| 1. |
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| 2. |
- Ahlström, Katarina, 1966, et al.
(author)
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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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In: European Journal of Anaesthesiology. - 0265-0215 .- 1365-2346. ; 28:5, s. 356-362
-
Journal article (peer-reviewed)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.
(author)
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Metabolic responses in ischemic myocardium after inhalation of carbon monoxide.
- 2009
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In: Acta Anaesthesiol Scand. - : Wiley. - 1399-6576 .- 0001-5172. ; 53:8, s. 1036-42
-
Journal article (peer-reviewed)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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| 4. |
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| 5. |
- Block, Linda, et al.
(author)
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A new concept affecting restoration of inflammation-reactive astrocytes.
- 2013
-
In: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 250, s. 536-45
-
Journal article (peer-reviewed)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.
(author)
-
Naloxone in ultralow concentration restores endomorphin-1-evoked Ca(2+) signaling in lipopolysaccharide pretreated astrocytes.
- 2012
-
In: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 205, s. 1-9
-
Journal article (peer-reviewed)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.
(author)
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Ultralow concentrations of bupivacaine exert anti-inflammatory effects on inflammation-reactive astrocytes.
- 2013
-
In: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 38:11, s. 3669-3678
-
Journal article (peer-reviewed)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.
(author)
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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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In: The Clinical journal of pain. - 1536-5409. ; 31:11, s. 968-975
-
Journal article (peer-reviewed)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.
(author)
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Dispatcher-assisted telephone-guided cardiopulmonary resuscitation: an underused lifesaving system.
- 2007
-
In: Eur J Emerg Med. - 0969-9546. ; 14:5, s. 256-9
-
Journal article (peer-reviewed)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.
(author)
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Pressure-independent cardiac effects of angiotensin II in pigs.
- 2004
-
In: Acta Anaesthesiol Scand. - 0001-6772 .- 1365-201X. ; 182:2, s. 111-9
-
Journal article (peer-reviewed)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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| 11. |
- Claesson, Jonas, et al.
(author)
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Evaluation of intestinal preconditioning in a porcine model using classic ischemic preconditioning or lung recruitment maneuvers.
- 2008
-
In: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322 .- 1540-0514. ; 21:1, s. 98-103
-
Journal article (peer-reviewed)abstract
- To test the hypotheses that repeated brief intestinal ischemic insults would elicit an intestinal preconditioning response to a subsequent intestinal I/R injury and that a similar response would be elicited by repeated lung recruitment maneuvers (RMs). Randomized experimental controlled animal study. University hospital animal laboratory. Eighteen anesthetized pigs. Animals were randomized to one of three groups, with six animals in each group. Control group 75-min superior mesenteric artery (SMA) occlusion followed by 60-min reperfusion. Ischemic preconditioning group, three 5-min-long SMA occlusions preceding 75-min SMA occlusion and 60-min reperfusion. Recruitment maneuver (RM) group, three 2-min-long RMs preceding 75-min SMA occlusion and 60-min reperfusion. We measured systemic and mesenteric hemodynamic parameters, jejunal mucosal perfusion, net mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygenation. Every 15 min, jejunal microdialysate samples were collected and analyzed for glucose, lactate, and glycerol. Jejunal tissue samples were collected postmortem. After occlusion of SMA, regional parameters in all groups indicated abolished perfusion and gradually increasing intraluminal microdialysate lactate and glycerol levels. At reperfusion, regional parameters indicated mesenteric hyperperfusion, whereas microdialysis markers of mucosal anaerobic metabolism and cell injury decreased, although not reaching baseline. Histological examination revealed severe mucosal injury in all groups. There were no significant differences between groups in the observed parameters. No protective preconditioning response could be observed when performing repeated brief intestinal ischemic insults or repeated lung RMs before an intestinal I/R injury.
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| 12. |
- Forshammar, Johan, et al.
(author)
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Anti-inflammatory substances can influence some glial cell types but not others.
- 2013
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In: Brain research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 1539, s. 34-40
-
Journal article (peer-reviewed)abstract
- In rat microglial enriched cultures, expressing Toll-like receptor 4, we studied cytokine release after exposure with 1ng/ml LPS for 0.5-24h. Dexamethasone and corticosterone exposure served as controls. We focused on whether naloxone, ouabain, and bupivacaine, all agents with reported anti-inflammatory effects on astrocytes, could affect the release of TNF-α and IL-1β in microglia. Our results show that neither ultralow (10(-12)M) nor high (10(-6)M) concentrations of these agents had demonstrable effects on cytokine release in microglia. The results indicate that anti-inflammatory substances exert specific influences on different glial cell types. Astrocytes seem to be functional targets for anti-inflammatory substances while microglia respond directly to inflammatory stimuli and are thus more sensitive to anti-inflammatory substances like corticoids. The physiological relevance might be that astrocyte dysfunction influences neuronal signalling both due to direct disturbance of astrocyte functions and in the communication within the astrocyte networks. When the signalling between astrocytes is working, then microglia produce less pro-inflammatory cytokines.
