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| 2. |
- Ahlström, Katarina, 1966, et al.
(författare)
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Exogenous carbon monoxide does not affect cell membrane energy availability assessed by sarcolemmal calcium fluxes during myocardial ischaemia-reperfusion in the pig
- 2011
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Ingår i: European Journal of Anaesthesiology. - 0265-0215 .- 1365-2346. ; 28:5, s. 356-362
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Tidskriftsartikel (refereegranskat)abstract
- Carbon monoxide is thought to be cytoprotective and may hold therapeutic promise for mitigating ischaemic injury. The purpose of this study was to test low-dose carbon monoxide for protective effects in a porcine model of acute myocardial ischaemia and reperfusion. In acute open-thorax experiments in anaesthetised pigs, pretreatment with low-dose carbon monoxide (5% increase in carboxyhaemoglobin) was conducted for 120 min before localised ischaemia (45 min) and reperfusion (60 min) was performed using a coronary snare. Metabolic and injury markers were collected by microdialysis sampling in the ventricular wall. Recovery of radio-marked calcium delivered locally by microperfusate was measured to assess carbon monoxide treatment effects during ischaemia/reperfusion on the intracellular calcium pool. Coronary occlusion and ischaemia/reperfusion were analysed for 16 animals (eight in each group). Changes in glucose, lactate and pyruvate from the ischaemic area were observed during ischaemia and reperfusion interventions, though there was no difference between carbon monoxide-treated and control groups during ischaemia or reperfusion. Similar results were observed for glycerol and microdialysate Ca-45(2+) recovery. These findings show that a relatively low and clinically relevant dose of carbon monoxide did not seem to provide acute protection as indicated by metabolic, energy-related and injury markers in a porcine myocardial ischaemia/reperfusion experimental model. We conclude that protective effects of carbon monoxide related to ischaemia/reperfusion either require higher doses of carbon monoxide or occur later after reperfusion than the immediate time frame studied here. More study is needed to characterise the mechanism and time frame of carbon monoxide-related cytoprotection.
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| 3. |
- Ahlström, Katarina, 1966, et al.
(författare)
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Metabolic responses in ischemic myocardium after inhalation of carbon monoxide.
- 2009
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Ingår i: Acta Anaesthesiol Scand. - : Wiley. - 1399-6576 .- 0001-5172. ; 53:8, s. 1036-42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To clarify the mechanisms of carbon monoxide (CO) tissue-protective effects, we studied energy metabolism in an animal model of acute coronary occlusion and pre-treatment with CO. METHODS: In anesthetized pigs, a coronary snare and microdialysis probes were placed. CO (carboxyhemoglobin 5%) was inhaled for 200 min in test animals, followed by 40 min of coronary occlusion. Microdialysate was analyzed for lactate and glucose, and myocardial tissue samples were analyzed for adenosine tri-phosphate, adenosine di-phosphate, and adenosine mono-phosphate. RESULTS: Lactate during coronary occlusion was approximately half as high in CO pre-treated animals and glucose levels decreased to a much lesser degree during ischemia. Energy charge was no different between groups. CONCLUSIONS: CO in the low-doses tested in this model results in a more favorable energy metabolic condition in that glycolysis is decreased in spite of maintained energy charge. Further work is warranted to clarify the possible mechanistic role of energy metabolism for CO protection.
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| 5. |
- Block, Linda, et al.
(författare)
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A new concept affecting restoration of inflammation-reactive astrocytes.
- 2013
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 250, s. 536-45
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Tidskriftsartikel (refereegranskat)abstract
- Long-lasting pain may partly be a consequence of ongoing neuroinflammation, in which astrocytes play a significant role. Following noxious stimuli, increased inflammatory receptor activity, influences in Na(+)/K(+)-ATPase activity and actin filament organization occur within the central nervous system. In astrocytes, the Ca(2+) signaling system, Na(+) transporters, cytoskeleton, and release of pro-inflammatory cytokines change during inflammation. The aim of this study was to restore these cell parameters in inflammation-reactive astrocytes. We found that the combination of (1) endomorphin-1, an opioid agonist that stimulates the Gi/o protein of the μ-opioid receptor; (2) naloxone, an opioid antagonist that inhibits the Gs protein of the μ-opioid receptor at ultralow concentrations; and (3) levetiracetam, an anti-epileptic agent that counteracts the release of IL-1β, managed to activate the Gi/o protein and Na(+)/K(+)-ATPase activity, inhibit the Gs protein, and decrease the release of IL-1β. The cell functions of astrocytes in an inflammatory state were virtually restored to their normal non-inflammatory state and it could be of clinical significance and may be useful for the treatment of long-term pain.
