| 1. |
- Bjorkman, S, et al.
(författare)
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The effect of thiopental on cerebral blood flow, and its relation to plasma concentration, during simulated induction of anaesthesia in a porcine model
- 1994
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 38:5, s. 473-478
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Tidskriftsartikel (refereegranskat)abstract
- The reversible effect of an induction dose of thiopental on the cerebral blood flow (CBF) was characterized by repeated 133Xe washout measurements during stable physiological conditions in anaesthetized pigs. A thiopental effect corresponding to induction of light and transient anaesthesia was confirmed by electroencephalography (EEG). The concentration (arterial plasma) -effect (-% CBF) relationship of thiopental was estimated using a sigmoidal Emax model. The injection caused a rapid 36 +/- 4.5% (mean +/- s.d.) drop in CBF, with return to baseline by 80 min. According to the pharmacodynamic model, the maximal effect of thiopental (Emax) in this experimental set-up was a 58% lowering of the CBF and the concentration at half-maximal effect (EC50) was 25 micrograms.ml-1. This study provides a complete characterization of the effect of thiopental on the CBF, including the time-course and concentration-effect relationship. A comparison to limited data in the literature suggests that the findings in the pigs constitute a fair approximation of the action of thiopental during the clinical induction of anaesthesia.
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| 2. |
- Messeter, L, et al.
(författare)
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Immunochemical characterization of a monoclonal anti-Leb blood grouping reagent
- 1984
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Ingår i: Vox Sanguinis. - 1423-0410. ; 46:2, s. 66-74
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Tidskriftsartikel (refereegranskat)abstract
- A haemagglutinating monoclonal anti-LebL antibody has been obtained from a mouse-mouse hybridoma after immunization with the Leb-active oligosaccharide lacto-N-difucohexaose I, coupled to edestin. Of 13 other antibodies obtained, one was able to agglutinate enzyme-treated erythrocytes of all ABO groups and three more were considered to be anti-LebH haemagglutinins. The remaining nine antibodies did not agglutinate red cells. The specificity of the stronger of the anti-LebL haemagglutinins was examined by studying its binding to a number of glycoconjugates and oligosaccharides.
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| 3. |
- Nilsson, F, et al.
(författare)
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A porcine model for evaluation of cerebral haemodynamics and metabolism during increased intracranial pressure
- 1995
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 39:6, s. 827-834
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Tidskriftsartikel (refereegranskat)abstract
- In patients with severe head injuries raised intracranial pressure (ICP) constitutes the most important cause of mortality. Several new therapies for increased ICP have recently been suggested and it is of importance to study the physiological effects of these treatments in animal experiments during steady state conditions. A porcine model for evaluation of cerebral haemodynamics and metabolism during increased ICP is presented. Intracranial hypertension was induced by inflation of two tonometric gastric balloons placed extradurally covering a major part of the parietooccipital region bilaterally. The distribution of the blood flow supplied by the carotid artery used for the cerebral blood flow (CBF) measurements was studied by intraarterial (i.a.) injection of 99mTc-HMPAO. The measurements showed that following ligation of the external carotid and the occipital artery no accumulation of tracer substance occurred in extracranial tissues during normal or increased ICP. Cerebral physiological variables (CBF, Cavo2, and ICP) were measured 5, 20 and 60 min after induction of intracranial hypertension. The results confirm that the experimental situation gives a reproducible increase in ICP (25-28 mm Hg) and that the physiological variables remain stable during the period of intracranial hypertension. We conclude that the model simulates the effects of an acute intracranial focal mass and is well suited for the evaluation of different pharmacological therapies of increased ICP.
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| 4. |
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| 5. |
- Åkeson, Jonas, et al.