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| 13. |
- Forshammar, Johan, et al.
(author)
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Naloxone and Ouabain in Ultralow Concentrations Restore Na+/K+-ATPase and Cytoskeleton in Lipopolysaccharide-treated Astrocytes.
- 2011
-
In: The Journal of biological chemistry. - 1083-351X. ; 286:36, s. 31586-97
-
Journal article (peer-reviewed)abstract
- Astrocytes respond to inflammatory stimuli and may be important modulators of the inflammatory response in the nervous system. This study aimed first to assess how astrocytes in primary culture behave in response to inflammatory stimuli concerning intracellular Ca(2+) responses, expression of Toll-like receptor 4 (TLR4), Na(+)/K(+)-ATPase, actin filament organization, and expression of cytokines. In a cell culture model with lipopolysaccharide (LPS), astrocyte response was assessed first in the acute phase and then after incubation with LPS for 1-48 h. The concentration curve for LPS-stimulated Ca(2+) responses was bell-shaped, and the astrocytes expressed TLR4, which detects LPS and evokes intracellular Ca(2+) transients. After a long incubation with LPS, TLR4 was up-regulated, LPS-evoked Ca(2+) transients were expressed as oscillations, Na(+)/K(+)-ATPase was down-regulated, and the actin filaments were disorganized. Interleukin-1β (IL-1β) release was increased after 24 h in LPS. A second aim was to try to restore the LPS-induced changes in astrocytes with substances that may have dose-dependent anti-inflammatory properties. Naloxone and ouabain were tested separately in ultralow or high concentrations. Both substances evoked intracellular Ca(2+) transients for all of the concentrations from 10(-15) up to 10(-4) m. Neither substance blocked the TLR4-evoked Ca(2+) responses. Naloxone and ouabain prevented the LPS-induced down-regulation of Na(+)/K(+)-ATPase and restored the actin filaments. Ouabain, in addition, reduced the IL-1β release from reactive astrocytes. Notably, ultralow concentrations (10(-12) m) of naloxone and ouabain showed these qualities. Ouabain seems to be more potent in these effects of the two tested substances.
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| 14. |
- Fröjse, R, et al.
(author)
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Assessment of graded intestinal hypoperfusion and reperfusion using continuous saline tonometry in a porcine model.
- 2004
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In: Eur J Vasc Endovasc Surg. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 28:1, s. 79-88
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate effects of graded intestinal hypoperfusion and reperfusion on intestinal metabolic parameters as assessed by a modified continuous saline tonometry technique. MATERIALS: Twelve barbiturate-anaesthetized female pigs. METHODS: Measurements were performed prior to and during three predefined levels of superior mesenteric mean arterial blood pressure (P(SMA) 70, 50 and 30 mmHg, respectively, each 80 min long), obtained by an adjustable clamp around the origin of the superior mesenteric artery, and during reperfusion. We continuously measured jejunal mucosal perfusion (laser Doppler flowmetry), jejunal tissue oxygen tension (PO(2TISSUE); microoximetry) and intramucosal PCO(2) (continuous saline tonometry) and calculated net intestinal lactate production, mesenteric oxygenation, PCO(2) gap (jejunal mucosal PCO(2)-arterial PCO(2)) and pHi. RESULTS: At P(SMA) 70 and 50 mmHg mesenteric oxygen uptake and net lactate production remained unaltered, in spite of decreased oxygen delivery. At these P(SMA) levels PCO(2) gap increased, while pHi and PO(2TISSUE) decreased. At P(SMA) 30 mmHg pronounced increases in PCO(2) gap and mesenteric net lactate production as well as marked decreases in PO(2TISSUE) and pHi were demonstrated. Data indicate absence of anaerobic conditions at an intestinal perfusion pressure (IPP)> or =41 mmHg, a pHi> or =7.22 or PCO(2) gap< or =15.8 mmHg. CONCLUSIONS: Continuous saline tonometry detected intestinal ischemia as induced by graded reductions in IPP. A threshold could be defined above which intestinal ischemia does not occur.
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| 15. |
- Fröjse, R, et al.
(author)
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Local metabolic effects of dopexamine on the intestine during mesenteric hypoperfusion.
