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Biomedical subjects

L Wiklund

Publications and source records attributed to L Wiklund.

At least 55 records · Page 3Linked to original sources
PubMed2000

Adverse effects of high-dose epinephrine on cerebral blood flow during experimental cardiopulmonary resuscitation.

OBJECTIVE: To study the effects of high-dose epinephrine, compared with standard-dose epinephrine, on the dynamics of superficial cortical cerebral blood flow as well as global cerebral oxygenation during experimental cardiopulmonary resuscitation. We hypothesized that high-dose epinephrine might be unable to improve cerebral blood flow during cardiopulmonary resuscitation as compared with standard-dose epinephrine. DESIGN: Randomized controlled study. SETTING: University hospital research laboratory. SUBJECTS: A total of 20 male anesthetized piglets. INTERVENTIONS: Ventricular fibrillation was induced. A nonintervention interval of 8 mins was followed by open-chest cardiopulmonary resuscitation. The animals were randomized to receive repeated bolus injections of either 20 microg/kg (standard-dose group, n = 10) or 200 microg/kg (high-dose group, n = 10) of epinephrine. MEASUREMENTS AND MAIN RESULTS: Focal cortical cerebral blood flow was measured continuously by using laser Doppler flowmetry. The duration of blood flow increase was significantly shorter in the high-dose group after the second dose of epinephrine. In the high-dose group there was also a consistent tendency for lower peak levels and shorter duration of flow increase in response to repeated bolus doses of epinephrine. Cerebral oxygen extraction ratio was significantly lower in the high-dose group after administration of epinephrine. CONCLUSIONS: Repeated bolus doses of epinephrine 200 microg/kg, as compared with 20 microg/kg, do not improve superficial cortical cerebral blood flow during experimental open-chest cardiopulmonary resuscitation. High-dose epinephrine appears to induce vasoconstriction of cortical cerebral blood vessels resulting in redistribution of blood flow from superficial cortex. This might be one explanation for the failure of high-dose epinephrine to improve overall outcome in clinical trials.

Animals↗
PubMed2000

Children with septo-optic dysplasia - how to improve and sharpen the diagnosis.

The data in this article are based on investigations performed in 25 children with suspected septo-optic dysplasia (SOD). There are many signs and methods that help in the diagnosis of SOD. In particular, the ocular fundus, abnormalities of the hypothalamo-pituitary axis and other midline brain structures should be described. In order to achieve a more holistic and functional diagnosis, the degree of neurological, neuropsychiatric and psychological involvement should also be stated. It has been suggested that SOD is associated with autosomal recessive inheritance, and it can be speculated that it is the result of genetic and environmental influences early in gestation. An early diagnosis can favourably influence the outcome of the affected child.

Blindness↗
PubMed1999

[Bypass surgery on beating heart without heart-lung machine. A new technique revitalises an old method].

Recently, new methodology entailing limited anterior thoracotomy or median sternotomy has rendered coronary surgery on the beating heart without extracorporeal circulation safe. Since a program for CABG on beating heart was initiated at Sahlgrenska University Hospital three years ago, 350 operations have been performed, 287 via sternotomy and 63 via limited thoracotomy. Mortality was 1.4% while graft patency in the first 84 patients was 94%. About 20% of all CABG's are performed on a beating heart, and signs are that this percentage is on the rise.

Coronary Artery Bypass↗
PubMed1999

Maximisation of cerebral blood flow during experimental cardiopulmonary resuscitation does not ameliorate post-resuscitation hypoperfusion.

