1. |
- Edvinsson, Marie Louise, et al.
(author)
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Improved outcome with standardized plan for clinical management of acute decompensated chronic heart failure
- 2019
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In: Journal of Geriatric Cardiology. - 1671-5411. ; 16:1, s. 12-18
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Journal article (peer-reviewed)abstract
- Background Our overall goal is to improve clinical care for inpatients with chronic heart failure (CHF). A retrospective assessment of CHF patients admitted to our hospital over the past decade (2005 vs. 2014) indicated a need for better strategies to evaluate clinical treatment, implement best practices and achieve optimal patient outcome. To that purpose, we developed a standardized plan to improve in-hospital treatment of acute decompensated CHF patients. Methods & Results Retrospective chart reviews were conducted to compare three cohorts of CHF patients admitted to the University Hospital of Lund at different time points over a 12-year period: 2005 (365 patients), 2014 (172 patients) and 2017–2018 (57 patients). Little improvement was seen between 2005 and 2014 with respect to one-year mortality (35% vs. 34%) and adequate treatment with recommended medications, e.g., use of renin-angiotensin system blockers (45% vs. 51%). A standardized treatment plan was devised to improve outcomes. A third cohort, treated under the plan (2017–2018), was compared with the 2014 cohort. One-year mortality (18% vs. 34%) and 30-day readmission (5% vs. 30%) were dramatically decreased, and adherence to medication guidelines was achieved. Key elements of the plan included well-defined treatment procedures, enhanced communication and teamwork, education, adequate time for treatment (5 days) and post-discharge follow-up as necessary. Natriuretic peptide (NT-proBNP) levels were useful for assessing patient status, prognosis and response to treatment. Conclusion Development of a standard plan for clinical management of acute decompensated CHF patients resulted in significant improvements in patient outcome, as reflected in decreased rates of 30-day readmission and one-year mortality.
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2. |
- Hedström, Erik, et al.
(author)
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Infarct evolution in man studied in patients with first-time coronary occlusion in comparison to different species - implications for assessment of myocardial salvage
- 2009
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In: Journal of Cardiovascular Magnetic Resonance. - 1097-6647. ; 11:38
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Journal article (peer-reviewed)abstract
- BACKGROUND: The time course of infarct evolution, i.e. how fast myocardial infarction (MI) develops during coronary artery occlusion, is well known for several species, whereas no direct evidence exists on the evolution of MI size normalized to myocardium at risk (MaR) in man. Despite the lack of direct evidence, current literature often refers to the "golden hour" as the time during which myocardial salvage can be accomplished by reperfusion therapy. Therefore, the aim of the present study was to investigate how duration of myocardial ischemia affects infarct evolution in man in relation to previous animal data. Consecutive patients with clinical signs of acute myocardial ischemia were screened and considered for enrollment. Particular care was taken to assure uniformity of the patients enrolled with regard to old MI, success of revascularization, collateral flow, release of biochemical markers prior to intervention etc. Sixteen patients were ultimately included in the study. Myocardium at risk was assessed acutely by acute myocardial perfusion single photon emission computed tomography (MPS) and by T2 imaging (T2-STIR) cardiovascular magnetic resonance (CMR) after one week in 10 of the 16 patients. Infarct size was measured by late gadolinium enhancement (LGE) at one week. RESULTS: The time to reach 50% MI of the MaR (T50) was significantly shorter in pigs (37 min), rats (41 min) and dogs (181 min) compared to humans (288 min). There was no significant difference in T50 when using MPS compared to T2-STIR (p = 0.53) for assessment of MaR (288 +/- 23 min vs 310 +/- 22 min, T50 +/- standard error). The transmural extent of MI increased progressively as the duration of ischemia increased (R2 = 0.56, p < 0.001). CONCLUSION: This is the first study to provide direct evidence of the time course of acute myocardial infarct evolution in relation to MaR in man with first-time MI. Infarct evolution in man is significantly slower than in pigs, rats and dogs. Furthermore, infarct evolution assessments in man are similar when using MPS acutely and T2-STIR one week later for determination of MaR, which significantly facilitates future clinical trials of cardioprotective therapies in acute coronary syndrome by the use of CMR.
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3. |
- Hedström, Erik, et al.