- 2004
-
In: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322 .- 1540-0514. ; 21:3, s. 241-7
-
Journal article (peer-reviewed)abstract
- This self-controlled experimental study was designed to test the hypothesis that dopexamine, a synthetic catecholamine that activates dopaminergic (DA-1) and beta2-adrenergic receptors, improves oxygenation in the jejunal mucosa during intestinal hypotension. In six normoventilated barbiturate-anesthetized pigs, controlled reductions in superior mesenteric arterial pressure (PSMA) was obtained by an adjustable clamp around the artery. Dopexamine infusions (0.5 and 1.0 microg.kg(-1).min(-1)) were administered at a freely variable PSMA (i.e., with the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. We continuously measured superior mesenteric venous blood flow (QMES; transit-time ultrasonic flowmetry), jejunal mucosal perfusion (laser Doppler flowmetry), and tissue oxygen tension (PO2TISSUE; microoximetry). Jejunal luminal microdialysate of lactate, pyruvate, and glucose were measured every 5 min. Measurements of mucosal PCO2 (air tonometry), together with blood sampling and end-tidal PCO2 measurements, enabled calculations of pHi and PCO2 gap. Dopexamine reduced mesenteric vascular resistance and increased QMES at a PSMA of 50 mmHg and 30 mmHg. At a PSMA of 30 mmHg, dopexamine increased mesenteric oxygen delivery but did not influence mesenteric oxygen uptake or extraction. In this situation, dopexamine had no beneficial effect on jejunal mucosal blood flow. On the contrary, dopexamine increased mesenteric net lactate production and PCO2 gap, whereas PO2TISSUE and pHi decreased. Jejunal luminal microdialysate data demonstrated an increased lactate concentration and a pattern of decreased glucose concentration and increased luminal lactate-pyruvate ratio. These negative metabolic effects of dopexamine should be taken into account in situations of low perfusion pressures.
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| 16. |
- Gordh, Torsten E, et al.
(author)
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Gabapentin in traumatic nerve injury pain : a randomized, double-blind, placebo-controlled, cross-over, multi-center study
- 2008
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In: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 138:2, s. 255-266
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Journal article (peer-reviewed)abstract
- A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400 mg/day. The study comprised a run-in period of two weeks, two treatment periods of five weeks separated by a three weeks' washout period. The primary efficacy variable was the change in the mean pain intensity score from baseline to the last week of treatment. Other variables included pain relief, health related quality of life (SF-36), interference of sleep by pain, Clinician and Patient Global Impression of Change, and adverse effects. Nine centers randomized a total of 120 patients, 22 of whom withdrew. There was no statistically significant difference between the treatments for the primary outcome efficacy variable. However, gabapentin provided significantly better pain relief (p=0.015) compared with placebo. More patients had at least a 30% pain reduction with gabapentin compared with placebo (p=0.040) and pain interfered significantly less with sleep during gabapentin treatment compared with placebo (p=0.0016). Both the Patient (p=0.023) and Clinician (p=0.037) Global Impression of Change indicated a better response with gabapentin compared with placebo. Gabapentin was well tolerated. The most common adverse effects were dizziness and tiredness.
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| 17. |
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| 18. |
- Hallén, Katarina, et al.
(author)
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Transcutaneous electrical nerve stimulation induces vasodilation in healthy controls but not in refractory angina patients.
- 2010
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In: Journal of pain and symptom management. - : Elsevier BV. - 1873-6513 .- 0885-3924. ; 40:1, s. 95-101
-
Journal article (peer-reviewed)abstract
- CONTEXT: Transcutaneous electrical nerve stimulation (TENS) is an effective treatment option to relieve ischemic pain in refractory angina pectoris (RAP). In healthy persons, TENS enhances local blood flow, but the mechanism responsible for the anti-ischemic effect in RAP seems to be different. OBJECTIVE: The aim of the present investigation was to compare the difference in blood flow and vasodilatory response to TENS between angina patients and healthy controls and evaluate how vascular response in these groups is affected by amperage dosage above and below motor threshold levels. METHODS: Our study evaluated upper limb vascular responses to low- and high-dose TENS (below and above motor threshold) in RAP patients compared with healthy controls. TENS was applied on the nondominating forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Forearm vascular resistance (FVR) was determined (mean arterial pressure [MAP]/FBF). Measurements were done during baseline, low-dose TENS, high-dose TENS, and during recovery. RESULTS: A significant dose-dependent increase in FBF in response to TENS stimulation was seen in controls (n=18) but not in RAP (n=23) (P=0.008). There was no significant difference in FVR ratio (FVR(stim)/FVR(ctrl)) between control (n=7) and RAP (n=23) groups at low dose (controls, 5.7+/-21%; RAP, 9.7+/-20%) or recovery (controls, -4.6+19%; RAP, 5.9+25%). High-dose TENS resulted in a significantly reduced FVR ratio (-16.8+/-11%) in controls (n=7) compared with RAP (1.6+/-32%, n=23) (P=0.02). CONCLUSION: High-dose TENS induces forearm vasodilation in healthy subjects but not in patients with RAP. These findings suggest that TENS has different vascular effects in patients with severe coronary artery disease compared with healthy controls.
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| 19. |
- Haney, Michael, et al.
(author)
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Beat-to-beat change in "myocardial performance index" related to load.