Continuous intra-aortic balloon occlusion has been reported to improve cerebral blood flow during cardiopulmonary resuscitation (CPR) but not to ameliorate the impaired blood recirculation occurring after restoration of spontaneous circulation (ROSC). Volume expansion with hypertonic solutions may improve recovery of brain function by enhancing post-resuscitation cerebral blood flow. We hypothesised that the combination of these treatments with open-chest CPR would improve cerebral blood flow during CPR, and attenuate post-resuscitation flow disturbances. In 32 anaesthetised piglets, catheters were placed for haemodynamic and blood gas monitoring. Open-chest CPR was initiated after 9 min of ventricular fibrillation. The piglets were treated either with 3 ml kg(-1) hypertonic saline and dextran (HSD) (n = 10), HSD and balloon occlusion (n = 10) or with normal saline (n = 12). After 7 min of CPR, internal defibrillatory shocks were administered to restore spontaneous circulation. Haemodynamic variables, continuous cerebral cortical blood flow, cerebral tissue pH and pCO2 and blood gas parameters were measured during CPR and up to 210 min after ROSC. Higher cerebral perfusion pressure was found in the balloon-HSD group during CPR. This group exhibited less arterial hypertension immediately after ROSC compared with the other groups. Thereafter, a fairly rapid decrease of the perfusion pressures was observed in all groups reaching a minimum level approximately 30 min after ROSC. Cerebral cortical blood flow was significantly higher and cerebral oxygen extraction ratio significantly lower in the balloon-HSD group during CPR, but not after ROSC. In conclusion, a combination of intra-aortic balloon occlusion and HSD administration improves cerebral blood flow and brain oxygen supply during experimental open-chest CPR. In contrast, cerebral blood flow after ROSC was not shown to be influenced by this treatment.

Animals↗
PubMed1999

Intraperitoneal and sigmoid colon tonometry in porcine hypoperfusion and endotoxin shock models.

BACKGROUND: The objective of the present study was to assess the accuracy of an air tonometry device in vivo within a wide range of regional carbon dioxide tension (PrCO2) values by using saline tonometry as the standard and to investigate the possibilities to monitor perfusion of the intestine by tonometry in the intraperitoneal cavity. METHODS: Piglets were anesthetized and mechanically ventilated. A pair of tonometry catheters was placed in the sigmoid colon, while another pair was placed intraperitoneally in the right lower quadrant of the abdomen. Air tonometric regional PCO2 (aPrCO2) was measured every 15 min intraperitoneally and every 20 min in the sigmoid colon. Saline tonometric measurements were made every 30 min and steady-state values (ssPrCO2) were derived. Hypoperfusion shock was induced by graded constriction of the aorta. Endotoxin shock was induced by administration of lipopolysaccharide (LPS). RESULTS: The obtained average PrCO2 (=matched (aPrCO2+ ssPrCO2)/2) values ranged from 5.1 kPa to 14.7 kPa. Regional air PCO2 (aPrCO2) and steady-state saline PCO2 (ssPrCO2) exhibited a strong positive linear relationship (r=0.959). The 95% confidence interval of the mean of dPrCO2 (=aPrCO2-ssPrCO2) was 0.31-0.46 kPa. Intraperitoneal tonometric PrCO2 was lower than intraluminal PrCO2 in the sigmoid colon, and was also more sensitive to circulatory changes than sigmoid colon PrCO2. CONCLUSION: The regional air PCO2 (aPrCO2) showed good agreement with the steady-state saline regional PCO2 (ssPrCO2). Intraperitoneal measurements may be an alternative method of monitoring intestinal perfusion after abdominal surgery.

Air↗
PubMed1998

Suppressed neuropeptide Y (NPY) mRNA in rat amygdala following restraint stress.

We have previously demonstrated that NPY produces anxiolytic-like effects through actions in the amygdala, and that anxiogenic-like effects of restraint stress are mediated through this structure. Here, we examined the effects of restraint stress on NPY mRNA levels in amygdala and several other brain regions. A sensitive solution hybridization-RNase protection assay (RPA) was developed, employing a combination of internal and external standards, which allowed absolute quantitation of NPY mRNA in tissue-samples of less than 10 mg. NPY mRNA levels were determined, following a 1-h restraint stress, in homogenates of tissue from the amygdala, neocortex, striatum and hypothalamus, and the time course of these effects was examined. A highly significant decrease in NPY-mRNA levels was seen in the amygdala at 1 h and 2 h following restraint, with levels returning to normal within 10 h. A similar effect was seen in the neocortex, but was less pronounced and slower in onset. Striatal and hypothalamic NPY expression was not significantly affected. Tissue levels of NPY-peptide were modestly decreased in the amygdala at 1 h following restraint and had returned to normal within 4 h. The present findings support the hypothesis that anxiety related behavioral effects of stress may in part be mediated through modulation of NPY function in the amygdala.

