colonic reflectance pulse oximetry and tonometry in a porcine experimental hypoperfusion shock model.

BACKGROUND: The objective of the present study was to determine if colonic endoluminal mucosal oxygen saturation, as determined by reflectance pulse oximetry, is an appropriate method to monitor colonic ischemia produced by a gradual partial constriction of the aorta in a porcine experimental model. METHODS: Piglets were anesthetized and mechanically ventilated. A Nellcor RS-10 reflectance pulse oximeter probe was attached to a Foley balloon catheter and passed transanally to record the oxygen saturation of the sigmoid colonic mucosa. For comparison, a tonometry catheter was introduced into the sigmoid colon. Hypoperfusion shock was induced by partial gradual constriction of the aorta. The same measurements but no intervention was performed in the control group. RESULTS: During one-third reduction of the aortic blood flow, the plethysmographic signal disappeared suddenly and the sigmoid colonic mucosa oxygen saturation (ScO2) measurements showed zero in seven out of the eight pigs. During two-thirds flow reduction, no plethysmographic signals were observed in any of the piglets. During the reperfusion period, ScO2 measurements with a good plethysmographic signal were obtained immediately after complete release of the aortic constriction in all pigs. Significantly decreased intramucosal pH and increased difference between the arterial and regional PCO2 (PCO2 gap) were observed during two-thirds blood flow reduction. CONCLUSION: In contrast to the results of previous investigations, the sigmoid colonic pulse oximetry was not useful because the method proved to be overly sensitive and non-linear in relation to regional blood flow.

Animals↗
PubMed2001

Intracellular hepatitis C virus RNA-dependent RNA polymerase activity.

Studies of intracellular hepatitis C virus (HCV) RNA-dependent RNA polymerase activity (RdRp activity) have been limited by the poor replicative capacity of HCV in cell culture. We have developed a method that allows for the measurement of HCV specific RdRp activity in eukaryotic cells. This method is based on the transient expression of the HCV polymerase and its templates under the control of the T7 promoter in the presence of an infection with recombinant vaccinia virus (vTF7-3) expressing the bacteriophage T7 DNA-dependent RNA polymerase. Both negative-strand and positive-strand RNA synthesis were characterised, and the role of the other HCV non-structural proteins for polymerase activity was assessed. With this assay we were able to show that: a) Intracellular HCV RdRp activity is not restricted to, but is higher for templates containing HCV specific sequences, b) The HCV polymerase is active within the polyprotein precursor, c) Cleavage of NS5b from the polyprotein precursor does not determine template specificity, and d) HCV RdRp activity is higher in the presence of the other HCV non-structural proteins and lower within a protease-deficient polyprotein precursor. This method allows the measurement of intracellular HCV polymerase activity and may be used to test substances against the HCV polymerase in search of potential drugs for anti-HCV therapy.

HeLa Cells↗
PubMed2001

Differences in the pharmacodynamics of epinephrine and vasopressin during and after experimental cardiopulmonary resuscitation.

Vasopressin has been investigated as a possible alternative to epinephrine during cardiopulmonary resuscitation (CPR). We tested the hypothesis that vasopressin, in comparison with epinephrine, would improve cerebral blood flow and metabolism during CPR as well as after restoration of spontaneous circulation (ROSC). A total of 22 anaesthetised piglets were subjected to 5 min of ventricular fibrillation followed by 8 min of closed-chest CPR. The piglets were randomly allocated to receive repeated boluses of either 45 microg/kg epinephrine or 0.4 U/kg vasopressin IV. Haemodynamic parameters, cerebral cortical blood flow and cerebral tissue pH and PCO(2) were continuously monitored during CPR and up to 4 h after ROSC. Cerebral oxygen extraction ratio was calculated. Cerebral cortical blood flow increased transiently after each bolus of epinephrine, while only the first bolus of vasopressin resulted in a sustained increase. The peak in cerebral cortical blood flow was reached approximately 30 s later with vasopressin. During the initial 5 min following ROSC, cerebral cortical blood flow was greater in the vasopressin group. In conclusion, there is a difference between epinephrine and vasopressin in the time from injection to maximal clinical response and the duration of their effect, but their overall effects on blood pressures and cerebral perfusion do not differ significantly during CPR. In contrast, vasopressin results in a greater cerebral cortical blood flow during a transient period after ROSC.

Adrenergic Agonists↗
PubMed2001

Cerebral ischaemia in experimental cardiopulmonary resuscitation--comparison of epinephrine and aortic occlusion.