(author)
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Initial results of inflammatory response, matrix remodeling, and reactive oxygen species following PCI in acute ischemic myocardial injury in man.
- 2011
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In: Journal of Invasive Cardiology. - 1557-2501. ; 23:9, s. 371-376
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Journal article (peer-reviewed)abstract
- Background. Neutrophils and reactive oxygen species (ROS) are suggested to be involved in irreversible myocardial reperfusion injury and stunning. We investigated the relations between circulating biochemical markers and myocardium at risk (MaR), myocardial infarct (MI) size, salvage, and recovery of function in man. Methods and Results. In patients undergoing PCI serial blood samples were acquired for markers of inflammatory response (myeloperoxidase [MPO], neutrophil-gelatinase-associated lipocalin [NGAL], interleukins 6 and 8 [IL-6/8], tumor necrosis factor-α [TNF-α], high-sensitive C-reactive protein [hsCRP]), matrix remodeling (matrixmetalloproteinase-9 [MMP-9]) and ROS (malondialdehyde [MDA], isoprostane [IsoP]). Samples were obtained before PCI and 1.5, 3, and 24 hours after reperfusion. Myocardial perfusion SPECT (MPS) was used to assess MaR. Late gadolinum-enhanced cardiac magnetic resonance imaging was performed for regional function in the acute setting, at 1 week and 6 months, and at 1 week also for MI size. Sixteen patients (15 men; 42–78 years) were enrolled, 12 of whom underwent MPS. Peak and cumulative NGAL and cumulative MMP-9 showed inverse correlations to MaR. No correlation was found for MI size. Peak MPO correlated inversely to salvage and to recovery of regional function in the infarcted segments at 1 week and 6 months. Conclusions. This is the first study in man to show inverse relations between circulating NGAL and MMP-9 and MaR. The current results do not support that ROS has a role in stunning in man. MI size showed no significant correlation to any parameter, challenging inflammatory treatment in reperfusion.
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4. |
- Hedström, Erik, et al.
(author)
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Peak CKMB and cTnT accurately estimates myocardial infarct size after reperfusion
- 2007
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In: Scand Cardiovasc J.. - : Informa UK Limited. ; 41:1, s. 44-50
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To find the time-to-peak for creatine kinase MB(mass) (CKMB) and cardiac troponin T (cTnT) after acute reperfusion, to compare peak and cumulative values to estimate infarct size (IS), and to evaluate clinical routine sampling for assessment of IS. DESIGN: Acute primary percutaneous coronary intervention (PCI) was performed in 38 patients with first-time myocardial infarction. In 21 patients, CKMB and cTnT were acquired before PCI and at 1.5, 3, 6, 12, 18, 24, and 48 hours thereafter. In 17 patients, clinical routine samples were acquired at arrival, and at 10 and 20 h. IS was assessed by delayed contrast-enhanced MRI (DE-MRI). RESULTS: Time-to-peak was 7.6+/-3.6 h for CKMB and 8.1+/-3.4 h for cTnT. Peak values correlated strongly to cumulative values (r(s)=0.97-0.98) as well as to DE-MRI (r(s)=0.8-0.82). Clinical routine sampling showed lower rs values (0.47-0.60). CONCLUSIONS: Peak values are likely captured if CKMB and cTnT are acquired at 3, 6, and 12 h after acute PCI. These peak values can be used to estimate myocardial infarct size after acute PCI
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5. |
- Jonsjö, Martin A., et al.