- 2007
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In: Acta Anaesthesiol Scand. - : Wiley. - 0001-5172 .- 1399-6576. ; 51:5, s. 545-52
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Journal article (peer-reviewed)abstract
- BACKGROUND: This study was designed to assess the relationship of the "myocardial performance index" (MPI) to the beat-by-beat change in pre-load with static or unchanged contractile status. METHODS: Eight anesthetized juvenile pigs were studied using direct measurement of the left ventricular pressure and volume. Transient inflation of a vena cava balloon catheter produced controlled pre-load alterations. Consecutive beats were analyzed, grouped for first, second, third, etc. during the pre-load alteration, and evaluated for the change in MPI during the same contractile status with a controlled pre-load alteration. Two pharmacologic inotropic interventions were also included to generate several myocardial conditions in each animal. RESULTS: MPI demonstrated a strong linear relationship to the pre-load and after-load. MPI increased progressively during decreasing end-diastolic volume, mostly related to changes in ejection time. MPI was observed at the same level for three different myocardial function conditions (all eight animals), with a different relationship between MPI and pre-load noted for each observation. CONCLUSIONS: MPI is strongly load dependent, and can vary widely in value for the same contractile status if the load is varied. The use of this index in critically ill patients should be limited in this respect. Further work is needed to establish the relationship of MPI to load and contractile status.
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| 20. |
- Haney, Michael F, et al.
(author)
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Myocardial systolic function increases during positive pressure lung inflation.
- 2005
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In: Anesth Analg. - 0003-2999. ; 101:5, s. 1269-74
-
Journal article (peer-reviewed)abstract
- Lung inflation with positive airway pressure may have rapid and dynamic effects on myocardial contractile function. We designed this study to assess the magnitude and time to onset of myocardial function changes during the initiation of single positive pressure lung inflation at clinically relevant inflation pressures. In 8 anesthetized 40-kg pigs, left ventricular pressures and volumes were measured directly (conductance volumetry). A 15 cm H2O airway pressure plateau with lung inflation (PPLI-15) was performed, and 2 single beats from that sequence, one from resting apnea at zero airway pressure and the second from the point when the lungs were first maximally inflated, were selected for analysis. Systolic function variables for zero airway pressure and PPLI-15 were analyzed. Systolic elastance, derived from bilinear time-varying elastance curves, increased approximately 15% during PPLI-15 from zero airway pressure. This agreed with other systolic function variables that identified an increase in left ventricular contractile function for the lung inflation beat. Serial measurements of myocardial function should be conducted with constant airway pressure and lung inflation conditions.
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| 21. |
- Haney, Michael F, et al.
(author)
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The effect of lung inflation on absolute ventricular volume measurement by conductance.
- 2006
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In: Clin Physiol Funct Imaging. - 1475-0961. ; 26:4, s. 220-3
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Journal article (peer-reviewed)abstract
- BACKGROUND: Conductance catheter in vivo ventricular volume measurements during lung ventilation may provide important information on left ventricular (LV) function. Breathing potentially may alter parallel conductance (V(c)), complicating interpretation of the conductance-derived volume signals. The effects of controlled positive pressure lung inflation (PPLI) on measured parallel conductance with dual-field conductance volumetry were investigated. METHODS: Eight anaesthetized pigs were instrumented with an LV dual-field conductance volumetry catheter. V(c) was measured repeatedly, using the hypertonic saline injection method, at three different levels of lung insufflation: continuous positive airway pressure (PPLI) 0, 5, and 10 cm H(2)O. RESULTS: V(c)s measured at PPLI 0, 5 and 10 cm H(2)O were 70.9 +/- 4.8, 70.7 +/- 5.5 and 70.5 +/- 5.9 ml, respectively. The corresponding uncalibrated end-diastolic volumes (EDV(u)) were 115.5 +/- 7.1, 117.0 +/- 7.5 and 117.5 +/- 7.7 ml, respectively. Mean coefficients of variance for V(c) and EDV(u) at all three PPLI levels were 3.8% and 1.25%, respectively. DISCUSSION: Several levels of PPLI demonstrated no systematic change in parallel conductance for LV dual-field conductance volume signal. We concluded that lung inflation at these levels does not generate changes in V(c).
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| 22. |
- Häggmark, Sören, et al.
(author)
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Vectorcardiographic ST deviations related to increased heart rate in the absence of ischemia in an experimental pig model.
