A5057582462- Adenosine and Purinergic Signaling
- Nitric Oxide and Endothelin Effects
- Advanced MRI Techniques and Applications
- Cardiac Ischemia and Reperfusion
- Cardiac Imaging and Diagnostics
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Function and Risk Factors
- Electron Spin Resonance Studies
- Cardiac Fibrosis and Remodeling
- Ion channel regulation and function
- Hemoglobin structure and function
- Receptor Mechanisms and Signaling
- Mechanical Circulatory Support Devices
- Eicosanoids and Hypertension Pharmacology
- Renin-Angiotensin System Studies
- Cardiac Arrhythmias and Treatments
- Congenital heart defects research
- Adipose Tissue and Metabolism
- Lanthanide and Transition Metal Complexes
- Signaling Pathways in Disease
- Tissue Engineering and Regenerative Medicine
- Macrophage Migration Inhibitory Factor
- Neuroscience and Neuropharmacology Research
- Peptidase Inhibition and Analysis
- Immune Cell Function and Interaction
Heinrich Heine University Düsseldorf
2015-2024
Düsseldorf University Hospital
2006-2024
Wayne State University
2016
Detroit R&D (United States)
2016
Center for Anti-Slavery Studies
2016
Biotronik (Germany)
2010-2015
St. Josefs Hospital
2009-2015
St. Josefs-Hospital Cloppenburg
2012
St. Joseph Hospital
2010
University of Virginia Health System
2010
A specific difference-spectrophotometric method was used to measure nitric oxide (NO) release into the coronary effluent perfusate of isolated, constant-flow-perfused guinea pig hearts. Authentic NO applied circulation decreased vascular resistance dose dependently and enhanced cyclic GMP (cGMP) fivefold. Increasing oxygen tension in aqueous solutions from 150 700 mm Hg half-life (5.6 seconds) by 32%. During single passage through intact system, 86% infused converted nitrite ions. Oxidation...
To determine half-life and turnover of plasma adenosine, heparinized blood from healthy volunteers was incubated with radiolabeled adenosine in the physiological concentration range 0.1-1 microM. Plasma levels vitro were 82 +/- 14 nM similar to those determined immediately after collection a "stopping solution." Dipyridamole (83 microM) erythro-9(2-hydroxynon-3yl)-adenine (EHNA) (8 did not measurably alter basal but completely blocked uptake added adenosine. Inhibition ecto-5'-nucleotidase...
The present study explored the role of myoglobin (Mb) in cardiac NO homeostasis and its functional relevance by employing isolated hearts wild-type (WT) knockout mice. 1 H NMR spectroscopy was used to measure directly conversion oxygenated Mb (MbO 2 ) metmyoglobin (metMb) reaction with NO. applied intracoronarily (5 nM 25 μM), or endogenous production stimulated bradykinin (Bk; 10 μM). We found that infusion authentic solutions dose-dependently (≥ 2.5 μM NO) increased metMb formation WT...
The nitrite anion is reduced to nitric oxide (NO*) as oxygen tension decreases. Whereas this pathway modulates hypoxic NO* signaling and mitochondrial respiration limits myocardial infarction in mammalian species, the pathways bioactivation remain uncertain. Studies suggest that hemoglobin myoglobin may subserve a fundamental physiological function hypoxia dependent reductases. Using wild-type ((+/+)) knockout ((-/-)) mice, we here test central role of functional reductase regulates...
In this study, we developed and validated a new approach for in vivo visualization of inflammatory processes by magnetic resonance imaging using biochemically inert nanoemulsions perfluorocarbons (PFCs).Local inflammation was provoked 2 separate murine models acute cardiac cerebral ischemia, followed intravenous injection PFCs. Simultaneous acquisition morphologically matching proton ((1)H) fluorine ((19)F) images enabled an exact anatomic localization PFCs after application. Repetitive...
Background— HMG-CoA reductase inhibitors, such as simvastatin, have been shown to exhibit pronounced immunomodulatory effects independent of lipid lowering but date not used treat severe inflammatory disease sepsis. We thus approached the question whether treatment with simvastatin might improve cardiovascular function and survival in Methods Results— Mice treated rendered septic by cecal ligation perforation (CLP) show a mean time close 4 times value found untreated mice. This dramatic...
Background— HMG-CoA-reductase inhibitors have been shown to exhibit pronounced immunomodulatory effects independent of lipid lowering. We recently demonstrated that pretreatment with simvastatin profoundly improves survival in a cecal ligation and perforation (CLP) model sepsis. Here, we studied whether treatment after onset sepsis-induced hemodynamic alterations is beneficial prolonged can also be achieved other statins. Methods Results— Mice were rendered septic by CLP. At 6 hours sepsis...
Although the primary function of myoglobin (Mb) has been considered to be cellular oxygen storage and supply, recent studies have suggested classify Mb as a multifunctional allosteric enzyme. In heart, acts potent scavenger nitric oxide (NO) contributes attenuation oxidative damage. Here we report that dynamic cycle exists in which decrease tissue tension drives conversion from being an NO normoxia producer hypoxia. The generated by reaction deoxygenated with nitrite is functionally relevant...