(författare)
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A porcine model for sequential assessments of cerebral haemodynamics and metabolism
- 1992
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 36:5, s. 419-426
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Tidskriftsartikel (refereegranskat)abstract
- We present a physiologically stable porcine model designed for sequential assessments of pharmacological effects on mean hemispheric cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) at sustained normocapnia. The dynamic influence of continuously administered fentanyl (0.040 mg.kg-1.h-1 i.v.), nitrous oxide (70%) and pancuronium (0.30 mg.kg-1.h-1 i.v.) on these variables was studied in eight normoventilated pigs. CBF was reliably assessable at 10-min intervals by clearance of intra-arterially injected 133Xe, monitored by an extracranial scintillation detector. CMRO2 was calculated from CBF and the simultaneously measured cerebral arteriovenous difference in blood oxygen content. The intracerebral distribution of a contrast medium injected into the external and internal carotid arteries was studied by angiography, and the cerebral venous outflow was investigated by measurements of the distribution of an intra-arterially administered non-diffusible tracer, [99mTc]pertechnetate, to the internal and external jugular veins. After a 3-h equilibration period, CBF and CMRO2 were determined on six occasions over a study period lasting 1 h 40 min. The mean ranges of these variables were 56-60 and 1.9-2.0 ml.100 g-1.min-1, respectively. We conclude that the model enables repeated assessments of CBF and CMRO2 under stable physiological background conditions and thus valid cerebral pharmacodynamic investigations of drugs given for anaesthesia.
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| 6. |
- Åkeson, Jonas, et al.
(författare)
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Cerebral haemodynamic and electrocortical CO2 reactivity in pigs anaesthetized with fentanyl, nitrous oxide and pancuronium
- 1993
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 37:1, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral haemodynamic, metabolic and electrocortical reactivity to alterations in arterial CO2 tension (PaCO2) was assessed in seven mechanically ventilated juvenile pigs to test an experimental model designed for cerebral pharmacodynamic and pharmacokinetic studies. The animals were anaesthetized with fentanyl, nitrous oxide and pancuronium and sequentially normo- and hyperventilated over a 100-min period. Five measurements were made at 25-min intervals. The cerebral blood flow (CBF) was measured with the intra-arterial 133Xe technique and the cerebral metabolic rate for oxygen (CMRO2) determined from CBF and the cerebral arteriovenous oxygen content difference. A linear correlation (r = 0.845) was found between CBF and PaCO2. The cerebrovascular reactivity to hypocapnia (delta CBF/delta PaCO2) was maintained throughout the experimental period and amounted to (95% confidence interval) 9.1 (7.1-11.1) ml x 100 g-1 x min-1 x kPa-1 within the PaCO2 range 3.3-6.3 kPa. The CMRO2 was not influenced by hyperventilation. The baseline electroencephalographic (EEG) pattern was stable at normocapnia (mean PaCO2 5.6 kPa), whereas spectral values for delta and total average voltage increased significantly (P < 0.05) at extensive hypocapnia (3.5 kPa). Maintenance of cerebral CO2 reactivity and spectral EEG voltage at a stable plasma level of fentanyl is complementary to the cerebral haemodynamic and metabolic stability previously found at sustained normocapnia in this model.
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| 7. |
- Åkeson, Jonas, et al.
(författare)
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Cerebral haemodynamic and metabolic effects of hypnotics and analgesics
- 1992
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Ingår i: Annales Francaise D'Anesthesie et de Reanimation. - 0750-7658. ; 11:6, s. 682-684
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in French La sédation des patients neurochirurgicaux fait appel le plus souvent à une association hypnotique-analgésique. Leurs effets sur l'hémodynamique et le métabolisme cérébraux sont l'un des critères qui président au choix des produits. Les analgésiques utilisés seuls, ont peu d'effets sur le flux sanguin cérébral et la CMRO2. Certaines données de la littérature attribuent aux analgésiques une vasodilatation à la fois cérébrale et systémique, chez les patients atteints de lésions cérébrales expansives. Cette notion est controversée. Concernant la kétamine, plusieurs travaux récents proposent son utilisation à doses infra-anesthésiques en association avec le midazolam, sans élévation de la CMRO2. Le propofol et les benzodiazépines diminuent le flux sanguin cérébral et la CMRO2 de façon dose-dépendante. Les baisses excessives du flux sanguin cérébral rapportées dans la littérature seraient à rattacher à la potentialisation d'autres anesthésiques comme les halogénés ou le protoxyde d'azote. Les effets dépresseurs des barbituriques sur le flux sanguin cérébral et la CMRO2 sont bien connus. Les variations quelquefois observées dans la réponse aux barbituriques seraient en rapport, pour les auteurs, avec le maintien ou non de la réactivité vasomotrice cérébrale.
