| 1. |
- Lennmyr, Fredrik, et al.
(författare)
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Cerebral effects of hyperglycemia in experimental cardiac arrest
- 2010
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 38:8, s. 1726-1732
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the effects of cardiac arrest on cerebral perfusion and oxidative stress during hyperglycemia and normoglycemia. Design: Experimental animal model. Setting: University laboratory. Subjects: Triple-breed pigs (weight, 22-27 kg). Interventions: Thirty-three pigs were randomized and clamped at blood glucose levels of 8.5-10 mM (high) or 4-5.5 mM (normal) and thereafter subjected to alternating current-induced 12-min cardiac arrest followed by 8 mins of cardiopulmonary resuscitation and direct-current shock to restore spontaneous circulation. Measurements and Main Results: Hemodynamics, regional near-infrared light spectroscopy, regional venous HbO(2), and biochemical markers (Protein S100 beta, troponin I, F-2-isoprostanes reflecting oxidative stress and inflammation) were monitored and/or sampled throughout an observation period of 4 hrs. No significant differences were seen in hemodynamics or biochemical profile. The cerebral oxygenation by means of regional near-infrared light spectroscopy was higher in the hyperglycemic (H) than in the normal (N) group after restoration of spontaneous circulation (p < .05). However, tendencies toward increased protein S100 beta and 15-keto-dihydro-prostaglandin F-2 alpha were observed in the H group but were not statistically significant. Conclusions: The responses to 12-min cardiac arrest and cardiopulmonary resuscitation share large similarities during hyperglycemia and normoglycemia. The higher cerebral tissue oxygenation observed in the hyperglycemia needs to be confirmed and the phenomenon needs to be addressed in future studies.
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| 2. |
- Lindblom, Rickard P F, 1981-, et al.
(författare)
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Hyperglycemia Alters Expression of Cerebral Metabolic Genes after Cardiac Arrest
- 2018
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057 .- 1532-8511. ; 27:5, s. 1200-1211
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Tidskriftsartikel (refereegranskat)abstract
- Background: Survivors of cardiac arrest often experience neurologic deficits. To date, treatment options are limited. Associated hyperglycemia is believed to further worsen the neurologic outcome. The aim with this study was to characterize expression pathways induced by hyperglycemia in conjunction with global brain ischemia.Methods: Pigs were randomized to high or normal glucose levels, as regulated by glucose and insulin infusions with target levels of 8.5-10 mM and 4-5.5 mM, respectively. The animals were subjected to 5-minute cardiac arrest followed by 8 minutes of cardiopulmonary resuscitation and direct-current shock to restore spontaneous circulation. Global expression profiling of the cortex using microarrays was performed in both groups.Results: A total of 102 genes differed in expression at P<.001 between the hyperglycemic and the normoglycemic pigs. Several of the most strongly differentially regulated genes were involved in transport and metabolism of glucose. Functional clustering using bioinformatics tools revealed enrichment of multiple biological processes, including membrane processes, ion transport, and glycoproteins.Conclusions: Hyperglycemia during cardiac arrest leads to differential early gene expression compared with normoglycemia. The functional relevance of these expressional changes cannot be deduced from the current study; however, the identified candidates have been linked to neuroprotective mechanisms and constitute interesting targets for further studies.
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| 3. |
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| 4. |
- Molnar, Maria, et al.
(författare)
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Hyperglycaemia increases S100β after short experimental cardiac arrest
- 2014
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 58:1, s. 106-113
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Hyperglycaemia is associated with aggravated ischaemic brain injury. The main objective of this study was to investigate the effects on cerebral perfusion of 5 min of cardiac arrest during hyperglycaemia and normoglycaemia.METHODS:Twenty triple-breed pigs (weight: 22-29 kg) were randomised and clamped at blood glucose levels of 8.5-10 mM [high (H)] or 4-5.5 mM [normal (N)] and thereafter subjected to alternating current-induced 5 min-cardiac arrest followed by 8 min of cardiopulmonary resuscitation and direct current shock to restore spontaneous circulation.RESULTS:Haemodynamics, laser Doppler measurements and regional venous oxygen saturation (HbO2 ) were monitored, and biochemical markers in blood [S100β, interleukin (IL)-6 and tumour necrosis factor (TNF)] quantified throughout an observation period of 3 h. The haemodynamics and physiological measurements were similar in the two groups. S100β increased over the experiment in the H compared with the N group (P < 0.05). IL-6 and TNF levels increased across the experiment, but no differences were seen between the groups.CONCLUSIONS:The enhanced S100β response is compatible with increased cerebral injury by hyperglycaemic compared with normoglycaemic 5 min of cardiac arrest and resuscitation. The inflammatory cytokines were similar between groups.
