| 61. |
- Aljassim, Obaid, et al.
(författare)
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Inflammatory response and platelet activation after off-pump coronary artery bypass surgery.
- 2006
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Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 40:1, s. 43-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cardiac surgery induces a systemic inflammatory activation and alterations in the hemostatic cascade. The responses contribute to postoperative complications but may also have protective effects. We investigated the relationship between inflammation, hemostasis and bleeding after off-pump coronary artery bypass surgery (OPCAB). METHODS: Ten OPCAB patients were included in a prospective descriptive study. Selected markers of inflammation (IL-6, IL-8, PMN-elastase, C3a, and SC5b-9), and hemostasis (platelet count, ss-thromboglobulin, anti-thrombin, D-dimer and fibrinogen) were measured before and immediately after surgery. Postoperative bleeding was registered. RESULTS: Inflammatory variables did not alter significantly during surgery while ss-thromboglobulin concentrations increased and anti-thrombin and fibrinogen decreased. There were significant postoperative correlations between PMN-elastase and ss-thromboglobulin (r=0.82, p=0.004), between PMN-elastase and fibrinogen (r=0.69, p=0.03) and between C3a and ss-thromboglobulin (r=0.71, p=0.02). In addition, there were significant inverse correlations between postoperative bleeding and pre- and postoperative fibrinogen levels (r=-0.76, p=0.011 and r=-0.84, p=0.002 respectively), between bleeding and postoperative ss-thromboglobulin levels (r=-0.66, p=0.04) and between bleeding and postoperative PMN-elastase (r=-0.75, p=0.01). CONCLUSIONS: The results give further evidence for an association between the inflammatory response and hemostasis after cardiac surgery.
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| 62. |
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| 63. |
- Andersson, Linda, 1973, et al.
(författare)
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Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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| 64. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
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Effects of fibrinogen and platelet supplementation on clot formation and platelet aggregation in blood samples from cardiac surgery patients.
- 2014
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Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 134:4, s. 895-900
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Tidskriftsartikel (refereegranskat)abstract
- Bleeding after cardiac surgery may be caused by surgical factors, impaired haemostasis, or a combination of both. Transfusion of blood products is used to improve haemostasis, but little is known about what combination is optimal. We hypothesized that addition of both fibrinogen and platelets to blood samples from cardiac surgery patients would improve clot formation and platelet aggregation to a greater extent than if the components were added separately.
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| 65. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
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Effects of fibrinogen and platelet transfusion on coagulation and platelet function in bleeding cardiac surgery patients.
- 2019
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Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 63:4, s. 475-482
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Tidskriftsartikel (refereegranskat)abstract
- Excessive bleeding is a significant problem in cardiac surgery. Fibrinogen and platelet concentrate transfusion are used clinically to improve haemostasis and reduce bleeding but little is known about their functional effects on coagulation and platelet function in patients with ongoing bleeding.Forty-two patients with ongoing bleeding after cardiac surgery were included in an observational study. Patients received either fibrinogen concentrate (n=16), platelet concentrate (n=12), or both fibrinogen and platelets (n=14), median doses 2g fibrinogen and 2 units platelets given at one occasion. Blood samples were collected before and after transfusion. Coagulation (clotting time and clot stability) was analysed with rotational thromboelastometry, and platelet function with impedance aggregometry. In addition, platelet count and fibrinogen concentration was measured. Chest drain output was measured before and after the transfusion.Fibrinogen infusion resulted in an increase in fibrinogen concentration and clot stability (P=0.001), but had no effect on platelet aggregation. Platelet transfusion did not significantly affect coagulation, but improved arachidonic acid- and TRAP-induced platelet aggregation (P=0.017 and 0.034 respectively) and increased platelet count. Combined fibrinogen and platelet transfusion shortened clotting time (P=0.005) and increased clot stability (P=0.001), and improved arachidonic acid- and TRAP-induced platelet aggregation (P=0.004 and 0.016 respectively), and increased fibrinogen concentration and platelet count. The median bleeding volume was 150 (25th-75th percentile 70-240)mL/h before, and 60 (40-110)mL/h after transfusion of fibrinogen and/or platelet concentrate (P<0.001).The results demonstrate improved coagulation and platelet function following fibrinogen and platelet transfusion in patients bleeding after cardiac surgery.
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| 66. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
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In vitro assessment of platelet concentrates with multiple electrode aggregometry.
- 2015
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Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 26:2, s. 132-137
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Storage impairs platelet function. It was hypothesized that multiple electrode aggregometry in vitro could be used to follow aggregability in platelet concentrates over time and that the results predict the efficacy of platelet transfusion in an ex vivo transfusion model. In vitro platelet aggregability was assessed in apheresis and pooled buffy coat platelet concentrates (BCs) (n = 13 each) using multiple electrode aggregometry with different agonists 1, 3, 5 and 7 days after preparation. In the ex vivo transfusion model, whole blood samples from nine healthy volunteers were collected every second day. The samples were supplemented with stored platelets (+146 × 10(9) × l(-1)) from the same unit 1, 3, 5 and 7 days after preparation. Platelet aggregability was assessed in the concentrate and in the whole blood samples before and after platelet supplementation. There was a continuous reduction in in vitro platelet aggregability over time in both apheresis and pooled BCs. The same pattern was observed after ex vivo addition of apheresis and pooled BCs to whole blood samples. The best correlation between in vitro aggregability and changes in aggregation after addition was achieved with collagen as agonist (r = 0.67, p
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| 67. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
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The Effect of Ex Vivo Factor XIII Supplementation on Clot Formation in Blood Samples From Cardiac and Scoliosis Surgery Patients.