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| 6. |
- Block, Linda, et al.
(författare)
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Naloxone in ultralow concentration restores endomorphin-1-evoked Ca(2+) signaling in lipopolysaccharide pretreated astrocytes.
- 2012
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 205, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Long-term pain is a disabling condition that affects thousands of people. Pain may be sustained for a long time even after the physiological trigger has resolved. Possible mechanisms for this phenomenon include low-grade inflammation in the CNS. Astrocytes respond to inflammatory stimuli and may play an important role as modulators of the inflammatory response in the nervous system. This study aimed first to assess how astrocytes in a primary culture behave when exposed to the endogenous μ-opioid receptor agonist endomorphin-1 (EM-1), in a concentration-dependent manner, concerning intracellular Ca(2+) responses. EM-1 stimulated the μ-opioid receptor from 10(-15) M up to 10(-4) M with increasing intensity, usually reflected as one peak at low concentrations and two peaks at higher concentrations. Naloxone, pertussis toxin (PTX), or the μ-opioid receptor antagonists CTOP did not totally block the EM-1-evoked Ca(2+) responses. However, a combination of ultralow concentration naloxone (10(-12) M) and PTX (100 ng/ml) totally blocked the EM-1-evoked Ca(2+) responses. This suggests that ultralow (picomolar) concentrations of naloxone should block the μ-opioid receptor coupled G(s) protein, and that PTX should block the μ-opioid receptor coupled G(i/o) protein. The second aim was to investigate exposure of astrocytes with the inflammatory agent lipopolysaccharide (LPS). After 4 h of LPS incubation, the EM-1-evoked Ca(2+) transients were attenuated, and after 24 h of LPS incubation, the EM-1-evoked Ca(2+) transients were oscillated. To restore the EM-1-evoked Ca(2+) transients, naloxone was assessed as a proposed anti-inflammatory substance. In ultralow picomolar concentration, naloxone demonstrated the ability to restore the Ca(2+) transients.
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| 7. |
- Block, Linda, et al.
(författare)
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Ultralow concentrations of bupivacaine exert anti-inflammatory effects on inflammation-reactive astrocytes.
- 2013
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Ingår i: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 38:11, s. 3669-3678
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Tidskriftsartikel (refereegranskat)abstract
- Bupivacaine is a widely used, local anesthetic agent that blocks voltage-gated Na(+) channels when used for neuro-axial blockades. Much lower concentrations of bupivacaine than in normal clinical use, <10(-8) m, evoked Ca(2+) transients in astrocytes from rat cerebral cortex, that were inositol trisphosphate receptor-dependent. We investigated whether bupivacaine exerts an influence on the Ca(2+) signaling and interleukin-1β (IL-1β) secretion in inflammation-reactive astrocytes when used at ultralow concentrations, <10(-8) m. Furthermore, we wanted to determine if bupivacaine interacts with the opioid-, 5-hydroxytryptamine- (5-HT) and glutamate-receptor systems. With respect to the μ-opioid- and 5-HT-receptor systems, bupivacaine restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. With respect to the glutamate-receptor system, bupivacaine, in combination with an ultralow concentration of the μ-opioid receptor antagonist naloxone and μ-opioid receptor agonists, restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. Ultralow concentrations of bupivacaine attenuated the inflammation-induced upregulation of IL-1β secretion. The results indicate that bupivacaine interacts with the opioid-, 5-HT- and glutamate-receptor systems by affecting Ca(2+) signaling and IL-1β release in inflammation-reactive astrocytes. These results suggest that bupivacaine may be used at ultralow concentrations as an anti-inflammatory drug, either alone or in combination with opioid agonists and ultralow concentrations of an opioid antagonist.
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| 8. |
- Block, Linda, et al.
(författare)
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Ultralow Dose of Naloxone as an Adjuvant to Intrathecal Morphine Infusion Improves Perceived Quality of Sleep but Fails to alter Persistent Pain: A Randomized, Double-blind, Controlled Study.