- 2006
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In: J Electrocardiol. - : Elsevier BV. - 0022-0736 .- 1532-8430. ; 39:2, s. 169-76
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Journal article (peer-reviewed)abstract
- The electrocardiographic ST segment may change when heart rate (HR) increases. We aimed to analyze vectorcardiographic ST relation and myocardial conditions during controlled HR increases in anesthetized pigs. The relative parameters ST change vector magnitude and ST change vector angle were calculated at paced HRs ranging from 85 to 175 beats per minute. ST change vector magnitude increased from baseline 6.3 +/- 1.3 to 26.0 +/- 3.1 microV (P < .01; range, 4-50 microV) at HR 175 beats per minute with similar changes in ST change vector angle, whereas the absolute parameter ST vector magnitude demonstrated a heterogeneous pattern without any systematic relation to HR changes. Microdialysis results from left ventricular wall, with analysis of glucose, lactate, and pyruvate, showed no sign of ischemia during pacing. Potassium concentrations did not change during pacing. We conclude that significant HR-related ST vector changes can occur in the absence of myocardial ischemia.
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| 23. |
- Konrad, D, et al.
(author)
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Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo.
- 2005
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In: Am J Physiol Heart Circ Physiol. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 289:4
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Journal article (peer-reviewed)abstract
- The endothelin (ET) system is involved in the regulation of myocardial function in health as well as in several diseases, such as congestive heart failure, myocardial infarction, and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of ET-1. We therefore investigated the effects of intracoronary infusions of ET-1 and of the selective ET(B) receptor-selective agonist sarafotoxin 6c with increasing doses in anesthetized pigs. Myocardial effects were measured through analysis of the left ventricular pressure-volume relationship. ET-1 elicited increases in the myocardial contractile status (end-systolic elastance value of 0.94 +/- 0.11 to 1.48 +/- 0.23 and preload recruitable stroke work value of 68.7 +/- 4.7 to 83.4 +/- 7.2) that appear to be mediated through ET(A) receptors, whereas impairment in left ventricular isovolumic relaxation (tau = 41.5 +/- 1.4 to 58.1 +/- 5.0 and t(1/2) = 23.0 +/- 0.7 to 30.9 +/- 2.6, where tau is the time constant for pressure decay and t(1/2) is the half-time for pressure decay) was ET(B) receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c administration caused impairments in left ventricular relaxation (tau from 43.3 +/- 1.8 to 54.4 +/- 3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ET(A) and ET(B) receptor activation, respectively.
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| 24. |
- Lindnér, Per, 1956, et al.
(author)
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Hepatic artery occlusion and energy charge in rat liver tumour.
- 1994
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In: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - 0923-7534. ; 5:10, s. 961-3
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Journal article (peer-reviewed)abstract
- Hepatic artery ligation (HAL) is a model for inducing a vascular attack on liver tumours which causes a reduction in tumour growth. To determine in an experimental rat liver adenocarcinoma the duration and magnitude of changes in adenonucleotide concentration and energy charge (EC) after HAL, analyses of energy-rich nucleotides were performed at 1, 2, 24 and 168 hours after HAL or a SHAM procedure. There was a significant decrease of the ATP content and energy charge in the tumour one hour after HAL. Two hours after HAL this difference had decreased and with longer observation it was not detectable. Twenty-four hours of starvation did not significantly alter the effects of HAL on the tumour. HAL gives rise to a transient energy depletion of the tumour which is not completely compensated for by glycolysis after 1 hour, but is restored after 2 hours.
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| 25. |
- Lundberg, J F, et al.
(author)
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Dopamine or norepinephrine infusion during thoracic epidural anesthesia? Differences in hemodynamic effects and plasma catecholamine levels.
- 2005
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In: Acta Anaesthesiol Scand. - : Wiley. - 0001-5172. ; 49:7, s. 962-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: During thoracic epidural anesthesia, an intravenous dopamine infusion augments the systemic pressure response and modifies plasma catecholamine levels. If such an altered response occurs when norepinephrine is infused is not clear. Therefore, dopamine and norepinephrine induced circulatory and catecholamine responses were studied before and during thoracic epidural anesthesia. METHODS: Nine chloralose-anesthetized dogs were equipped with thoracic epidural catheters. Dopamine (5, 10, and 20 microg kg(-1) min(-1)), and norepinephrine (0.1, 0.25, and 0.5 microg kg(-1) min(-1)) were infused before and during epidural anesthesia, while cardiovascular performance and plasma catecholamine changes were studied. RESULTS: Thoracic epidural anesthesia decreased arterial pressure, and cardiac contractility. The systemic pressure response induced by dopamine was augmented during epidural anesthesia. Norepinephrine did not increase arterial pressure and myocardial contractility as markedly as dopamine, and cardiac output was not altered. Thoracic epidural anesthesia attenuated the plasma norepinephrine level. Plasma dopamine levels were augmented by the dopamine infusion during epidural anesthesia, while plasma norepinephrine levels were attenuated. In contrast, norepinephrine augmented the plasma norepinephrine levels during epidural anesthesia. In general, plasma norepinephrine levels were three to six times higher during a norepinephrine infusion compared to a dopamine infusion. CONCLUSION: The cardiovascular response to a graded dopamine infusion is augmented during thoracic epidural anesthesia, while norepinephrine-induced effects are unaltered. The modified plasma catecholamine levels may contribute to the hemodynamic differences between dopamine and norepinephrine infusions during thoracic epidural anesthesia.