The apparent inability of epinephrine to improve outcome after cardiopulmonary resuscitation (CPR) could be caused by direct negative effects on the cerebral circulation. Constant aortic occlusion with a balloon catheter could be an alternative way to improve coronary and cerebral perfusion during CPR. The objective of the present study was to compare the effects of standard-dose epinephrine with balloon occlusion of the descending aorta on cortical cerebral blood flow augmentation during CPR. Ventricular fibrillation was induced in 24 anaesthetised piglets. A non-intervention interval of 9 min was followed by open-chest CPR. The animals were randomised to receive repeated intravenous bolus doses of epinephrine 20 microg/kg or balloon occlusion of the descending aorta. Focal cortical cerebral blood flow was measured continuously using laser-Doppler flowmetry. Balloon occlusion of the aorta resulted in a significantly higher mean cortical cerebral blood flow and a lower cerebral oxygen extraction ratio than epinephrine during CPR. After restoration of spontaneous circulation the cerebral perfusion appeared compromised to the same extent in both groups, with lower blood flow compared to baseline, high cerebral oxygen extraction and cerebral tissue acidosis. No difference in cerebral cortical vascular resistance between the two groups could be detected. It is concluded that aortic balloon occlusion was superior to epinephrine in cerebral blood flow augmentation during resuscitation and did not generate adverse effects on cerebral blood flow, oxygenation or tissue pH after restoration of spontaneous circulation. No evidence of cerebral vasoconstriction induced by standard-dose epinephrine was found.

Animals↗
PubMed2001

Local 5,7-dihydroxytryptamine lesions of rat amygdala: release of punished drinking, unaffected plus-maze behavior and ethanol consumption.

Several serotonergic drugs are effective for anxiety disorders, but underlying mechanisms are unclear, and findings in experimental animals are difficult to reconcile with human data. It has been proposed that differential effects of serotonin within specific anatomical systems may account for these difficulties, and the amygdala has been suggested as one of the structures involved. To examine this hypothesis, the neurotoxin 5,7-dihydroxytryptamine was administered locally in rat amygdala. Within the amygdala, serotonin was depleted by approximately 80%, with other transmitters unaffected, and serotonin transporter labelling was decreased by approximately 85%. Cortical areas near the lesion site were also affected, although to a lesser degree. Other forebrain areas were unaffected. Lesions resulted in a specific anti-conflict effect in a punished drinking test, but did not influence elevated plus-maze behavior (under baseline conditions and after restraint stress), locomotor activity or ethanol intake. These data suggest that the punished drinking test and the elevated plus-maze may activate different components of fear circuitry, and that the serotonergic input to the amygdala specifically participates in fear-related behavioral suppression mediated by this structure.

5,7-Dihydroxytryptamine↗
PubMed2001

A new device to reduce the consumption of a halogenated anaesthetic agent.

We report the first clinical application of a new anaesthetic agent-saving device. The principles of a heat-moisture exchanger have been further developed to create a device that reduces inhalational agent consumption. Sixteen patients were randomly allocated to receive isoflurane through either a vaporiser or through the agent-saving device. A coaxial Mapleson D system (Bain) was used in both groups. A standard ventilatory setting was used, aiming for normocapnia. Mean (SD) isoflurane consumption was 24.5 (2.8) ml x MAC-hour(-1) with the vaporiser, compared with 15.2 (3.0) ml x MAC-hour(-1) with the new device (p < 0.05). This corresponded to a 40% saving in the consumption of isoflurane. The amount of isoflurane that was scavenged to the atmosphere was reduced by an average of 55%.

Adult↗
PubMed2001

Incidence and geographical distribution of sudden infant death syndrome in relation to content of nitrate in drinking water and groundwater levels.

BACKGROUND: Previous studies indicate that the enteral bacterial urease is inhibited in victims of sudden infant death syndrome (SIDS). One possible inhibitor of this bacterial activity is nitrate. If ambient pollution by nitrate is involved in the etiology of SIDS only a fraction of the nitrate concentration not infrequently found in drinking water would be enough for this inhibition. METHODS: Occurrence of SIDS (n = 636) in Sweden during the period 1990 through 1996 were analysed regarding geographical and seasonal distribution in relation to the nitrate concentration in drinking water and changes in the groundwater level. RESULTS: Both the birth rate and the incidence of SIDS decreased during the study period. One quarter of the municipalities constituting 11% of the population had no cases, the maximum incidence being 6.5 per 1000 live births. Seasonality: The northernmost parts of the country had its highest incidence when the rest of the country had its lowest incidence, and the occurrence of individual deaths was associated with the recharge of groundwater which increases its nitrate content. The local incidence of SIDS was correlated (rs = 0.34-0.87) to maximally recorded concentrations of nitrate in drinking water. CONCLUSIONS: The seasonal distribution of SIDS was widely different from the south to the north of the country and seems to be associated with differences in the groundwater level changes subsequent to precipitation, frost penetration, and melting of snow. Use of drinking water with high peak concentrations or great variations in nitrate concentration was correlated to the incidence of SIDS.

Humans↗