(author)
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Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation
- 2020
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In: Brain, Behavior, & Immunity - Health. - : Elsevier BV. - 2666-3546. ; 2
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Journal article (peer-reviewed)abstract
- Background: Chronic sickness behavior is implicated in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain but the level of subjective sickness behavior in these conditions has not been investigated or compared to other clinical and non-clinical samples, or to the level in experimental inflammation. Furthermore, the relationship between sickness behavior and self-rated health and functioning is not known in patients with ME/CFS and chronic pain. The aim of the present study was to investigate how sickness behavior in patients with chronic conditions differs from that in individuals with experimental acute sickness, primary care patients, the general population and healthy subjects. In addition, we wanted to explore how sickness behavior is related to self-rated health and health-related functioning.Methods: Sickness behavior was quantified using the sickness questionnaire (SicknessQ). Self-ratings were collected at one time-point in 6 different samples. Levels of sickness behavior in patients with ME/CFS (n = 38) and patients with chronic pain (n = 190) were compared to healthy subjects with lipopolysaccharide(LPS)-induced inflammation (n = 29), primary care patients (n = 163), individuals from the general population (n = 155) and healthy subjects (n = 48), using linear regression. Correlations and moderated regression analyses were used to investigate associations between sickness behavior and self-rated health and health-related functioning in ME/CFS, chronic pain and the general population.Results: LPS-injected individuals (M = 16.3), patients with ME/CFS (M = 16.1), chronic pain (M = 16.1) and primary care patients (M = 10.7) reported significantly higher SicknessQ scores than individuals from the general population (M = 5.4) and healthy subjects (M = 3.6) all p’s < 0.001). In turn, LPS-injected individuals, patients with ME/CFS and chronic pain reported significantly higher SicknessQ scores than primary care patients (p’s < 0.01). Higher levels of sickness behavior were associated with poorer self-rated health and health-related functioning (p’s < 0.01), but less so in patients with ME/CFS and chronic pain than in individuals from the general population.Conclusions: Patients with ME/CFS and chronic pain report similar high levels of sickness behavior; higher than primary care patients, and comparable to levels in experimental inflammation. Further study of sickness behavior in ME/CFS and chronic pain populations is warranted as immune-to-brain interactions and sickness behavior may be of importance for functioning as well as in core pathophysiological processes in subsets of patients.
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6. |
- Karlsson, Lars O., et al.
(author)
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Cyclosporine does not reduce myocardial infarct size in a porcine ischemia-reperfusion model.
- 2010
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In: Journal of Cardiovascular Pharmacology and Therapeutics. - : Sage Publications. - 1074-2484 .- 1940-4034. ; 15:2, s. 182-9
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Journal article (peer-reviewed)abstract
- Cyclosporine A (CsA) has been shown to protect against myocardial ischemia and reperfusion (I/R) injury in small animal models. The aim of the current study was to evaluate the effects of CsA on myocardial I/R injury in a porcine model. Pigs were randomized between CsA (10mg/kg; n = 12) or placebo (n = 15) and anesthetized with either isoflurane (phase I) or pentobarbital (phase II). By catheterization, the left descending coronary artery was occluded for 45 minutes, followed by reperfusion for 2 hours. Hearts were stained to quantify area at risk (AAR) and infarct size (IS). Myocardial biopsies were obtained for terminal dUTP nick end labeling and immunoblot analysis of proapoptotic proteins (apoptosis-inducing factor [AIF], BCL2/adenovirus E1B 19-kd interacting protein 3 [BNIP-3], and active caspase-3). Cyclosporine A did not reduce IS/AAR compared with placebo (49% vs 41%, respectively; P = .21). Pigs anesthetized with isoflurane had lower IS/AAR than pigs anesthetized with pentobarbital (39% vs 51%, respectively; P = .03). This reduction in IS/AAR seemed to be attenuated by CsA. Apoptosis-inducing factor protein expression was higher after CsA administration than after placebo (P = .02). Thus, CsA did not protect against I/R injury in this porcine model. The data suggest a possible deleterious interaction of CsA and isoflurane.
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7. |
- Odell, Annika, 1960, et al.
(author)
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The Impact of General Usage of Stents on Short- and Long-Term Health Care Costs following Percutaneous Coronary Intervention
- 2007
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In: Cardiology. ; 109:2, s. 85-92
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Journal article (peer-reviewed)abstract
- Background: The general usage of stents during percutaneous coronary intervention (PCI) reduces the need for subsequent repeated revascularizations when compared with balloon dilatation. The aim was to evaluate the impact of stenting on short- and long-term in-hospital care costs after PCI. Method and Results: Patients who underwent PCI from July 1992 to June 1993 (group A, n = 166; 4.2% stents) and from July 1996 to June 1997 (group B, n = 233; 61.4% stents) were included. The clinical outcome and all in-hospital care costs during 2.5 years following the procedures were analyzed. During the study period the number of deaths and acute myocardial infarctions was similar in the groups, but repeated revascularization occurred more often in group A than in group B (53.6 vs. 39.5%; p = 0.007). The initial procedural cost per patient was higher in group B than in group A (EUR 7,653 +/- 5,071 vs. EUR 6,048 +/- 3,242; p = 0.002), but after 2.5 years the costs were similar in the 2 groups (not significant). Conclusion: General usage of stents increases immediate health care cost compared with balloon dilatation, but despite reduction in subsequent revascularization, there is no reduction in long-term in-hospital costs. Copyright (c) 2007 S. Karger AG, Basel.
