| 1. |
- Andersson, Henrik, et al.
(författare)
-
Assaying cardiac biomarkers for toxicity testing using biosensing and cardiomyocytes derived from human embryonic stem cells
- 2010
-
Ingår i: JOURNAL OF BIOTECHNOLOGY. - : Elsevier Science B.V., Amsterdam.. - 0168-1656 .- 1873-4863. ; 150:1, s. 175-181
-
Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem cell (hESC) derived cardiomyocytes are in the present study being used for testing drug-induced cardiotoxicity in a biosensor set-up. The design of an in vitro testing alternative provides a novel opportunity to surpass previous methods based on rodent cells or cell lines due to its significantly higher toxicological relevance. In this report we demonstrate how hESC-derived cardiomyocytes release detectable levels of two clinically decisive cardiac biomarkers, cardiac troponin T and fatty acid binding protein 3, when the cardiac cells are exposed to the well-known cardioactive drug compound. doxorubicin. The release is monitored by the immuno-biosensor technique surface plasmon resonance, particularly appropriate due to its capacity for parallel and high-throughput analysis in complex media.
|
|
| 2. |
- Asp, Julia, 1973, et al.
(författare)
-
Cardiomyocyte clusters derived from human embryonic stem cells share similarities with human heart tissue.
- 2010
-
Ingår i: Journal of molecular cell biology. - : Oxford University Press (OUP). - 1759-4685 .- 1674-2788. ; 2:5, s. 276-83
-
Tidskriftsartikel (refereegranskat)abstract
- Cardiotoxicity testing is a key activity in the pharmaceutical industry in order to detect detrimental effects of new drugs. A reliable human in vitro model would both be beneficial in selection of lead compounds and be important for reducing animal experimentation. However, the human heart is a complex organ composed of many distinct types of cardiomyocytes, but cardiomyocyte clusters (CMCs) derived from human embryonic stem cells could be an option for a cellular model. Data on functional properties of CMCs demonstrate similarities to their in vivo analogues in human. However, development of an in vitro model requires a more thorough comparison of CMCs to human heart tissue. Therefore, we directly compared individually isolated CMCs to human fetal, neonatal, adult atrial and ventricular heart tissues. Real-time qPCR analysis of mRNA levels and protein staining of ion channels and cardiac markers showed in general a similar expression pattern in CMCs and human heart. Moreover, a significant decrease in beat frequency was noted after addition of Zatebradine, a blocker to I(f) involved in regulation of spontaneous contraction in CMCs. The results underscore the similarities of CMCs to human cardiac tissue, and further support establishment of novel cardiotoxicity assays based on the CMCs in drug discovery.
|
|
| 3. |
- Esguerra, Maricris, 1981, et al.
(författare)
-
Intravital fluorescent microscopic evaluation of bacterial cellulose as scaffold for vascular grafts.
- 2010
-
Ingår i: Journal of biomedical materials research. Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 93:1, s. 140-9
-
Tidskriftsartikel (refereegranskat)abstract
- Although commonly used synthetic vascular grafts perform satisfactorily in large caliber blood vessels, they are prone to thrombosis in small diameter vessels. Therefore, small vessels might benefit from tissue engineered vascular grafts. This study evaluated bacterial cellulose (BC) as a potential biomaterial for biosynthetic blood vessels. We implanted the dorsal skinfold chambers in three groups of Syrian golden hamsters with BC (experimental group), polyglycolic acid, or expanded polytetrafluorethylene (control groups). Following implantation, we used intravital fluorescence microscopy, histology, and immunohistochemistry to analyze the biocompatibility, neovascularization, and incorporation of each material over a time period of 2 weeks. Biocompatibility was good in all groups, as indicated by the absence of leukocyte activation upon implantation. All groups displayed angiogenic response in the host tissue, but that response was highest in the polyglycolic acid group. Histology revealed vascularized granulation tissue surrounding all three biomaterials, with many proliferating cells and a lack of apoptotic cell death 2 weeks after implantation. In conclusion, BC offers good biocompatibility and material incorporation compared with commonly used materials in vascular surgery. Thus, BC represents a promising new biomaterial for tissue engineering of vascular grafts.
|
|
| 4. |
- Jernberg, Tomas, et al.
