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- Danielsson, Christian, et al.
(författare)
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Exploration of human, rat, and rabbit embryonic cardiomyocytes suggests K-channel block as a common teratogenic mechanism
- 2013
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP): Policy B. - 0008-6363 .- 1755-3245. ; 97:1, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- Several drugs blocking the rapidly activating potassium (K-r) channel cause malformations (including cardiac defects) and embryonic death in animal teratology studies. In humans, these drugs have an established risk for acquired long-QT syndrome and arrhythmia. Recently, associations between cardiac defects and spontaneous abortions have been reported for drugs widely used in pregnancy (e.g. antidepressants), with long-QT syndrome risk. To investigate whether a common embryonic adverse-effect mechanism exists in the human, rat, and rabbit embryos, we made a comparative study of embryonic cardiomyocytes from all three species. less thanbrgreater than less thanbrgreater thanPatch-clamp and quantitative-mRNA measurements of K-r and slowly activating K (K-s) channels were performed on human, rat, and rabbit primary cardiomyocytes and cardiac samples from different embryo-foetal stages. The K-r channel was present when the heart started to beat in all species, but was, in contrast to human and rabbit, lost in rats in late organogenesis. The specific K-r-channel blocker E-4031 prolonged the action potential in a species- and development-dependent fashion, consistent with the observed K-r-channel expression pattern and reported sensitive periods of developmental toxicity. E-4031 also increased the QT interval and induced 2:1 atrio-ventricular block in multi-electrode array electrographic recordings of rat embryos. The K-s channel was expressed in human and rat throughout the embryo-foetal period but not in rabbit. less thanbrgreater than less thanbrgreater thanThis first comparison of mRNA expression, potassium currents, and action-potential characteristics, with and without a specific K-r-channel blocker in human, rat, and rabbit embryos provides evidence of K-r-channel inhibition as a common mechanism for embryonic malformations and death.
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- Szummer, Karolina, et al.
(författare)
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Relationship of plasma erythropoietin to long-term outcome in acute coronary syndrome
- 2010
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 143:2, s. 165-170
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Erythropoietin has been related to adverse prognosis in patients with heart failure, but it is unknown whether it adds prognostic information in acute coronary syndrome. METHODS: Plasma erythropoietin was measured on admission with enzyme-linked immunosorbent assay in 627 patients. Patients were divided into three groups depending on their erythropoietin level and followed for myocardial infarction (MI) (median 6 months) and mortality (median 39 months). Cox regression models were used to evaluate erythropoietin compared to clinical variables; age, gender, diabetes, smoking, prior MI, heart failure, hypertension and revascularization. In a second Cox regression model, laboratory markers were assessed; hemoglobin, estimated glomerular filtration rate (eGFR), C-reactive protein (CRP), cardiac troponin T (cTnT) and N-terminal pro-brain-natriuretic peptide (NT-proBNP). RESULTS: Patients with the highest erythropoietin level (>8.8 mU/mL, n=205) had a 47% increased mortality (HR 1.47, 95% CI 1.04-2.06, p=0.028) when adjusted for clinical variables. Compared to laboratory risk markers, erythropoietin added prognostic information (HR 1.59, 95% CI 1.05-2.38, p=0.027) when adjusted for hemoglobin, eGFR and CRP. Erythropoietin (HR 1.21, 95% CI 0.79-1.86, p=0.387) was no longer significantly associated with mortality when cTnT and NT-proBNP were added. Erythropoietin was not related to the risk of future MI (HR 1.24, 95% CI 0.65-2.33, p=0.513). CONCLUSION: Elevated erythropoietin level was associated with increased mortality in patients admitted with possible ACS when adjusted for clinical variables, or for kidney function and hemoglobin. However, erythropoietin does not add prognostic information when markers of myocardial necrosis and dysfunction are available in ACS.
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