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8. |
- Odell, Annika, et al.
(author)
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The impact of general usage of stents on short- and long-term health care costs following percutaneous coronary intervention
- 2008
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In: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 109:2, s. 85-92
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Journal article (peer-reviewed)abstract
- Background: The general usage of stents during percutaneous coronary intervention (PCI) reduces the need for subsequent repeated revascularizations when compared with balloon dilatation. The aim was to evaluate the impact of stenting on short- and long-term in-hospital care costs after PCI. Method and Results: Patients who underwent PCI from July 1992 to June 1993 (group A, n = 166; 4.2% stents) and from July 1996 to June 1997 (group B, n = 233; 61.4% stents) were included. The clinical outcome and all in-hospital care costs during 2.5 years following the procedures were analyzed. During the study period the number of deaths and acute myocardial infarctions was similar in the groups, but repeated revascularization occurred more often in group A than in group B (53.6 vs. 39.5%; p = 0.007). The initial procedural cost per patient was higher in group B than in group A (EUR 7,653 +/- 5,071 vs. EUR 6,048 +/- 3,242; p = 0.002), but after 2.5 years the costs were similar in the 2 groups (not significant). Conclusion: General usage of stents increases immediate health care cost compared with balloon dilatation, but despite reduction in subsequent revascularization, there is no reduction in long-term in-hospital costs.
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9. |
- Rosander, Ulla, 1954-, et al.
(author)
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Methodological considerations in a pilot study on the effects of a berry enriched smoothie on children's performance in school
- 2016
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In: Food & Nutrition Research. - 1654-6628 .- 1654-661X. ; 60:1
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Journal article (other academic/artistic)abstract
- Background and aims: In many countries, the consumption of fruit, berries, and vegetables is about half the recommended. Berries contain bioactive compounds that may affect cognitive functions. School children are often hungry and thirsty during the lectures before lunch and this affects performance. Could a berry-smoothie decrease thirst and hunger, and thereby affect school performance? The aim was to investigate if a cross-over design can be used to study the effects of a smoothie on performance in a school setting.Methods: Methodological challenges included developing an appetizing berry-smoothie and choosing a suitable experimental design that could be adapted to school conditions.In the pilot study, 236 Swedish children aged 10–12 years participated in a cross-over design and were administered either a berry-smoothie or a fruit-based placebo after the midmorning break. Both beverages provided 5% of the daily energy intake. Performance was assessed using the d2 Test of Attention measuring attention span and concentration. Statistical analyses were performed using the Wilcoxon signed rank test in StatXact v 10.3.Results: The consumption of both the smoothie and the placebo increased the attention span and concentration significantly.Conclusion: The children's performance in the d2 Test of Attention was positively affected by beverage consumption. The effect was attributed to the supplementation of water and energy. In this design, the study did not permit any conclusive results regarding the effect of bioactive compounds on performance. In a coming study, a third group, receiving no beverage, should be included aiming to identify the cause of the effect.
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10. |
- Rosander, Ulla, et al.
