| 1. |
- Basu, Samar, et al.
(författare)
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Development of a novel biomarker of free radical damage in reperfusion injury after cardiac arrest
- 2000
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Ingår i: FEBS Letters. - 0014-5793 .- 1873-3468. ; 470:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- In a porcine model of cardiopulmonary resuscitation (CPR), we investigated changes in the plasma levels of 8-iso-PGF(2alpha), a marker for oxidative injury, and 15-keto-dihydro-PGF(2alpha), an inflammatory response indicator during the post-resuscitation period after cardiac arrest. Twelve piglets were subjected to either 2 or 5 min (VF2 and VF5 group) of ventricular fibrillation (VF) followed by 5 min of closed-chest CPR. Six piglets without cardiac arrest were used as controls. In VF5 group, 8-iso-PGF(2alpha) in the jugular bulb plasma (draining the brain) increased four-fold. Jugular bulb 8-iso-PGF(2alpha) in the control group remained unchanged. The 15-keto-dihydro-PGF(2alpha) also increased four-fold in the VF5 group. Thus, 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) measurements in jugular bulb plasma may be used as biomarkers for quantification of free radical catalyzed oxidative brain injury and inflammatory response in reperfusion injury
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| 2. |
- Basu, Samar, et al.
(författare)
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Evidence for Time-dependent Maximum Increase ofFree Radical Damage and Eicosanoid Formation in theBrain as Related to Duration of Cardiac Arrest andCardio-pulmonary Resuscitation
- 2003
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Ingår i: Free radical research. - : Informa UK Limited. - 1071-5762 .- 1029-2470. ; 37:3, s. 251-256
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Tidskriftsartikel (refereegranskat)abstract
- Recovery of neurological function in patients following cardiac arrest and cardiopulmonary resuscitation (CPR) is a complex event. Free radical induced oxidative stress is supposed to be involved in this process. We studied levels of 8-iso-PGF2alpha (indicating oxidative injury) and 15-keto-dihydro-PGF2alpha (indicating inflammatory response) in venous plasma obtained from the jugular bulb in a porcine model of experimental cardiopulmonary resuscitation (CPR) where 2, 5, 8, 10 or 12 min of ventricular fibrillation (VF) was followed by 5 or 8 min of closed-chest CPR. A significant increase of 8-iso-PGF2alpha was observed immediately following restoration of spontaneous circulation in all experiments of various duration of VF and CPR. No such increase was seen in a control group. When compared between the groups there was a duration-dependent maximum increase of 8-iso-PGF2alpha which was greatest in animals subjected to the longest period (VF12 min + CPR8 min) of no or low blood flow. In contrast, the greatest increase of 15-keto-dihydro-PGF2alpha was observed in the 13 min group (VF8 min + CPR5 min). Thus, a time-dependent cerebral oxidative injury occurs in conjunction which cardiac arrest and CPR.
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| 3. |
- Johansson, Jakob, et al.
(författare)
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Antithrombin administration during experimental cardiopulmonary resuscitation
- 2004
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 62:1, s. 71-78
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether antithrombin (AT) administration during cardiopulmonary resuscitation (CPR) increased cerebral circulation and reduced reperfusion injury. METHODS: Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, CPR was started. The animals were randomised into two groups. The treatment group received AT (250 U/kg) and the control group received placebo, after 7 min of CPR. Defibrillation was attempted after 9 min of CPR. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h. Cortical cerebral blood flow was measured using laser-Doppler flowmetry. Cerebral oxygen extraction was calculated to reflect the relation between global cerebral circulation and oxygen demand. Measurements of eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)), AT, thrombin-antithrombin complex (TAT) and soluble fibrin in jugular bulb plasma were performed to detect any signs of cerebral oxidative injury, inflammation and coagulation. RESULTS: There was no difference between the groups in cortical cerebral blood flow, cerebral oxygen extraction, or levels of eicosanoids, TAT or soluble fibrin in jugular bulb plasma after ROSC. In the control group reduction of AT began 15 min after ROSC and continued throughout the entire observation period (P < 0.05). Eicosanoids and TAT were increased compared to baseline in all animals (P < 0.01). CONCLUSIONS: In this experimental model of CPR, AT administration did not increase cerebral circulation or reduce reperfusion injury after ROSC.