(författare)
-
The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)
- 2010
-
Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 96:20, s. 1617-1621
-
Tidskriftsartikel (refereegranskat)abstract
- Aims The aims of the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) are to support the improvement of care and evidence-based development of therapy of coronary artery disease (CAD). Interventions To provide users with online interactive reports monitoring the processes of care and outcomes and allowing direct comparisons over time and with other hospitals. National, regional and county-based reports are publicly presented on a yearly basis. Setting Every hospital (n=74) in Sweden providing the relevant services participates. Launched in 2009 after merging four national registries on CAD. Population Consecutive acute coronary syndrome (ACS) patients, and patients undergoing coronary angiography/angioplasty or heart surgery. Includes approximately 80 000 new cases each year. Startpoints On admission in ACS patients, at coronary angiography in patients with stable CAD. Baseline data 106 variables for patients with ACS, another 75 variables regarding secondary prevention after 12-14 months, 150 variables for patients undergoing coronary angiography/angioplasty, 100 variables for patients undergoing heart surgery. Data capture Web-based registry with all data registered online directly by the caregiver. Data quality A monitor visits approximately 20 hospitals each year. In 2007, there was a 96% agreement. Endpoints and linkages to other data Merged with the National Cause of Death Register, including information about vital status of all Swedish citizens, the National Patient Registry, containing diagnoses at discharge for all hospital stays in Sweden and the National Registry of Drug prescriptions recording all drug prescriptions in Sweden. Access to data Available for research by application to the SWEDEHEART steering group.
|
|
| 5. |
- Jonsson, Marianne, 1962, et al.
(författare)
-
Novel 3D culture system with similarities to the human heart for studies of the cardiac stem cell niche.
- 2010
-
Ingår i: Regenerative medicine. - : Future Medicine Ltd. - 1746-076X .- 1746-0751. ; 5:5, s. 725-36
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: The aim of this study was to develop a 3D culture system with similarities to the human heart, which was suitable for studies of adult cardiac stem or progenitor cells. MATERIALS & METHODS: Dissociated cells from human cardiac biopsies were placed in high-density pellet cultures and cultured for up to 6 weeks. Gene and protein expressions, analyzed by quantitative real-time PCR and immunohistochemistry, and morphology were studied in early and late pellets. RESULTS: Cells cultured in the 3D model showed similarities to human cardiac tissue. Moreover, markers for cardiac stem and progenitor cells were also detected after 6 weeks of culture, in addition to markers for signaling pathways active in stem cell niche regulation. CONCLUSIONS: The described 3D culture model could be a valuable tool when studying the influence of different compounds on proliferation and differentiation processes in cardiac stem or progenitor cells in cardiac regenerative research.
|
|
| 6. |
- Marberg, Helene, et al.
(författare)
-
Postoperative autotransfusion of mediastinal shed blood does not influence haemostasis after elective coronary artery bypass grafting.
- 2010
-
Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X. ; 38:6, s. 767-72
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The rationale of using autotransfusion of mediastinal shed blood after cardiac surgery is to preserve haemoglobin levels and reduce the need for allogenic blood transfusions. However, the method is controversial and its clinical value has been questioned. We hypothesised that re-transfusion of mediastinal shed blood instead impairs haemostasis after routine coronary artery bypass grafting and thus increases postoperative bleeding. METHODS: Seventy-seven consecutive elective coronary artery bypass surgery patients (mean age 67±9 years, 77% men) were included in a prospective, randomised controlled study. The patients were randomised to postoperative re-transfusion of mediastinal shed blood (n=39) or to a group where mediastinal shed blood was discarded (n=38). Primary end point was bleeding during the first 12 postoperative hours. Secondary end points were postoperative transfusion requirements, haemoglobin levels, thrombo-elastometric variables and plasma concentrations of interleukin-6, thrombin-anti-thrombin complex and D-dimer. RESULTS: Mean re-transfused volume in the autotransfusion group was 282±210 ml. There was no difference in postoperative bleeding (median 394 ml (interquartile range 270-480) vs 385 (255-430) ml, p=0.69), proportion of patients receiving transfusions of blood products (11/39 vs 11/38, p=0.95), haemoglobin levels 24h after surgery (116±13 vs 116±14 g l(-1), p=0.87), thrombo-elastometric variables, interleukin-6 (219±144 vs 201±144 pg ml(-1), p=0.59), thrombin-anti-thrombin complex (11.0±9.1 vs 14.8±15, p=0.19) or D-dimer (0.56±0.49 vs 0.54±0.44, p=0.79) between the autotransfusion group and the no-autotransfusion group. CONCLUSIONS: Autotransfusion of small-to-moderate amounts of mediastinal shed blood does not influence haemostasis after elective coronary artery bypass grafting.
|
|
| 7. |
- Perrotta, Sossio, 1975, et al.
(författare)
-
Survival and quality of life after aortic root replacement with homografts in acute endocarditis.