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| 26. |
- Lundborg, Christopher, 1965, et al.
(author)
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Glial cell line-derived neurotrophic factor is increased in cerebrospinal fluid but decreased in blood during long-term pain.
- 2010
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In: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 220:1-2, s. 108-113
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Journal article (peer-reviewed)abstract
- Glial cell line-derived neurotrophic factor (GDNF) is involved in inflammation and pain, roles which remain to be delineated clinically. We aimed to evaluate the role of central nervous and peripheral GDNF in long-term pain patients and in controls by analysing intrathecal and blood concentrations of GDNF. Simultaneous measurements of pro-inflammatory cytokines IL-1beta, TNF-alpha and IL-6, anti-inflammatory cytokine IL-10 and chemokine IL-8 served to define inflammatory responses. Generally, blood levels of GDNF were higher than corresponding intrathecal levels. Pain was associated with levels of GDNF that were increased intrathecally, but decreased in blood. IL-8 was uniformly higher in pain patients.
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| 27. |
- Lundborg, Christopher, 1965, et al.
(author)
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High intrathecal bupivacaine for severe pain in the head and neck.
- 2009
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In: Acta Anaesthesiol Scand. - : Wiley. - 1399-6576. ; 53:7, s. 908-13
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Journal article (peer-reviewed)abstract
- BACKGROUND: Severe pain in the head and neck is associated with a lowered quality of life and conventional pain therapy often does not provide adequate relief. The aims of this study were to investigate the efficacy, pain relief, benefits and adverse effects of intracisternal or high cervical (IHC) administration of bupivacaine in patients with severe pain in the head, neck and face regions. METHODS: Between 1990 and 2005, 40 patients (age 27-84 years) were treated with continuous IHC infusions of bupivacaine for various non-cancer (n=15) or cancer-related (n=25) refractory pain conditions (duration 1 month-18 years) in the head, neck, mouth and shoulder regions. RESULTS: Visual analogue scale scores and opioid requirements decreased markedly after the start of the treatment and remained lowered throughout the study. No tachyphylaxis for bupivacaine was observed. Major side effects were few and most often transient. Most patients showed unchanged or improved mobility. There was no mortality, neurological damage or other severe events attributable to procedures in the study protocol. CONCLUSION: For patients with severe and refractory pain in areas innervated by cranial and upper cervical nerves, cervical high spinal analgesia can provide safe and effective analgesia.
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| 28. |
- Lundborg, Christopher, 1965, et al.
(author)
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Ifenprodil restores GDNF-evoked Ca(2+) signalling and Na(+) /K(+) -ATPase expression in inflammation-pretreated astrocytes.
- 2011
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In: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 119:4, s. 686-696
-
Journal article (peer-reviewed)abstract
- ABSTRACT: Glial cell line-derived neurotrophic factor (GDNF) plays an important role in neuroinflammatory and neuropathic pain conditions. Astrocytes produce and secrete GDNF, which interacts with its receptors to induce Ca(2+) transients. This study aimed first to assess intracellular Ca(2+) responses of astrocytes in primary culture when exposed to the neuroprotective and anti-inflammatory peptide GDNF. Furthermore, incubation with the inflammatory inducers lipopolysaccharide (LPS), NMDA, or interleukin 1-β (IL-1β) attenuated the GDNF-induced Ca(2+) transients. The next aim was to try to restore the suppressed GDNF responses induced by inflammatory changes in the astrocytes with an anti-inflammatory substance. Ifenprodil, an NMDA receptor antagonist at the NR2B subunit, was tested. It was shown to restore the GDNF-evoked Ca(2+) transients and increased the Na(+) /K(+) -ATPase expression. Ifenprodil seems to be a potent anti-inflammatory substance for astrocytes which have been pre-activated by inflammatory stimuli.
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| 29. |
- Nurmi, Jouni, et al.
(author)
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Effect of protocol compliance to cardiac arrest identification by emergency medical dispatchers.
- 2006
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In: Resuscitation. - : Elsevier BV. - 0300-9572. ; 70:3, s. 463-9
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The objective of the study was to assess the effect of protocol compliance to the accuracy of cardiac arrest (CA) identification by the dispatchers. METHODS: The study was conducted prospectively over a 1-year period in 1996. The calls categorized as non-traumatic CAs by the dispatcher and calls where the patient was in non-traumatic CA when ambulance crew arrived were included in the study. The data was collected from emergency call tape recordings and ambulance run sheets. The compliance to the protocol was defined as gathering information to two questions: (1) Is the patient awake or can she/he be awakened? and (2) Is she/he breathing normally? RESULTS: The number of calls included in the study was 776 and the dispatchers identified 83% of the CAs. The protocol was adhered in 52.4% of calls, more often in witnessed than unwitnessed cases (72.3% versus 45.0%, P<0.001). In correctly identified CAs, the protocol compliance was 49.4%. The compliance was higher in cases of unidentified CAs (60.3%, P=0.0326) and in cases of wrongly identified as CAs (false positives, 61.9%, P=0.0276). CONCLUSIONS: A high identification rate of CAs seems to be achievable despite poor protocol compliance by dispatchers.