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| 4. |
- Johansson, Jakob, et al.
(författare)
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Antithrombin reduction after experimental cardiopulmonary resuscitation
- 2003
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Ingår i: Resuscitation. - 0300-9572 .- 1873-1570. ; 59:2, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether activation of coagulation and inflammation during cardiac arrest results in a reduction of antithrombin (AT) and an increase in thrombin-antithrombin (TAT) complex during reperfusion.METHODS: Ventricular fibrillation (VF) was induced in ten anaesthetized pigs. After a 5-min non-intervention interval, closed-chest cardiopulmonary resuscitation (CPR) was performed for 9 min before defibrillation was attempted. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h and repeated blood samples were taken for assay of AT, TAT and eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)).RESULTS: AT began to decrease 15 min after ROSC and the reduction continued throughout the observation period (P<0.05). The lowest mean value (79%) occurred 60 min after ROSC. The TAT level was increased during the first 3 h after ROSC (P<0.05), indicating thrombin generation. The eicosanoids were increased throughout the observation period (P<0.05).CONCLUSIONS: AT is reduced and TAT and eicosanoids are increased after cardiac arrest, indicating activation of coagulation and inflammation.
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| 5. |
- Johansson, Jakob, et al.
(författare)
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Increased cortical cerebral blood flow by continuous infusion of epinephrine during experimental cardiopulmonary resuscitation
- 2003
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Ingår i: Resuscitation. - 0300-9572 .- 1873-1570. ; 57:3, s. 299-307
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the effects of continuously administered adrenaline (epinephrine), compared to bolus doses, on the dynamics of cortical cerebral blood flow during experimental cardiopulmonary resuscitation (CPR), and after restoration of spontaneous circulation (ROSC).METHODS: Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, closed-chest CPR was started. The animals were randomised into two groups. One group received three boluses of adrenaline (20 microg/kg) at 3-min intervals. The other group received an initial bolus of adrenaline (20 microg/kg) followed by an infusion of adrenaline (10 microg/kg x min). After 9 min of CPR, defibrillation was attempted, and if spontaneous circulation was achieved the adrenaline infusion was stopped. Cortical cerebral blood flow was measured continuously using Laser-Doppler flowmetry. Jugular bulb oxygen saturation was measured to reflect global cerebral oxygenation. Repeated measurements of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) in jugular bulb plasma were performed to evaluate cerebral oxidative injury.RESULTS: During CPR mean cortical cerebral blood flow was significantly higher (P=0.009) with a continuous adrenaline infusion than with repeated bolus doses. Following ROSC there was no significant difference in cortical cerebral blood flow between the two study groups. No differences in coronary perfusion pressure, rate of ROSC, jugular bulb oxygen saturation or 8-iso-PGF(2alpha) were seen between the study groups.CONCLUSIONS: Continuous infusion of adrenaline (10 microg/kg x min) generated a more sustained increase in cortical cerebral blood flow during CPR as compared to intermittent bolus doses (20 microg/kg every third minute). Thus, continuous infusion might be a more appropriate way to administer adrenaline as compared to bolus doses during CPR.
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| 6. |
- Liu, X. L., et al.
(författare)
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Differences in cerebral reperfusion and oxidative injury after cardiac arrest in pigs
- 2003
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 47:8, s. 958-967
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: An investigation of the free radical scavenger sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) and the weak vasodilatator Tris buffer mixture (TBM) on cerebral cortical blood flow (CCBF) and the jugular bulb concentration of two eicosanoids, indicators of oxidative stress and inflammation, was undertaken in 30 anaesthetized piglets during cardiopulmonary resuscitation (CPR) and after restoration of spontaneous circulation (ROSC).METHODS: Thirty animals were subjected to 8 min of untreated circulatory arrest followed by 8 min of closed-chest CPR. During CPR, the animals were randomized to receive 60 mg/kg S-PBN, 1 mmol/kg TBM or 2 ml/kg normal saline (n = 10 in each group). Systemic haemodynamic variables, CCBF and jugular bulb plasma concentrations of 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha were measured.RESULTS: The CCBF during reperfusion after ROSC was greater in the TBM group than in the S-PBN group, the regression coefficient between CCBF and mean arterial blood pressure being lower in the S-PBN group than in the TBM group. The jugular bulb plasma concentration of 8-iso-PGF2alpha during the first 30 min after ROSC was greater in the TBM group than in the S-PBN group. Administration of TBM after vasopressin did not attenuate the pressor effect of vasopressin.CONCLUSION: Administration of S-PBN during CPR results in less cerebral oxidative stress, possibly by promoting normal distribution of cerebral blood flow.