Myoglobin may serve a variety of functions in muscular oxygen supply, such as O 2 storage, facilitated diffusion, and myoglobin-mediated oxidative phosphorylation. We studied the functional consequences myoglobin deficiency on cardiac function by producing myoglobin-knockout (myo −/− ) mice. To genetically inactivate gene, exon encoding heme binding site was deleted embryonic stem cells via homologous recombination. Myo mice are viable, fertile, without any obvious signs limitations....
Abstract —For the specific analysis of endothelial NO synthase (eNOS) function in coronary vasculature, we generated a mouse homozygous for defective eNOS gene (eNOS−/−). Western blot as well immunohistochemical staining revealed absence protein eNOS−/− mice. Aortic cells derived from mice displayed only background levels x formation compared with wild-type (WT) (88 versus 1990 pmol · h −1 /mg ). were hypertensive (mean arterial pressure, 135±15 107±8 mm Hg WT) without development cardiac...
Abstract To elucidate the physiological role of AMP-adenosine metabolic cycle and to investigate relation between AMP adenosine formation, O 2 supply isolated guinea pig hearts was varied (95% 10% ). The net formation rate (AMP→adenosine) coronary venous effluent release were measured; free cytosolic determined by 31 P-nuclear magnetic resonance. Switching from 95% 40% increased 4-fold, whereas rose 15- 20-fold. In range 200 3000 nmol/L, there a linear correlation ( R =.71); however,...
To investigate the role of adenosine formed extracellularly in vascular homeostasis, mice with a targeted deletion cd73/ecto-5'-nucleotidase were generated. Southern blot, RT-PCR, and Western blot analysis confirmed constitutive knockout. In vivo hemodynamic parameters revealed no significant differences systolic blood pressure, ejection fraction, or cardiac output between strains. However, basal coronary flow measured isolated perfused heart was significantly lower (-14%; P<0.05) mutant....
Two noninvasive methods, calorimetry and 31P nuclear magnetic resonance (NMR), were used to further define energy-consuming energy-providing reactions in endothelial cells. With 31P-NMR, cellular ATP content was measured; with calorimetry, heat flux as a result of turnover measured. For these measurements, pig aortic cells cultured on microcarrier beads perfused column at constant flow rate. Pig synthesize mainly through glycolysis and, determined by NMR, contain no phosphocreatine. In such...
Taurine is the most abundant free amino acid in heart and skeletal muscle. In present study, effects of hereditary taurine deficiency on muscle function were examined transporter knockout (taut-/-) mice. These mice show an almost complete depletion levels. Treadmill experiments demonstrated that total exercise capacity taut-/- was reduced by >80% compared with wild-type controls. The decreased performance correlated increased lactate levels serum during exercise. Surprisingly, cardiac as...
To evaluate the role of nitric oxide (NO) in flow response after brief coronary arterial occlusion, NO formation by isolated guinea pig heart was assessed a specific difference spectrophotometric assay. Release under basal conditions 121.8 +/- 10.5 pmol x min-1 and increased to 211.1 16.8 60 seconds occlusion. Simultaneously, release cGMP adenosine 87% 652%, respectively. The kinetics paralleled reactive hyperemic response. Inhibition synthesis with nitro-L-arginine methyl ester (L-NAME, 30...
To investigate the basic mechanism for formation of adenosine, cardiac work was increased using an isolated guinea pig working heart preparation. Cardiac metabolism stimulated by intracoronary infusion isoproterenol, norepinephrine (NE), ouabain, and cardiotonic agent 1H-imidazo[4,5-b]pyridine, 2-[2-methoxy-4-(methylsulfinyl)-phenyl] (AR-L 115), release adenosine into effluent determined. Besides their inotropic effects on myocardial tissue, these substances affect differently tone coronary...
In an attempt to further define the site of myocardial adenosine formation, isolated guinea pig hearts were perfused with potent inhibitors 5'-nucleotidase [alpha, beta-methylene 5'-diphosphate (AOPCP)] and nucleoside transport [4-nitrobenzyl thioinosine (NBMPR)]. AOPCP (50 microM) inhibited activity cardiac ecto-5'-nucleotidase by 85% but did not influence release adenosine, inosine, hypoxanthine formed at accelerated rate heart during hypoxic perfusion (30% O2). contrast, NBMPR (5...
Inflammatory processes can reliably be assessed by 19F MRI using perfluorocarbons (PFCs), which is primarily based on the efficient uptake of emulsified PFCs circulating cells monocyte–macrophage system and subsequent infiltration 19F-labeled into affected tissue. An ideal candidate for sensitive detection fluorine-loaded biochemically inert perfluoro-15-crown-5 ether (PFCE), as it contains 20 magnetically equivalent atoms. However, biological half-life PFCE in liver spleen extremely long,...
CD73-derived adenosine acts as potent inhibitor of inflammation, and regulatory T cells (Treg) have been shown to express CD73 a novel marker. This study explored the role endogenously formed in modulating NF-κB activity cytokine/chemokine release from murine Treg effector (Teff) including key enzymes/purinergic receptors extracellular ATP catabolism. Stimulating splenocytes CD4 + with anti-CD3/anti-CD28 significantly upregulated activated −/− (wild type: 4.36 ± 0.21; : 6.58 0.75; n = 4; P...