Amygdala↗
PubMed1998

High doses of testosterone increase anticonflict behaviour in rat.

Male rats exposed to high levels of testosterone for 8 weeks, or to one high dose of testosterone 24 h before testing, displayed an increase in punished responding in the Vogel conflict test. The findings may be taken as indirect support for the assumption that the conflict paradigm reflects not only anxiety but also impulsivity.

Animals↗
PubMed1998

Sudden infant death syndrome and nitrogen metabolism: further development of a hypothesis.

BACKGROUND: A hypothesis suggesting an inducible inability of the enteric bacteria to metabolize urea in infants, resulting in metabolic alkalosis and subsequent respiratory insufficiency, has been proposed as the cause of sudden infant death syndrome (SIDS). METHODS: Microbiological cultivation and determination of faecal urease activity and faecal urea content were carried out in 30 cases of unexpected infant deaths out of which 22 were considered to be due to SIDS and eight from other causes. The concentration of nitric oxide (NO) in sealed test tubes was determined after incubation of faeces in normal saline. RESULTS: The SIDS subjects differed significantly from the control cases in two respects: they had low or no sigmoid faecal urease activity and an unmetabolized sigmoid faecal urea content, whereas the control subjects had normal faecal urease activity and none, or very little, remaining faecal urea. The NO concentration in faeces was correlated with the faecal content of urea in the SIDS cases. CONCLUSION: The present findings lend support to the hypothesis of an insufficient metabolism of enteric urea in infants with SIDS.

Case-Control Studies↗
PubMed1998

The spread and uptake pattern of intracerebrally administered oligonucleotides in nerve and glial cell populations of the rat brain.

The fate of 15-mer phosphorothioate-modified antisense oligonucleotides to c-fos was followed after their microinjection into rat brain. Using radiolabeled oligonucleotides, it was demonstrated that the bulk of the material stays in the injected region but that a minor part is transported with the projection pathways to regions far away from the site of injection. Using tetramethylrhodamine-isothiocyanate (TRITC) labeling as well as fluorescein isothiocyanate (FITC) labeling, it was found that the oligonucleotides were taken up by a great number of cells within 30 minutes after the injection. A diffuse cytoplasmic staining and also nuclear staining were observed in these cells, which could be identified exclusively as neurons by double labeling for the neuron-specific protein NeuN. At later times (6, 24, and 48 hours), the appearance of the oligonucleotides changed gradually to a punctate cytoplasmic staining, which by electron microscopic analysis was shown to be caused by the presence of the oligonucleotides in intracellular vesicles. The pattern of intracellular fluorescence was changed when the oligonucleotides were injected together with the cationic lipid 1,2-bis(oleoyloxy)-3-(trimethylammonio)propane (DOTAP). A small number of astrocytes and microglial cells were found to be labeled by the oligonucleotides, but only at later times after the injection and exclusively in a punctate cytoplasmic manner. Thus, the uptake of oligonucleotides in the nerve and glial cell populations of the brain might involve different mechanisms, the one in the neurons appearing to be very rapid and potent.

Animals↗
PubMed1998

Systemic oxygen uptake during experimental closed-chest cardiopulmonary resuscitation using air or pure oxygen ventilation.