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| 7. |
- Liu, X. L., et al.
(författare)
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Neurological outcome after experimental cardiopulmonary resuscitation : a result of delayed and potentially treatable neuronal injury?
- 2002
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 46:5, s. 537-546
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In experimental cardiopulmonary resuscitation (CPR) aortic balloon occlusion, vasopressin, and hypertonic saline dextran administration improve cerebral blood flow. Free radical scavenger alpha-phenyl-N-tert-butyl-nitrone (PBN) and cyclosporine-A (CsA) alleviate neuronal damage after global ischemia. Combining these treatments, we investigated neurological outcome after experimental cardiac arrest.METHODS: Thirty anesthetized piglets, randomly allocated into three groups, were subjected to 8 min of ventricular fibrillation followed by 5 min of closed-chest CPR. The combined treatment (CT) group received all the above-mentioned modalities; group B was treated with balloon occlusion and epinephrine; and group C had sham balloon occlusion with epinephrine. Indicators of oxidative stress (8-iso-PGF(2 alpha)), inflammation (15-keto-dihydro-PGF(2 alpha)), energy crisis (hypoxanthine and xanthine), and anoxia/hypoxia (lactate) were monitored in jugular bulb venous blood. Neurological outcome was evaluated 24 h after CPR.RESULTS: Restoration of spontaneous circulation (ROSC) was more rapidly achieved and neurological outcome was significantly better in the CT group, although there was no difference in coronary perfusion pressure between groups. The jugular venous PCO2 and cerebral oxygen extraction ratio were lower in the CT group at 5-15 min after ROSC. Jugular venous 8-iso-PGF(2 alpha) and hypoxanthine after ROSC were correlated to 24 h neurological outcomeCONCLUSIONS: A combination of cerebral blood flow promoting measures and administration of alpha-phenyl-N-tert-butyl-nitrone and cyclosporine-A improved 24 h neurological outcome after 8 min of experimental normothermic cardiac arrest, indicating an ongoing neuronal injury in the reperfusion phase.
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| 8. |
- Semenas, Egidijus, et al.
(författare)
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Sex differences in cerebral injury after severe haemorrhage and ventricular fibrillation in pigs
- 2010
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 54:3, s. 343-353
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Tidskriftsartikel (refereegranskat)abstract
- Background: Experimental studies of haemorrhagic shock have documented a superior haemodynamic response and a better outcome in female animals as compared with male controls. Such sexual dimorphism has, nevertheless, not been reported after circulatory arrest that follows exsanguination and shock. We aimed to study differences in cerebral injury markers after exsanguination cardiac arrest in pre-pubertal piglets. The hypothesis was that cerebral injury is less extensive in female animals, and that this difference is independent of sexual hormones or choice of resuscitative fluid. Methods: Thirty-two sexually immature piglets (14 males and 18 females) were subjected to 5 min of haemorrhagic shock followed by 2 min of ventricular fibrillation and 8 min of cardiopulmonary resuscitation, using three resuscitation fluid regimens (whole blood, hypertonic saline and dextran, or acetated Ringers' solution plus whole blood and methylene blue). Haemodynamic values, cellular markers of brain injury and brain histology were studied. Results: After successful resuscitation, female piglets had significantly greater cerebral cortical blood flow, tended to have lower S-100beta values and a lower cerebral oxygen extraction ratio. Besides, in female animals, systemic and cerebral venous acidosis were mitigated. Female piglets exhibited a significantly smaller increase in neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in their cerebral cortex, smaller blood-brain-barrier (BBB) disruption and significantly smaller neuronal injury. Conclusion: After resuscitation from haemorrhagic circulatory arrest, cerebral reperfusion is greater, and BBB permeability and neuronal injury is smaller in female piglets. An increased cerebral cortical iNOS and nNOS expression in males implies a mechanistic relationship with post-resuscitation neuronal injury and warrants further investigation.
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