(author)
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Methodological considerations in a pilot study on the effects of a berry enriched smoothie on children’s performance in school
- 2017
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In: Food & Nutrition Research. - : Taylor & Francis. ; 61:1
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Journal article (peer-reviewed)abstract
- Berries contain bioactive compounds that may affect children’s cognitive function positively, while hunger and thirst during lessons before lunch affect academic performance negatively. This pilot study addresses methodological challenges in studying if a berry smoothie, offered to schoolchildren as a mid-morning beverage, affects academic performance.The objective was to investigate if a cross-over design can be used to study these effects in a school setting.Therefore, in order to investigate assay sensitivity, 236 Swedish children aged 10–12 years were administered either a berry smoothie (active) or a fruit-based control beverage after their mid-morning break. Both beverages provided 5% of child daily energy intake. In total, 91% of participants completed the study. Academic performance was assessed using the d2 test of attention. Statistical analyses were performed using the Wilcoxon signed rank test in StatXact v 10.3.The results showed that the children consumed less of the active berry smoothie than the control (154 g vs. 246 g). Both beverages increased attention span and concentration significantly (p = 0.000). However, as there was no significant difference (p = 0.938) in the magnitude of this effect between the active and control beverages, the assay sensitivity of the study design was not proven. The effect of the beverages on academic performance was attributed the supplementation of water and energy.Despite careful design, the active smoothie was less accepted than the control. This could be explained by un-familiar sensory characteristics and peer influence, stressing the importance of sensory similarity and challenges to perform a study in school settings. The employed cross-over design did not reveal any effects of bioactive compound consumption on academic performance. In future studies, the experimental set up should be modified or replaced by e.g. the parallel study design, in order to provide conclusive results.
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11. |
- Rosander, Ulla, et al.
(author)
-
Methodological considerations in a pilot study on the effects of a berry enriched smoothie on children’s performance in school
- 2017
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In: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 61:1
-
Journal article (peer-reviewed)abstract
- Berries contain bioactive compounds that may affect children’s cognitive function positively, while hunger and thirst during lessons before lunch affect academic performance negatively. This pilot study addresses methodological challenges in studying if a berry smoothie, offered to schoolchildren as a mid-morning beverage, affects academic performance. The objective was to investigate if a cross-over design can be used to study these effects in a school setting. Therefore, in order to investigate assay sensitivity, 236 Swedish children aged 10–12 years were administered either a berry smoothie (active) or a fruit-based control beverage after their mid-morning break. Both beverages provided 5% of child daily energy intake. In total, 91% of participants completed the study. Academic performance was assessed using the d2 test of attention. Statistical analyses were performed using the Wilcoxon signed rank test in StatXact v 10.3. The results showed that the children consumed less of the active berry smoothie than the control (154 g vs. 246 g). Both beverages increased attention span and concentration significantly (p = 0.000). However, as there was no significant difference (p = 0.938) in the magnitude of this effect between the active and control beverages, the assay sensitivity of the study design was not proven. The effect of the beverages on academic performance was attributed the supplementation of water and energy. Despite careful design, the active smoothie was less accepted than the control. This could be explained by un-familiar sensory characteristics and peer influence, stressing the importance of sensory similarity and challenges to perform a study in school settings. The employed cross-over design did not reveal any effects of bioactive compound consumption on academic performance. In future studies, the experimental set up should be modified or replaced by e.g. the parallel study design, in order to provide conclusive results.
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12. |
- Rosander, Ulla, et al.
(author)
-
Methodological considerations in a pilot study on the effects of a berry enriched smoothie on children's performance in school
- 2016
-
In: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X.
-
Conference paper (other academic/artistic)abstract
- Background and aims: In many countries, the consumption of fruit, berries, and vegetables is about half the recommended. Berries contain bioactive compounds that may affect cognitive functions. School children are often hungry and thirsty during the lectures before lunch and this affects performance. Could a berry-smoothie decrease thirst and hunger, and thereby affect school performance? The aim was to investigate if a cross-over design can be used to study the effects of a smoothie on performance in a school setting. Methods: Methodological challenges included developing an appetizing berry-smoothie and choosing a suitable experimental design that could be adapted to school conditions. In the pilot study, 236 Swedish children aged 10–12 years participated in a cross-over design and were administered either a berry-smoothie or a fruit-based placebo after the midmorning break. Both beverages provided 5% of the daily energy intake. Performance was assessed using the d2 Test of Attention measuring attention span and concentration. Statistical analyses were performed using the Wilcoxon signed rank test in StatXact v 10.3. Results: The consumption of both the smoothie and the placebo increased the attention span and concentration significantly. Conclusion: The children's performance in the d2 Test of Attention was positively affected by beverage consumption. The effect was attributed to the supplementation of water and energy. In this design, the study did not permit any conclusive results regarding the effect of bioactive compounds on performance. In a coming study, a third group, receiving no beverage, should be included aiming to identify the cause of the effect.