- 2018
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Ingår i: Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. - : SAGE Publications. - 1938-2723. ; 24:4, s. 677-683
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Tidskriftsartikel (refereegranskat)abstract
- Excessive perioperative bleeding remains a substantial problem. Factor XIII (FXIII) contributes to clot stability, and it has therefore been suggested that supplementation with FXIII concentrate may improve perioperative hemostasis. We evaluated the effects of increasing doses of FXIII, alone or in combination with fibrinogen or platelet concentrate, in blood samples from 2 considerably different groups of surgical patients: cardiac and scoliosis surgery patients. Whole-blood samples were collected immediately after operation from cardiac and scoliosis surgery patients. The samples were supplemented with 3 clinically relevant doses of FXIII concentrate (+20%, +40%, and +60%), alone or in combination with a fixed dose of fibrinogen concentrate (+1.0 g/L) or fresh apheresis platelets (+92 × 10(9)/L). Clot formation was assessed with rotational thromboelastometry (ROTEM). When the highest dose of FXIII concentrate was added, EXTEM clotting time was shortened by 10% in both cardiac and scoliosis surgery patients (95% confidence intervals: 2.4%-17% and 3.3%-17%, respectively), and FIBTEM maximum clot firmness was increased by 25% (9.3%-41%) in cardiac patients, relative to baseline. When fibrinogen was added, the dose-dependent effect of FXIII on clot stability was maintained, but the total effect was markedly greater than with FXIII alone, +150% (100%-200%) and +160% (130%-200%) for the highest FXIII dose in cardiac and scoliosis patients, respectively. Ex vivo supplementation with clinically relevant doses of FXIII improved clot formation moderately in blood samples from cardiac and scoliosis surgery patients, both alone and when given in combination with fibrinogen or platelet concentrate.
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| 68. |
- Anttila, V., et al.
(författare)
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Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting
- 2023
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0016. ; 31:3, s. 866-874
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%–50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool. © 2022
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| 69. |
- Anttila, V., et al.
(författare)
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Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial
- 2020
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Ingår i: Molecular Therapy-Methods & Clinical Development. - : Elsevier BV. - 2329-0501. ; 18, s. 464-472
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic angiogenesis may improve outcomes in patients with coronary artery disease undergoing surgical revascularization. Angiogenic factors may promote blood vessel growth and regenerate regions of ischemic but viable myocardium. Previous clinical trials of vascular endothelial growth factor A (VEGF-A) gene therapy with DNA or viral vectors demonstrated safety but not efficacy. AZD8601 is VEGF-A(165) mRNA formulated in biocompatible citrate-buffered saline and optimized for high-efficiency VEGF-A expression with minimal innate immune response. EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30% 50%) undergoing elective coronary artery bypass surgery. AZD8601 3 mg, 30 mg, or placebo is administered as 30 epicardial injections in a 10-min extension of cardioplegia. Injections are targeted to ischemic but viable myocardial regions in each patient using quantitative O-15-water positron emission tomography (PET) imaging (stress myocardial blood flow < 2.3 mL/g/min; resting myocardial blood flow > 0.6 mL/g/min). Improvement in regional and global myocardial blood flow quantified with O-15-water PET is an exploratory efficacy outcome, together with echocardiographic, clinical, functional, and biomarker measures. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887).
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| 70. |
- Asp, Julia, 1973, et al.
(författare)
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Comparison of human cardiac gene expression profiles in paired samples of right atrium and left ventricle collected in vivo
- 2012
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 44:1, s. 89-98
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Tidskriftsartikel (refereegranskat)abstract
- Studies of expressed genes in human heart provide insight into both physiological and pathophysiological mechanisms. This is of importance for extended understanding of cardiac function as well as development of new therapeutic drugs. Heart tissue for gene expression studies is generally hard to obtain, particularly from the ventricles. Since different parts of the heart have different functions, expression profiles should likely differ between these parts. The aim of the study was therefore to compare the global gene expression in cardiac tissue from the more accessible auricula of the right atrium to expression in tissue from the left ventricle. Tissue samples were collected from five men undergoing aortic valve replacement or coronary artery bypass grafting. Global gene expression analysis identified 542 genes as differentially expressed between the samples extracted from these two locations, corresponding to similar to 2% of the genes covered by the microarray; 416 genes were identified as abundantly expressed in right atrium, and 126 genes were abundantly expressed in left ventricle. Further analysis of the differentially expressed genes according to available annotations, information from curated pathways and known protein interactions, showed that genes with higher expression in the ventricle were mainly associated with contractile work of the heart. Transcription in biopsies from the auricula of the right atrium on the other hand indicated a wider area of functions, including immunity and defense. In conclusion, our results suggest that biopsies from the auricula of the right atrium may be suitable for various genetic studies, but not studies directly related to muscle work.
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