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| 30. |
- Raposo, C., et al.
(author)
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Neuropharmacological effects of Phoneutria nigriventer venom on astrocytes
- 2016
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In: Neurochemistry International. - : Elsevier BV. - 0197-0186. ; 96, s. 13-23
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Journal article (peer-reviewed)abstract
- Bites from genus Phoneutria (Ctenidae, Araneomorpha) are the second most frequent source of spider accidents in Southeast Brazil. Severe envenoming from Phoneutria nigriventer produces vision disturbance, tremor and convulsion, suggesting that the CNS is involved; however, the mechanisms by which P. nigriventer venom (PNV) affects the CNS remain poorly understood. The present study aimed to investigate whether PNV directly impairs astrocytes. Cultured astrocytes were exposed to PNV, and intracellular Ca2+ release and signaling were measured (Fura-2/AM), Na+/K+-ATPase and Toll-like receptor 4 (TLR4) involvement were investigated, actin filaments were stained (Alexa (TM) 488-conjugated phalloidin probe), the G-actin/F-actin ratio was determined, and the expression level of connexin 43 (Cx43) was assessed. Incubation in Ca2+-free buffer did not change the Ca2+ responses. However, pre-incubation in thapsigargin/caffeine completely abolished these responses, suggesting that PNV-evoked Ca2+ transients were from intracellular Ca2+ stores. Pretreatment with a Na+/K+-ATPase antagonist (ouabain) or a TLR4 antagonist (LPS-RS) decreased or increased the Ca2+-evoked transients, respectively. Astrocytes showed altered actin filament structure after PNV exposure. PNV treatment increased the expression levels of Na+/K+-ATPase and Cx43 but decreased those of TLR4. The present results suggest that PNV directly affects astrocytes. Na+/K+-ATPase may thus represent a more specific drug target for controlling the neurotoxicity of PNV. (C) 2016 Elsevier Ltd. All rights reserved.
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| 31. |
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| 32. |
- Svennerholm, Kristina, 1981, et al.
(author)
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DNA Content in Extracellular Vesicles Isolated from Porcine Coronary Venous Blood Directly after Myocardial Ischemic Preconditioning
- 2016
-
In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
-
Journal article (peer-reviewed)abstract
- Background Extracellular vesicles (EV) are nano-sized membranous structures released from most cells. They have the capacity to carry bioactive molecules and gene expression signals between cells, thus mediating intercellular communication. It is believed that EV confer protection after ischemic preconditioning (IPC). We hypothesize that myocardial ischemic preconditioning will lead to rapid alteration of EV DNA content in EV collected from coronary venous effluent. In a porcine myocardial ischemic preconditioning model, EV were isolated from coronary venous blood before and after IPC by differential centrifugation steps culminating in preparative ultracentrifugation combined with density gradient ultracentrifugation. The EV preparation was validated, the DNA was extracted and further characterized by DNA sequencing followed by bioinformatics analysis. Porcine genomic DNA fragments representing each chromosome, including mitochondrial DNA sequences, were detected in EV isolated before and after IPC. There was no difference detected in the number of sequenced gene fragments (reads) or in the genomic coverage of the sequenced DNA fragments in EV isolated before and after IPC. Gene ontology analysis showed an enrichment of genes coding for ion channels, enzymes and proteins for basal metabolism and vesicle biogenesis and specific cardiac proteins. This study demonstrates that porcine EV isolated from coronary venous blood plasma contain fragments of DNA from the entire genome, including the mitochondria. In this model we did not find specific qualitative or quantitative changes of the DNA content in EV collected immediately after an in vivo myocardial IPC provocation. This does not rule out the possibility that EV DNA content changes in response to myocardial IPC which could occur in a later time frame.
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| 33. |
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| 34. |
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| 35. |
- Svennerholm, Kristina, 1981, et al.
