Publications (19) View all
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Article: Dexrazoxane prevents the development of the impaired cardiac phenotype in Caveolin-1 disrupted mice.
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ABSTRACT: Caveolin-1 deficient mice (cav1) display a severely diseased cardiac phenotype with systolic and diastolic heart failure. Accumulating evidence supports a causative role of uncoupled endothelial nitric oxide synthase in the development of these abnormalities. Interestingly, a similar molecular mechanism was proposed for anthracycline-induced cardiomyopathy. Currently, dexrazoxane is approved for the prevention of anthracycline-induced cardiomyopathy. Given the molecular similarities between the anthracycline-induced cardiomyopathy and the cardiomyopathy in cav1, we questioned whether dexrazoxane may also prevent the evolution of the cardiac pathologies in cav1.We evaluated dexrazoxane-treatment for 6 weeks in cav1mice and wild type controls. The present study provides the first evidence for a reduced reactive oxygen species (ROS) formation in vessels of dexrazoxane-treated cav1 . This reduced oxidative stress resulted in a markedly reduced rate of apoptosis, which finally translated into a significantly improved heart function in dexrazoxane-treated cav1. These hemodynamic improvements were accompanied by a significantly lowered proANP levels. Notably, these protective properties of dexrazoxane were not evident in WT animals.Taken together these novel findings indicate that dexrazoxane significantly reduces vascular ROS formation cav1. Since this is paralleled by an improved cardiac performance in cav1our data suggest dexrazoxane as a novel therapeutic strategy in this specific cardiomyopathy.Journal of cardiovascular pharmacology 03/2013; · 2.83 Impact Factor -
Article: Uncoupled eNOS annihilates neuregulin-1β-induced cardioprotection: a novel mechanism in pharmacological postconditioning in myocardial infarction.
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ABSTRACT: Myocardial infarct size can be limited by pharmacological postconditioning (pPC) with cardioprotective agents. Cardioprotective effects of neuregulin-1β (NRG) via activation of protein kinase B (Akt) and downstream pathways like endothelial nitric oxide synthase (eNOS) have been postulated based on results from cell culture experiments. The purpose of this study was to investigate if eNOS may be involved in pPC with NRG. NRG application in an ex vivo mouse model (C57Bl6) of ischemia-reperfusion injury was analyzed. Unexpectedly, the infarct size increased when NRG was infused starting 5 min prior to reperfusion, even though protective Akt and GSK3β phosphorylation were enhanced. In eNOS deficient mice, however, NRG significantly reduced the infarct size. Co-infusion of NRG and L-arginine (Arg) lead to a reduction in infarct size in wild type animals. Electron paramagnetic resonance measurements revealed that NRG treatment prior to reperfusion leads to an enhanced release of reactive oxygen species compared to controls and this effect is blunted by co-infusion of Arg. This study documents the cardioprotective mechanisms of NRG signaling to be mediated by GSK3β inactivation. This is the first study to show that this protection fails in situations with dysfunctional eNOS. In eNOS deficient mice NRG exerts its protective effect via the GSK3β pathway, suggesting that the eNOS can limit cardioprotection. As dysfunctional eNOS has been described in cardiovascular risk factors like diabetes, hypertension, and hypercholesterolemia these findings can help to explain lack of postconditioning performance in models of cardiovascular co-morbidities.Molecular and Cellular Biochemistry 10/2012; · 2.06 Impact Factor -
Article: Amiodarone induced interatrial electrical dissociation mimics restored sinus rhythm in patient with persistent left atrial flutter.
Heart (British Cardiac Society) 03/2012; 98(10):830. · 4.22 Impact Factor -
Article: Tophaceous gout and renal insufficiency: a new solution for an old therapeutic dilemma.
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ABSTRACT: The prevalence of gout is increasing with increased life expectancy. Approximately half of the patients with gout have some degree of renal impairment. If both conditions persistently coexist, and in severe tophaceous gout, in particular, treatment has been difficult. We here report on the case of an 87-year-old woman, who had been suffering from recurrent gouty arthritis over 4 years. Monthly polyarthritis attacks were accompanied by subcutaneous tophi. Serum uric acid levels were constantly above 600 μmol/L (10 mg/dL). Allopurinol was no option because of intolerance, while benzbromarone was ineffective because of renal impairment. Therefore, the novel xanthin oxidase inhibitor febuxostat was started, achieving rapid control of serum urate levels (<360 μmol/L). After initial worsening of inflammation in the first weeks, gouty attacks stopped and all tophi resolved within the following 10 months. Renal function remained stable.Case Reports in Medicine 01/2011; 2011:397646. -
Article: Correlation of heart-type fatty acid-binding protein with mortality and echocardiographic data in patients with pulmonary embolism at intermediate risk.
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ABSTRACT: The management strategy in patients presenting with pulmonary embolism at intermediate risk still remains controversial. Our aim was to determine the role of heart-type fatty acid-binding protein (H-FABP) in this patient population. One hundred one consecutive patients with confirmed pulmonary embolism and echocardiographic signs of right ventricular overload but without evidence for hypotension or shock, referred to as pulmonary embolism at intermediate risk, were included in the study. Heart-type fatty acid-binding protein and other biomarkers were measured in all patients upon arrival in the emergency department. Of the included 101 patients, 14 had positive H-FABP tests. Ten patients with positive H-FABP (71%) had clinical deterioration during the hospital course and required inotropic support and 8 of these patients died. None of the 87 patients with a negative test worsened or needed inotropic support or died during hospital stay (P < .005). In the H-FABP-positive group, right ventricular function on echocardiography was more impaired (tricuspid annular plane systolic excursion 13 +/- 4 vs 18 +/- 4 mm, RV/LV ratio 1.1 +/- 0.2 vs 0.9 +/- 0.2, presence of paradoxical septal movement 79% vs 46%, presence of McConnell sign 100% vs 60%, respectively, all P < .05) compared to the H-FABP-negative group. After adjusting for potential confounding parameters, in multivariate analysis, H-FABP was the only independent predictor of mortality. Heart-type fatty acid-binding protein significantly predicts mortality in patients with pulmonary embolism at intermediate risk. Furthermore, it is significantly associated with impaired right ventricular function and shows better correlation with mortality than troponin I. It may be a novel prognostic parameter enabling the optimization of management strategy in the very difficult population of pulmonary embolism at intermediate risk.American heart journal 08/2010; 160(2):294-300. · 4.65 Impact Factor