BACKGROUND: Although clinical cardiopulmonary resuscitation always includes ventilation with pure oxygen, this kind of ventilation has been reported to be associated with worse neurological outcome than ventilation with air in experimental cardiopulmonary resuscitation (CPR). The aim of the present investigation was to compare the systemic oxygen uptake during experimental closed-chest CPR including ventilation with pure oxygen or ambient air and, furthermore, to elucidate possible mechanisms of action in the regulation of pulmonary gas exchange. METHODS: In 24 anesthetized piglets, 2 min of induced ventricular fibrillation and no ventilation was followed by 10 min of closed-chest CPR including i.v. administration of 0.5 mg adrenaline (at 8 min), and in one of the experimental groups alkaline buffer (at 5 min). The piglets were randomly divided into 3 groups: air ventilation during the entire CPR period with saline administration (n=8), air ventilation during the entire CPR period plus tris buffer mixture (n=8), and air ventilation for 3 min followed by 100% oxygen with saline administration (n= 8). RESULTS: In the group ventilated with air and treated with tris buffer mixture, cardiac output was significantly greater than in the group ventilated with pure oxygen. The arterial-mixed venous oxygen content difference was approximately 25% greater with pure oxygen than with air ventilation; however, there was no difference in systemic oxygen uptake. Systemic oxygen uptake increased after administration of tris buffer mixture in the group ventilated with air. CONCLUSIONS: Pulmonary hypoxic vasoconstriction appeared to be abolished during CPR including pure oxygen ventilation. Blood flow, not ventilation or pulmonary gas exchange, is the limiting factor during experimental closed-chest CPR.

Adrenergic Agonists↗
PubMed1998

Guidelines for the treatment of acidaemia with THAM.

THAM (trometamol; tris-hydroxymethyl aminomethane) is a biologically inert amino alcohol of low toxicity, which buffers carbon dioxide and acids in vitro and in vivo. At 37 degrees C, the pK (the pH at which the weak conjugate acid or base in the solution is 50% ionised) of THAM is 7.8, making it a more effective buffer than bicarbonate in the physiological range of blood pH. THAM is a proton acceptor with a stoichiometric equivalence of titrating 1 proton per molecule. In vivo, THAM supplements the buffering capacity of the blood bicarbonate system, accepting a proton, generating bicarbonate and decreasing the partial pressure of carbon dioxide in arterial blood (paCO2). It rapidly distributes through the extracellular space and slowly penetrates the intracellular space, except for erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike bicarbonate, which requires an open system for carbon dioxide elimination in order to exert its buffering effect, THAM is effective in a closed or semiclosed system, and maintains its buffering power in the presence of hypothermia. THAM rapidly restores pH and acid-base regulation in acidaemia caused by carbon dioxide retention or metabolic acid accumulation, which have the potential to impair organ function. Tissue irritation and venous thrombosis at the site of administration occurs with THAM base (pH 10.4) administered through a peripheral or umbilical vein: THAM acetate 0.3 mol/L (pH 8.6) is well tolerated, does not cause tissue or venous irritation and is the only formulation available in the US. In large doses, THAM may induce respiratory depression and hypoglycaemia, which will require ventilatory assistance and glucose administration. The initial loading dose of THAM acetate 0.3 mol/L in the treatment of acidaemia may be estimated as follows: THAM (ml of 0.3 mol/L solution) = lean body-weight (kg) x base deficit (mmol/L). The maximum daily dose is 15 mmol/kg for an adult (3.5L of a 0.3 mol/L solution in a 70kg patient). When disturbances result in severe hypercapnic or metabolic acidaemia, which overwhelms the capacity of normal pH homeostatic mechanisms (pH < or = 7.20), the use of THAM within a 'therapeutic window' is an effective therapy. It may restore the pH of the internal milieu, thus permitting the homeostatic mechanisms of acid-base regulation to assume their normal function. In the treatment of respiratory failure, THAM has been used in conjunction with hypothermia and controlled hypercapnia. Other indications are diabetic or renal acidosis, salicylate or barbiturate intoxication, and increased intracranial pressure associated with cerebral trauma. THAM is also used in cardioplegic solutions, during liver transplantation and for chemolysis of renal calculi. THAM administration must follow established guidelines, along with concurrent monitoring of acid-base status (blood gas analysis), ventilation, and plasma electrolytes and glucose.

Acidosis↗
PubMed1997

Treatment with an antioxidant inhibits vascular changes caused by circulating lymphocytes during acute lung rejection in dogs.