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| 5. |
- Zoerner, Frank, et al.
(författare)
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Milrinone and esmolol decrease cardiac damage after resuscitation from prolonged cardiac arrest
- 2015
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 59:4, s. 465-474
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Tidskriftsartikel (refereegranskat)abstract
- Background: Long-term survival after cardiac arrest (CA) due to shock-refractory ventricular fibrillation (VF) is low. Clearly, there is a need for new pharmacological interventions in the setting of cardiopulmonary resuscitation (CPR) to improve outcome. Here, hemodynamic parameters and cardiac damage are compared between the treatment group (milrinone, esmolol and vasopressin) and controls (vasopressin only) during resuscitation from prolonged CA in piglets.Methods: Twenty-six immature male piglets were subjected to 12 min VF followed by 8 min CPR. The treatment group (n=13) received i.v. boluses vasopressin 0.4 U∙kg−1, esmolol 250 μg∙kg−1 and milrinone 25 μg∙kg−1 after 13 min, followed by i.v. boluses esmolol 375 μg∙kg−1 and milrinone 25 μg∙kg−1 after 18 min and continuous esmolol 15 μg∙kg−1∙h−1 infusion during 180 min reperfusion, while controls (n=13) received equal amounts of vasopressin and saline. A 200J monophasic counter-shock was delivered to achieve resumption of spontaneous circulation (ROSC) after 8 min CPR. If ROSC was not achieved, another 200J defibrillation and bolus vasopressin 0.4 U∙kg−1 were administered in both groups. DC shocks at 360J were applied as one shot min−1 over maximally 5 min. Hemodynamic variables and troponin I as a marker of cardiac injury were recorded.Results: Troponin I levels after 180 min reperfusion were lower in the treatment group than in controls (p<0.05). The treatment group received less norepinephrine (p<0.01) and had greater diuresis (p<0.01). There was no difference in survival between groups.Conclusions: The combination of milrinone, esmolol and vasopressin decreased cardiac injury compared with vasopressin alone.
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| 6. |
- Zoerner, Frank, 1973-
(författare)
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Novel Interventions in Cardiac Arrest : Targeted Temperature Management, Methylene Blue, S-PBN, Amiodarone, Milrinone and Esmolol, Endothelin and Nitric Oxide In Porcine Resuscitation Models
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is a major clinical problem that survival rates after out-of-hospital cardiac arrest have not markedly improved during the last decades, despite extensive research and the introduction of new interventions. However, recent studies have demonstrated promising treatments such as targeted temperature management (TTM) and methylene blue (MB).In our first study, we investigated the effect of MB administered during experi-mental cardiopulmonary resuscitation (CPR) in the setting of postponed hypother-mia in piglets. We set out to study if MB could compensate for a delay to establish targeted TTM. The study demonstrated that MB more than compensated for 30 min delay in induction of TTM. The effect of MB added to that of TTM.The second study examined the effects of TTM and S-PBN on the endothelin system and nitric oxide synthases (NOS) after prolonged CA in a porcine CPR mod-el. The study was designed to understand the cardioprotective mechanism of S-PBN and TTM by their influence on the endothelin system and NOS regulation. We veri-fied for the first time, that these two cardioprotective postresuscitative interventions activate endothelin-1 and its receptors concomitantly with eNOS and nNOS in the myocardium. We concluded that nitric oxide and endothelin pathways are implicated in the postresuscitative cardioprotective effects of TTM.The third study compared survival and hemodynamic effects of low-dose amio-darone and vasopressin to vasopressin in a porcine hypovolemic CA model. The study was designed to evaluate whether resuscitation with amiodarone and vasopressin compared to vasopressin alone would have an impact on resuscitation success, survival, and hemodynamic parameters after hemorrhagic CA. We found that combined resuscitation with amiodarone and vasopressin after hemorrhagic circulatory arrest resulted in greater 3-hour survival, better preserved hemodynamic parameters and smaller myocardial injury compared to resuscitation with vasopressin only.In our fourth study we planned to compare hemodynamic parameters between the treatment group (milrinone, esmolol and vasopressin; MEV) and control group (vasopressin only) during resuscitation from prolonged cardiac arrest in piglets. The study was designed to demonstrate if MEV treatment improved hemodynamics or cardiac damage compared to controls. We demonstrated that MEV treatment reduced cardiac injury compared with vasopressin alone.
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