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13. |
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14. |
- Åström-Olsson, Karin, 1959, et al.
(author)
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Dissociation of the Inflammatory Reaction following PCI for Acute Myocardial Infarction
- 2007
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In: J Inv Cardiology. ; 19:11, s. 452-456
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Neutrophils are activated and infiltrate the myocardium after ischemia and reperfusion. The involvement of neutrophils in irreversible reperfusion injury is suggested by numerous experimental studies. The aim of this study was to investigate markers of neutrophil activation following reperfusion of acute myocardial infarction (AMI) accomplished with percutaneous coronary intervention (PCI) and their relationship to markers of lipid peroxidation, cytokines and highly-sensitive C-reactive protein (hsCRP). DESIGN: Non-consecutive patients with their first myocardial infarction were evaluated. Setting. University hospital as primary referral center, single center. PATIENTS AND METHODS: Forty-nine patients with AMI were evaluated. All were treated with primary PCI and infusion of abciximab. Reperfusion was verified by angiography. Blood samples for analyses of myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), malondialdehyde (MDA), 8-isoprostane-prostaglandin F2alpha (Iso-P), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factoralpha (TNFalpha), hsCRP, creatine kinase-monobasic fraction (CK-MB) and troponin-T (TnT) were obtained at baseline with the occluded coronary vessel, and subsequently after verified reperfusion at 1.5, 3 and 24 hours. RESULTS: Significant increases in MMP-9, IL-6, IL-8, TNFalpha and hsCRP were observed, and a significant decrease in MPO and MDA was also observed over the same period. No significant changes in Iso-P and NGAL were found. CONCLUSION: We found a dissociation of the inflammatory reaction after PCI for AMI: a decrease of markers of neutrophil activation and MDA, but an increase in cytokines and hsCRP. An antineutrophil effect of the PCI procedure including treatment with abciximab, an antiplatelet drug and a modulator of inflammation, is conceivable.
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15. |
- Åström-Olsson, Karin, 1959, et al.
(author)
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Impact of hypoxia, simulated ischemia and reperfusion in HL-1 cells on the expression of FKBP12/FKBP12.6 and intracellular calcium dynamics
- 2012
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 422:4, s. 732-738
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Journal article (peer-reviewed)abstract
- Aims: To establish a cardiac cell culture model for simulated ischemia and reperfusion and in this model investigate the impact of simulated ischemia and reperfusion on expression of the calcium handling proteins FKBP12 and FKBP12.6, and intracellular calcium dynamics. Methods: HL-1 cell cultures were exposed to normoxia (as control), hypoxia, simulated ischemia (HEDA) or HEDA + reactive oxygen species (ROS) for up to 24 h and after HEDA, with or without ROS, followed or not by simulated reperfusion (REPH) for 6 h. Viability was analyzed with a trypan blue exclusion method. Cell lysates were analyzed with real-time PCR and Western blot (WB) for FKBP12 and FKBP12.6. Intracellular Ca(2+)measurements were performed using dual-wavelength ratio imaging in fura-2 loaded cells. Results: A time-dependent drop in viability was shown after HEDA (P < 0.001). Viability was not further influenced by addition of ROS or REPH. The general patterns of FKBP12 and FKBP12.6 mRNA expression showed upregulation after hypoxia, downregulation after ischemia and normalization after reperfusion, which was partially attenuated if ROS was added during HEDA. The protein contents were unaffected after hypoxia, tended to increase after ischemia and, for FKBP12.6, a further increase after reperfusion was shown. Hypoxia or HEDA, with or without REPH, resulted in a decreased amplitude of the Ca2+ peak in response to caffeine. In addition, cells subjected to HEDA for 3 h or HEDA for 3 h followed by 6 h of REPH displayed irregular Ca2+ oscillations with a decreased frequency. Conclusion: A threshold for cell survival with respect to duration of ischemia was established in our cell line model. Furthermore, we could demonstrate disturbances of calcium handling in the sarcoplasmic reticulum as well as alterations in the expressions of the calcium handling proteins FKBP12 and FKBP12.6, why this model may be suitable for further studies on ischemia and reperfusion with respect to calcium handling of the sarcoplasmic reticulum. (C) 2012 Elsevier Inc. All rights reserved.