BACKGROUND: Experiments were designed to evaluate the effect of treatment with an inhibitor of lipid peroxidation, H 290/51, on the interaction of lymphocytes and pulmonary arteries during acute lung rejection. It was hypothesized that inhibition of lipid peroxidation would reduce contractions of the pulmonary arteries to autogenous rejection-activated lymphocytes. METHODS: Single-lung transplantation was performed in three groups of dogs: group 1 was maintained on immunosuppression for 8 days postoperatively; in group 2, immunosuppression was discontinued on postoperative day 5, so that rejection occurred on postoperative day 8; in group 3, immunosuppression was discontinued after 5 days, and the lipid peroxidation inhibitor H 290/51 was given orally for 3 days. The pulmonary arteries were removed, cut into rings, and suspended in organ chambers for measurement of isometric force. RESULTS: Macrophage-depleted mononuclear cells (MNCs; lymphocytes) isolated from blood caused cell number-dependent contractions in rings of the pulmonary arteries from all dogs. In the rejecting dogs treated with H 290/51 (group 3), contractions to MNCs were significantly greater in rings without endothelium compared to rings with endothelium. Contractions to MNCs with or without endothelium were reduced by adding deteroxamine to the medium but not by adding superoxide dismutase and catalase. CONCLUSIONS: The results of this study show that treatment with a lipid peroxidation inhibitor, H 290/51, does not prevent acute rejection of transplanted lungs. The treatment with the peroxidation inhibitor modifies contractions of the pulmonary arteries in response to rejection-activated lymphocytes, indicating that reactive oxidative metabolites may be involved in the vasoactive response resulting from this interaction.

Animals↗
PubMed1997

Decreased experimental anxiety and voluntary ethanol consumption in rats following central but not basolateral amygdala lesions.

A long-debated 'tension reduction' hypothesis postulates anti-anxiety effects to be important for ethanol reward, and states that elevated anxiety levels might predispose for ethanol consumption and addiction. Human data are contradictory, possibly due to heterogeneity of patient samples. In rats, baseline levels of experimental anxiety have been reported to correlate with voluntary ethanol consumption. Here, we addressed the possibility that mechanisms underlying experimental anxiety might be causally related to regulation of voluntary ethanol intake. Rats were bilaterally lesioned in central amygdala using microinjections of ibotenic acid. This resulted in a robust release of punished drinking in a modified Vogel conflict test, an effect typically seen with anxiety reducing drugs. This effect was specific, as unpunished drinking was unaffected by the lesion. On the elevated plus-maze, central amygdala lesions did not affect behaviour under baseline conditions, but attenuated the anxiogenic effect of restraint stress. Measures of locomotor activity were not affected. Voluntary ethanol consumption was examined in a two-bottle, free choice paradigm. Ethanol intake was markedly decreased in the lesion group. Total fluid intake was not affected. Basolateral amygdala lesions, which did not affect conflict behaviour, also left ethanol intake unaffected. These results are consistent with previous reports of an important role for central amygdala in anxiety related behaviours, and suggest that cell bodies located in central amygdala might be important in this context. Further, our results support a relation between experimental anxiety and voluntary ethanol consumption.

Alcohol Drinking↗
PubMed1997

Regional distribution of 11C-labeled lidocaine, bupivacaine, and ropivacaine in the heart, lungs, and skeletal muscle of pigs studied with positron emission tomography.

The regional myocardial uptake and kinetics of 11C-lidocaine, 11C-bupivacaine, and 11C-ropivacaine were examined in the pig, utilizing positron emission tomography to determine whether disproportionate distribution exists among these agents. The three drugs were rapidly distributed to the myocardium and lung with mean peak radioactivities occurring between 0.35 and 0.48 min post-injection in myocardium and 0.35 and 0.65 min in lung. Radioactivities peaked later in skeletal muscle than in the myocardium and lung, occurring between 1.1 and 2.7 min post-end injection. Blood radioactivities for bupivacaine and ropivacaine were significantly higher than those of lidocaine, whereas myocardial, lung, and muscle uptakes for the three agents were not significantly different. Myocardium-blood partition coefficients were similar for bupivacaine and ropivacaine (0.55 and 0.49 respectively), while it was three times higher for lidocaine (1.4). A similar relationship existed for skeletal muscle- and lung-blood partition coefficients. Bupivacaine and ropivacaine t1/2z in skeletal muscle were significantly longer than those of lidocaine. The results of this study indicate that the increased cardiotoxicity associated with bupivacaine does not appear to be related to disproportionate distribution in the myocardium when compared to lidocaine and ropivacaine.