- 2015
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Ingår i: The Clinical journal of pain. - 1536-5409. ; 31:11, s. 968-975
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Tidskriftsartikel (refereegranskat)abstract
- This randomized, cross-over, double-blind, controlled study of continuous intrathecal morphine administration in patients with severe, long-term pain addresses whether the supplementation of low doses of naloxone in this setting is associated with beneficial clinical effects. All of the study subjects (n=11) provided informed consent and were recruited from a subset of patients who were already undergoing long-term treatment with continuous intrathecal morphine because of difficult-to-treat pain. The patients were (in a randomized order) also given intrathecal naloxone (40 ng/24 h or 400 ng/24 h). As control, the patients' ordinary dose of morphine without any additions was used. The pain (Numeric Rating Scale, NRS) during activity, perceived quality of sleep, level of activity and quality of life as well as the levels of several pro- and anti-inflammatory cytokines in the blood were assessed. The pre-study pain (NRS during activity) in the study group ranged from 3 to 10. 64% of the subjects reported improved quality of sleep during treatment with naloxone at a dose of 40 ng/24 hours compared with 9% with sham treatment (P=0.024). Although not statistically significant, pain was reduced by 2 NRS steps or more during supplemental treatment with naloxone in 36% of subjects when using the 40 ng/24 hours dose and in 18% of the subjects when using a naloxone 400 ng/24 hours dose. The corresponding percentage among patients receiving unaltered treatment was 27%. To conclude, the addition of an ultralow dose of intrathecal naloxone (40 ng/24 h) to intrathecal morphine infusion in patients with severe, persistent pain improves perceived quality of sleep. We were not able to show any statistically significant effects of naloxone on pain relief, level of activity or quality of life.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
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| 9. |
- Bohm, Katarina, et al.
(författare)
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Dispatcher-assisted telephone-guided cardiopulmonary resuscitation: an underused lifesaving system.
- 2007
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Ingår i: Eur J Emerg Med. - 0969-9546. ; 14:5, s. 256-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Our purpose with this investigation was to (i) estimate how often telephone-guided cardiopulmonary resuscitation was offered from emergency medical service dispatchers in Stockholm, (ii) study the willingness to perform cardiopulmonary resuscitation, and (iii) assess factors that could mislead the dispatcher in identifying the patient as a cardiac arrest victim. METHODS: In this prospective study, 313 consecutive emergency calls of out-of-hospital cardiac arrest were obtained from the Swedish Cardiac Arrest Register. Seventy-six cases of out-of-hospital cardiac arrest fulfilled the inclusion criteria. All alarm calls were tape-recorded and analyzed according to a standardized protocol. RESULTS: Dispatchers offered bystanders telephone instructions for cardiopulmonary resuscitation in 47% (n=36) of the cases and, among these, cardiopulmonary resuscitation instructions were given in 69% (n=25). Only 6% (n=2) of bystanders were not willing to perform cardiopulmonary resuscitation. Signs of breathing (suspected agonal breathing) were described in 45% of the cases. Cardiopulmonary resuscitation was offered to 23% (n=10) of patients with signs of breathing versus 92% (n=23) of those who were not breathing (P<0.001). CONCLUSIONS: Despite the fact that the vast majority of bystanders are willing to take part in telephone-guided cardiopulmonary resuscitation, emergency medical service dispatchers offer telephone-guided cardiopulmonary resuscitation in about only half of cases. Signs of breathing (agonal breathing) are often mistaken for normal breathing and are a cause of delay in the diagnosis of cardiac arrest.
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| 10. |
- Broomé, Michael, et al.
(författare)
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Pressure-independent cardiac effects of angiotensin II in pigs.
- 2004
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Ingår i: Acta Anaesthesiol Scand. - 0001-6772 .- 1365-201X. ; 182:2, s. 111-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Angiotensin II (Ang II) is a potent vasoconstrictor with an important role in the development of cardiovascular disease. Earlier results have shown a positive acute inotropic effect of Ang II in anaesthetized pigs together with significant vasoconstriction. This investigation was designed to study cardiac effects of Ang II, when blood pressure was maintained constant by experimental means. METHODS: Ang II (200 microg h(-1)) was infused in anaesthetized pigs (n = 10) at two different arterial blood pressures, the first determined by the effects of Ang II alone, and the second maintained at baseline blood pressure with nitroprusside. Cardiac systolic and diastolic function was evaluated by analysis of left ventricular pressure-volume relationships. RESULTS: Heart rate, end-systolic elastance (Ees) and pre-load adjusted maximal power (PWRmax EDV(-2)) increased at both blood pressure levels, although less when blood pressure was kept constant with nitroprusside. The time constant for isovolumetric relaxation (tau(1/2)) was prolonged with Ang II alone and shortened with Ang II infused together with nitroprusside. CONCLUSION: Ang II infusion in the pig has inotropic and chronotropic properties independent of arterial blood pressure levels, although the effects seem to be blunted by pharmacological actions of the nitric oxide donor nitroprusside.
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