(author)
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Myocardial ischemic preconditioning in a porcine model leads to rapid changes in cardiac extracellular vesicle messenger RNA content
- 2015
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In: International Journal of Cardiology Heart and Vasculature. - : Elsevier. - 2352-9067. ; 8, s. 62-67
-
Journal article (peer-reviewed)abstract
- Background: Extracellular vesicles (EVs) are thought to exert protective effects after ischemic and remote ischemic preconditioning. It is not well understood which EV content factors are most relevant for protective effects. We hypothesize that ischemic preconditioning leads to qualitative changes in EV mRNA content and quantitative changes in EV size and number.Methods: Using an in vivo porcine ischemic preconditioning model, EVs were collected from coronary venous blood, and isolated by differential ultracentrifugations. The presence and purity of EV were verified by electron microscopy and Western blot, and EV number was assessed by nanoparticle tracking analysis. The mRNA EV was identified by microarray.Results: Gene ontology analysis showed enrichment of EV mRNA coding for proteins associated with regulation of transcription, translation, extracellular matrix, morphogenic development and feeding behavior. There were 11,678 different mRNA transcripts detected in EV, where a total of 1103 was significantly increased or decreased after preconditioning, of which 638 mRNA sequences were up-regulated and/or emerged due to preconditioning. Several of them have known association with ischemic preconditioning. There was no significant difference in EV quantity or size before and after preconditioning.Conclusions: These findings demonstrate in an in vivo model that myocardial ischemic preconditioning influences the composition of mRNA in EV, including gene transcripts for proteins associated with the protective effect of ischemic preconditioning. The finding that preconditioned parental cells release EV containing mRNA that is qualitatively different from those released by non-preconditioned cells shows the importance of the external milieu on parental cell EV production.
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| 36. |
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| 37. |
- Waldenström, Anders, et al.
(author)
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Ischaemic preconditioning reduces myocardial calcium overload in coronary-occluded pig hearts shown by continuous in vivo assessment using microdialysis.
- 2012
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In: Clinical physiology and functional imaging. - Malden, MA : Wiley-Blackwell. - 1475-097X .- 1475-0961. ; 32:2, s. 133-8
-
Journal article (peer-reviewed)abstract
- During ischaemia, ATP depletion leads to insufficient fuelling for Na(+) /K(+) ATPase, decreased electrochemical potential and increased influx of calcium ions. This study demonstrated a means to assess the effects of ischaemic preconditioning (IP) on the free intracellular Ca(2+) pool during prolonged ischaemia. In a porcine myocardial ischaemia model, microdialysis (MD) was used for sampling of metabolic and injury markers in IP and non-IP (control) groups. (45) Ca(2+) was delivered in microperfusate locally to ischaemic myocardium, with distribution and uptake assessed by (45) Ca(2+) recovery in microdialysate. Cardiomyocytes in vitro were exposed to a Ca(2+) ionophore and tested for (45) Ca(2+) uptake. An accentuated myocardial calcium ion influx (observed as an increased microdialysate (45) Ca(2+) recovery in the extracellular milieu) was noted in control pigs compared with IP pigs during ischaemia. Suspended cardiomyocytes preincubated with a Ca(2+) ionophore to increase the intracellular calcium ion pool and subsequently incubated with (45) Ca(2+) , displayed lower (45) Ca(2+) uptake in cells compared with control cells not exposed to the ionophore, corroborating the idea of a strong relationship between degree of intracellular calcium overload and microdialysate (45) Ca(2+) recovery. The ischaemic insult was differentially verified by metabolic and injury markers. We introduce an in vivo method for serial assessment of myocardial calcium overload during ischaemia, using a MD technique and (45) Ca(2+) inclusion. IP leads to relatively less calcium overload as assessed by this new method, and we interpret this to mean that reduction in calcium overload is an important part of the IP protective effect.
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| 38. |
- Österlund, Barbro, et al.
(author)
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Impaired myocardial t-PA release in patients with coronary artery disease
- 2008
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In: Acta Anaesthesiol Scand. - : Wiley. - 1399-6576. ; 52:10, s. 1375-84
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Journal article (peer-reviewed)abstract
- AIMS: Myocardial ischemia remains a significant perioperative complication in coronary artery disease (CAD) patients. We hypothesized that noxious stimuli during major surgery are associated with an acute release of tissue-type plasminogen activator (t-PA) into the coronary circulation, and that this response is reduced by CAD. METHODS AND RESULTS: Two patient groups, with (n=14) and without (n=8) CAD, were studied during the initial phase of heart surgery. After retrograde great cardiac vein catheterizations during closed-chest conditions, coronary arterial-venous concentration gradients of t-PA and plasminogen activator inhibitor type-1 (PAI-1) were measured together with coronary blood flow measurements, allowing derivation of coronary net release rates. Pre-surgery atrial pacing, performed to evaluate the influence of increases in heart rate (+ 40 beats/min) and coronary blood flow (+ 80 ml/min), did not significantly alter coronary net release of t-PA or PAI-1 in either patient group. Sternotomy induced a prominent increase in coronary net release of both total and active t-PA in the non-CAD group. This response was considerably reduced in the CAD group. CONCLUSIONS: This study provides the first analysis of coronary t-PA release during major surgery and demonstrates a deficient local endothelial t-PA release in patients with CAD. This suggests a reduced local fibrinolytic capacity in CAD patients, which may explain the increased risk for coronary thrombosis in this patient group.
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