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| 8. |
- Åkeson, Jonas, et al.
(författare)
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Cerebral pharmacodynamics of anaesthetic and subanaesthetic doses of ketamine in the normoventilated pig
- 1993
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 37:2, s. 211-218
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Tidskriftsartikel (refereegranskat)abstract
- There are still divergent opinions regarding the pharmacodynamic effects of ketamine on the brain. In this study, the cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2) and electroencephalographic (EEG) activity were sequentially assessed over 80 min in 17 normoventilated pigs following rapid i.v. infusions of anaesthetic (10.0 mg.kg-1; n = 7) or subanaesthetic (2.0 mg.kg-1; n = 7) doses of ketamine or of its major metabolite norketamine (10.0 mg.kg-1; n = 3). The animals were continuously anaesthetized with fentanyl, nitrous oxide and pancuronium. CBF was determined by the intra-arterial 133Xe technique. Ketamine (10.0 mg.kg-1) induced an instant, gradually reverting decrease in CBF, amounting to -26% (P < 0.01) at 1 min and -13% (P < 0.05) at 10 min, a delayed increase in CMRO2 by 42% (P < 0.01) at 10 min and a sustained rise in low- and intermediate-frequency EEG voltage by 87% at 1 and 97% at 10 min (P < 0.0001). It is concluded that metabolically formed norketamine does not contribute to these effects. Considering the dissociation of CBF from CMRO2 found 10-20 min after ketamine (10.0 mg.kg-1) administration, it is suggested that ketamine should be used with caution for anaesthesia in patients with suspected cerebral ischaemia in order not to increase the vulnerability of brain tissue to hypoxic injury. Ketamine (2.0 mg.kg-1) had no significant effects on CBF, CMRO2 or EEG. It therefore seems that up to one fifth of the minimal anaesthetic i.v. dose can be used safely for analgesia, provided that normocapnaemia is preserved.
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| 9. |
- Åkeson, Jonas, et al.
(författare)
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Low-dose midazolam antagonizes cerebral metabolic stimulation by ketamine in the pig
- 1993
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 37:6, s. 525-531
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Tidskriftsartikel (refereegranskat)abstract
- In order to test the hypothesis that low-dose midazolam reduces excitatory cerebral symptoms by attenuating ketamine-induced increases in the cerebral metabolic rate for oxygen (CMRO2), we compared the cerebral effects of a combination of an anesthetic dose of ketamine hydrochloride (10.0 mg.kg-1 i.v.) and a subanaesthetic dose of midazolam maleate (0.25 mg.kg-1 i.v., n = 6; or 0.10 mg.kg-1 i.v., n = 6) with results recently obtained with ketamine (10.0 mg.kg-1 i.v.) in normoventilated pigs anaesthetized with fentanyl, nitrous oxide and pancuronium. Cerebral blood flow (CBF) was measured with the intra-arterial 133Xe clearance technique, and CMRo2 was calculated from CBF and the cerebral arteriovenous oxygen content difference (CaVO2). The CMRO2 did not increase significantly. In contrast, the maximal increase in cerebral CaVo2 (by 56-59% at 10 min; P < 0.01) was similar to that induced by ketamine, since CBF was more depressed (by 35-45% at 1 min: P < 0.001) by ketamine-midazolam than by ketamine only. Midazolam was found to increase CVR (P < 0.01) and further depress CBF (P < 0.01), and to antagonize the ketamine-induced increase in CMRO2 (P < 0.05). Ketamine-induced effects on mean arterial pressure (MAP) and spectral electroencephalographic (EEG) voltage were not significantly altered by midazolam. The pharmacokinetics of ketamine, as measured during an 80-min period, were not affected by the concomitant administration of midazolam. We propose that a ketamine-midazolam combination comprising a low-dose fraction (1/100-1/40) of midazolam is superior to ketamine alone for anaesthetic use.
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