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16. |
- Åström-Olsson, Karin, 1959
(author)
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Myocardial ischemia and reperfusion injury, clinical and experimental studies
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Acute myocardial infarction is the consequence of an occluded nutrient coronary artery. Reperfusion reduces infarct size and enhances the rate of survival. But reperfusion may also, in itself, cause reversible injury, stunning and arrhythmias, as well as irreversible lethal reperfusion injury. The aim of this thesis was to gain knowledge about the complex pathophysiology behind myocardial reperfusion injury. Two different patient populations with AMI, treated with primary percutaneous coronary intervention were investigated. Presumptive underlying causes for reperfusion injury such as reactive oxygen species (ROS) production, neutrophil activation, signs of inflammation and myocardial cellular damage were studied. In a part of the patient population, delayed-enhanced magnetic resonance imaging (DE-MRI) was performed to estimate infarct size. An experimental porcine infarction with reperfusion was investigated, in which myocardial microdialysis samples and biopsies were analysed with proteomics, Western Blot and real-time-polymerase chain reaction. Mouse cardiomyocytes (HL-1 cells) were analysed after exposition to hypoxia. The HL-1 cells were further investigated with aspects of FKBP12 and FKBP12.6 release in hypoxia, energy depletion, acidosis, ROS activation and re-establishing of physiologic conditions, simulating ischemia and reperfusion at varying durations. Markers for inflammation increased over time, whereas the markers for ROS production and neutrophil activation were at the maximum level at baseline and during the first day. Biomarkers, showing myocardial injury, were useful for infarct size estimation compared with DE-MRI when obtained correctly. FKBP12 and FKBP12.6, increased during ischemia/hypoxia in both the experimental models. Viability of HL-1 cells matched severity of duration and intensity of ischemia. FKBP12 and FKBP12.6 increased during simulated ischemia, while the mRNA expression was depressed suggesting dissociation from receptors regulating intracellular calcium flows. Clinical symptoms and signs of reperfusion injury may partly be explained by release of FKBP12 and FKBP12.6, this causing disturbance of the intracellular cell contraction. These findings may indicate further important mechanisms in ischemia/hypoxia and reperfusion in the heart.
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17. |
- Åström-Olsson, Karin, 1959, et al.
(author)
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Myocardial release of FKBP12 and increased production of FKBP12.6 in ischemia and reperfusion experimental models
- 2009
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In: Biochem Biophys Res Commun. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 390:4, s. 1299-304
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Journal article (peer-reviewed)abstract
- BACKGROUND: Coronary artery occlusion and reperfusion may trigger reversible and irreversible ischemic and reperfusion injury. The primary aim of this study was to evaluate protein release into the myocardium in a porcine model during ischemia and reperfusion to search for clarifying models for reperfusion injury and secondarily to investigate release and production of the immunophilins FKBP12/12.6 in this model and in cell cultures. METHODS: In a porcine model local myocardial ischemia was induced during 45min followed by 120min of reperfusion. Microdialysis samples from ischemic and non-ischemic areas were analyzed with surface-enhanced laser desorption ionization (SELDI) mass spectrometry (MS) and Western blotting (WB). Myocardial biopsies from areas at risk and control areas were analyzed with reverse transcription polymerase chain reaction (RT-PCR). Myocardial cell cultures from mice (HL-1 cells) were exposed to hypoxia and then analyzed with WB and RT-PCR. RESULTS: FK binding protein12 (FKBP12), ubiquitin and myoglobin were identified as being released during ischemia and reperfusion in microdialysates. RT-PCR analysis on the biopsies after ischemia revealed a non-significant increase in mRNA expression of FKBP12 and a significant increase in mRNA expression of FKBP12.6. Lysates from HL-1 cells exposed to hypoxia demonstrated increase of FKBP12 and a significant increase in mRNA expression of FKBP12.6. CONCLUSION: In a myocardial ischemic-reperfusion porcine model as well as in hypoxic HL-1 cells, release of FKBP12 and increased production of FKBP12.6 was demonstrated. The findings indicate important mechanisms related to these immunophilins in the reaction to ischemia/hypoxia and reperfusion in the heart.
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