- 2010
-
Ingår i: The Annals of thoracic surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 90:6, s. 1862-7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Treatment of prosthetic aortic valve endocarditis and native aortic valve endocarditis with abscess formation is associated with high mortality and morbidity. Aortic root replacement with a freestanding aortic homograft is an attractive alternative. We report outcome and quality of life after homograft replacement for infective endocarditis. METHODS: Sixty-two patients with infective prosthetic valve endocarditis (n = 31) or native valve endocarditis with abscess (n = 31), operated with homograft replacement were included. Thirty-day mortality, severe operative complications (dialysis, stroke, pacemaker implantation, myocardial infarction, and prolonged mechanical ventilation), midterm survival, reoperations, and quality of life were assessed after a mean follow-up of 37 ± 11 months. RESULTS: Nine patients (15%) died within 30 days and 22 patients (35%) had severe perioperative complications. Preoperative and perioperative variables univariately associated with early mortality were higher (Cleveland Clinic risk score [p = 0.014], extracorporeal circulation time [p = 0.003], prolonged inotropic support [p = 0.03], reoperation for bleeding [p = 0.01], and perioperative myocardial infarction [p < 0.001].) Cumulative survival was 82%, 78%, 75%, and 67% at one, three, five, and ten years, respectively. One patient was reoperated due to recurrence of endocarditis nine months after surgery and one after five years due to homograft failure. Quality of life, as assessed by the 36 item short-form health survey scales for physical and mental health, was not significantly different to an age-matched and gender-matched healthy control group. CONCLUSIONS: Severe acute aortic endocarditis treated with homograft replacement is still associated with a substantial early complication rate and mortality. Long-term survival and quality of life are satisfactory in patients surviving the immediate postoperative period.
|
|
| 8. |
- Sandstedt, Joakim, et al.
(författare)
-
C-kit+ CD45- cells found in the adult human heart represent a population of endothelial progenitor cells.
- 2010
-
Ingår i: Basic research in cardiology. - : Springer Science and Business Media LLC. - 1435-1803 .- 0300-8428. ; 105:4, s. 545-56
-
Tidskriftsartikel (refereegranskat)abstract
- Although numerous reports support the existence of stem cells in the adult heart, few studies have been conducted using human cardiac tissue. Therefore, cells from human cardiac atrial biopsies were analyzed regarding progenitor properties. Expression of stem cell markers was analyzed using fluorescence-activated cell sorting. This identified a small population of C-kit+ cells, which could be further subdivided based on expression of CD45. The C-kit+ CD45+ population was determined to be of mast cell identity, while the C-kit+ CD45- population expressed mRNA of the endothelial lineage. Since the number of cells obtainable from biopsies was limited, a comparison between directly isolated and monolayer and explant cultured cells, respectively, was carried out. While both cultures retained a small population of mast cells, only monolayer culture produced a stable and relatively high percentage of C-kit+ CD45- cells. This population was found to co-express endothelial progenitor cell markers such as CD31, CD34, CXCR4, and FLK-1. The mRNA expression profile was similar to the one from directly isolated cells. When sorted cells were cultured in endothelial differentiation medium, the C-kit+ CD45- population retained its expression of endothelial markers to a large extent, but downregulated progenitor markers, indicating further differentiation into endothelial cells. We have confirmed that the human cardiac atrium contains a small C-kit+ CD45- population expressing markers commonly found on endothelial progenitor cells. The existence of an endothelial progenitor population within the heart might have future implications for developing methods of inducing neovascularization after myocardial infarction.
|
|
| 9. |
|
|
| 10. |
- Ternström, Lisa, 1972, et al.
(författare)
-
Plasma activity of individual coagulation factors, hemodilution and blood loss after cardiac surgery: a prospective observational study.
- 2010
-
Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 126:2
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hemodilution and consumption of coagulation factors during cardiopulmonary bypass has been suggested to contribute to bleeding complications after cardiac surgery. The aim was to describe the activity of individual coagulation factors after CABG in relation to hemodilution and postoperative bleeding. MATERIALS AND METHODS: Plasma concentrations of fibrinogen and plasma activity of FII, FV, FVII, FVIII, FIX, FX, FXI and FXIII adjusted for hemodilution were analysed in 57 CABG patients before, and 2h and 24h after surgery. Postoperative bleeding was registered and correlations to coagulation factor activity were calculated. RESULTS: Adjusted plasma concentration of fibrinogen (-14+/-6%), and plasma activity of FII (-9+/-6%), FV (-13+/-8%), FX (-13+/-7%) and FXIII (-9+/-14%) were reduced two hours after surgery compared to baseline (all p<0.001). FVII (+3+/-12%, p=0.34) and FXI (+1+/-19%, p=0.50) were unchanged, while FVIII (+23+/-44%, p=0.006) and FIX (+23+/-17%, p<0.001) increased. Twenty-four hours after surgery fibrinogen (+45+/-27%), FVIII (+93+/-66%) and FIX (+33+/-26%) were all increased (all p<0.001), while FVII (-37+/-14%, p<0.001), FXI (-4+/-18%, p=0.02) and FXIII (-6+/-15%, p=0.004) were decreased. Median postoperative blood loss was 380 ml/12h. There were significant inverse correlations between postoperative blood loss and fibrinogen concentration 2h after surgery (r=-0.33, p=0.019) and between postoperative blood loss and pre- and postoperative FXIII activity (r=-0.34, p=0.009 and r=-0.41, p=0.003, respectively), but not between blood loss and any of the other factors. CONCLUSIONS: There is a marked dissociation in plasma activity of individual coagulation factors after CABG. Plasma concentration of fibrinogen and factor XIII activity correlates inversely to postoperative blood loss after CABG.
|
|