Amides↗
PubMed1997

Influence of alkaline buffers on cytoplasmic pH in myocardial cells exposed to hypoxia.

The fluorescent intracellular probe 2',7'-bis-(carboxyethyl)-5,6-carboxyfluorescein acetoxymethyl ester was used in this experimental study to investigate the effects of different alkaline buffers on cytoplasmic pH in suspended myocardial cells under normal as well as hypoxic conditions. A dose-dependent intracellular acidification was achieved after addition of sodium bicarbonate or Tris buffer mixture (Tribonat) to the myocardial cells under normal conditions. After this immediate decrease in cytoplasmic pH, a tendency for the pH to rise again was recorded during the observation period, but this elevation of pH occurred to variable degrees with the different agents and dosages. Addition of larger volumes of Tribonat caused the cytoplasmic pH to return to the initial value during the observation time. Addition of Ringer's acetate produced a significant and persistent cytoplasmic acidification. Larger volumes of Carbicarb as well as pure trometamol (Tris) caused a lasting intracellular alkalinization. Hypoxia per se caused a marked intracellular acidosis in the cardiomyocytes. During hypoxia, addition of sodium bicarbonate caused a further decrease of cytoplasmic pH, turning into an increase during the observation period. Also, Tribonat caused an immediate further acidification, but 15 min after the addition the intracellular pH-value had reached the normal level of normoxic cells. Addition of Ringer's acetate caused a further significant and lasting decrease of intracellular pH. The effect of Carbicarb was a persistent alkalinization of the cell interior. Trometamol produced the most pronounced rise of cytoplasmic pH. In conclusion, this in vitro study shows that Tris buffer mixture (Tribonat) possesses important qualities for correction of metabolic acidosis due to hypoxia and may perhaps be preferred over other alkaline buffers in some situations.

Animals↗
PubMed1997

Response of myocardial cellular energy metabolism to variation of buffer composition during open-chest experimental cardiopulmonary resuscitation in the pig.

The aim of the present study was to investigate possible relationships in piglets between myocardial energy-related metabolites and intracellular electrolytes during open-chest cardiopulmonary resuscitation (OCCPR) supplemented by the administration of alkaline buffers with varying sodium content. Our hypothesis was that an increasing myocardial intracellular sodium content would decrease the intracellular energy stores. In addition to haemodynamics, acid-base and blood gas variables were analysed, and myocardial biopsies were collected before and during OCCPR as well as after the return of spontaneous circulation. After a period of 4 min of untreated ventricular fibrillation (VF). 25 piglets were randomly allocated to one of four groups: OCCPR with normal saline (n = 5); OCCPR with sodium bicarbonate (SB) (n = 7); OCCPR with Tris buffer mixture (TBM) (n = 7); and a totally untreated control group (n = 6). The results showed that 4 min of untreated VF almost eradicated creatine phosphate (CrP) and that the ATP/ADP ratio decreased to 1.5-2.0. During OCCPR with normal saline, the myocardial content of CrP increased, whereas lactate, ATP and ADP levelled off and AMP decreased, causing an increased ATP/ADP ratio. The adenosine and inosine contents increased, whereas inosine monophosphate was unchanged at a low level, the adenosine and inosine contents being inversely correlated with the total content of adenine nucleotides. In both buffered groups, the increase in most energy-related metabolites (CrP, ATP, ADP, AMP and the ATP/ADP quotient) was less and in lactate more pronounced than in the group not being buffered, with no difference between the groups receiving SB or TBM. Although the intracellular potassium content was unaltered, the sodium, chloride and calcium concentration increased, more so in the group receiving SB. The intracellular content of sodium was correlated with that of calcium. Thus, buffering increased the myocardial AMP degradation during OCCPR by increasing the flux via the 5'-nucleotidase reaction, and SB increased the intracellular contents of sodium and calcium to a greater extent than did TBM.

Adenosine Diphosphate↗