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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The adrenergic receptors of rat pineal gland were investigated using radiolabeled ligand binding and photoaffinity labeling techniques. 125I-2-[β-(4-hydroxyphenyl)ethylaminomethyl]tetralone (125I-HEAT) and 125I-cyanopindolol (125I-CYP) labeled specific sites on rat pineal gland membranes with equilibrium dissociation constants (KD) of 48 (±5) pM and 30 (±5) pM, respectively. Binding site maxima were 481 (±63) and 1,020 (±85) fmol/mg protein. The sites labeled by 125I-HEAT had the pharmacological characteristics of α1-adrenergic receptors. 125I-CYP-labeled β-adrenergic receptors were characterized as a homogeneous population of β1-adrenergic receptors. The α1- and β1-adrenergic receptors were covalently labeled with the specific photoaffinity probes 4-amino-6,7-dimethoxy-2-{4-[5-(4-azido-3-[125I]iodo-phenyl) pentanoyl]-1-piperazinyl}quinazoline (125I-APDQ) and 125I-p-azidobenzylcarazolol (125I-pABC). 125I-APDQ labeled an α1-adrenergic receptor peptide of Mr= 74,000 (±4,000), which was similar to peptides labeled in rat cerebral cortex, liver, and spleen. 125I-pABC labeled a single β1-adrenergic receptor peptide with a Mr= 42,000 (±1,500), which differed from the 60–65,000 peptide commonly seen in mammalian tissues. Possible reasons for these differences are discussed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
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    Pacing and clinical electrophysiology 27 (2004), S. 0 
    ISSN: 1540-8159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: AF leads to electrophysiological changes, but it is not known if similar alterations also appear before the onset of the first episode of AF because invasive electrophysiological studies are not justified in otherwise symptom-free patients. To address this question requires a safe method of obtaining atrial electrophysiological parameters at no extra risk or discomfort for the patient. The aim of this study was to test if recording of monophasic action potentials (MAPs) is feasible during pacemaker implantation. The study included 22 patients undergoing pacemaker implantation for symptomatic bradycardia without any history of AF. Using a custommade amplifier and a minor modification of the routine procedure for intraoperatively measured P waves, atrial electrograms could be recorded using a standard active pacemaker lead. MAP-like electrograms were obtained in 15 patients. MAP amplitude was 2.6 ± 0.3 mV, mean action potential duration was 316 ± 12 ms at a spontaneous heart rate of 67.2 ± 3.2 beats/min. MAP duration was decreased when atria were stimulated at shorter cycle lengths (249 ± 12 ms at 150 beats/min, P 〈0.05 vs sinus rhythm). In about two thirds of patients undergoing pacemaker implantation, recording of MAP-like electrograms was feasible with only minor modification of the atrial electrogram recording technique. The method should allow screening patients for electrophysiological alterations even before the onset of AF.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-1803
    Keywords: Key words Chronic heart failure – lung function – respiratory muscles – exercise – outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The extent and time-course of changes in lung volumes, ventilatory efficiency at rest and during exercise, and respiratory muscle function and their influence on exercise limitation in congestive heart failure (CHF) are unclear. It is unknown whether respiratory muscle function may predict changes in exercise limitation or may be impaired in patients with poor outcome. 145 male patients (54±1 years) suffering from CHF (NYHA class I–III, mean 2.3±0.1), with a LVEF of 23±1 %, and a mean peak O2 uptake (VO2peak) 15.0±:0.5 mL×min−1×kg−1, were studied. They were grouped in Weber functional classes A to D according to their VO2peak. Significant increases in ventilatory equivalents for O2 and CO2 (VE/VCO2peak) and in dead space ventilation at rest and during exercise were found with increasing exercise limitation. Moreover, there was a correlation of static and dynamic lung volumes (inspiratory vital capacity, IVC, r = 0.43, P 〈 0.01), as well as of maximal inspiratory pressure (MIP; r = 0.46, P 〈 0.01) with VO2peak. Patients who died (n = 26) or were heart transplanted (n = 20) during a follow-up (mean 800 ± 10 days) had a reduced MIP (6.4 ± 0.4 kPa) as compared with survivors (n = 82; 9.3±0.7 kPa, P 〈 0.01). In a subgroup of 33 patients re-evaluated after six months, individual changes in IVC and VE/VCO2peak, but not in MIP, correlated to changes in VO2peak (r = 0.69 and r = 0.72 respectively; P 〈 0.01). In CHF, exercise limitation is associated with reversible lung restriction and inefficient ventilation at rest and during exercise. Patientss with severe CHF have a significant reduction in MIP, a finding that is associated with poor outcome.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1435-1803
    Keywords: Key words Adenosine – adenyl cyclase – ischaemia – infarction – preconditioning – protein kinase C – rat – signal transduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Acute myocardial ischaemia leads to a transient sensitisation of adenylyl cyclase which may contribute to the occurrence of malignant arrhythmias and the propagation of myocardial necrosis. It is prevented by blockade of protein kinase C (PKC) which is activated in early ischaemia as shown by its translocation from the cytosol to the plasma membranes. Translocation of PKC may also occur in ischaemic preconditioning, a process thought to be induced by activation of adenosine A1 receptors. In this study it was investigated whether A1 adenosine receptors may be involved in the sensitisation of adenylyl cyclase and the activation of PKC induced by ischaemia. Methods:Isolated rat hearts were perfused with the specific A1 adenosine antagonist 8-caclopentyl-1,3-dipropylxanthine (DPCPX, 1 μM) or adenosine (1 μM) prior to ischaemia induced by stop of perfusion for 5 and 10 min. Adenylyl cyclase activity was determined in plasma membranes stimulated by forskolin or stimulated via β-receptors by isoproterenol. Total PKC activity was measured in purified plasma membranes and in the cytosolic fraction using histone III-S as a substrate. Results:Myocardial ischaemia induced a β-receptor-independent sensitisation of adenylyl cyclase (forskolin-stimulated activity 515 ± 55 vs. 384 ± 30 pmol/min/mg protein) which was completely blocked by pre-perfusion with DPCPX (385 ± 23 vs. 386 ± 24 pmol/min/mg protein). DPCPX alone did not alter the responsiveness of adenylyl cyclase to stimulation. The stimulated adenylyl cyclase activity was increased by 20% after pre-perfusion with adenosine, mimicking the ischaemia-induced sensitisation. The effect of adenosine was not augmented by additional ischaemia. PKC activity was translocated from the cytosol to the plasma membranes by acute ischaemia, indicating an activation of the enzyme. This effect was completely abolished by DPCPX. Conclusion: These data demonstrate that in the rat heart the sensitisation of adenylyl cyclase in acute myocardial ischaemia is dependent on activation of A1 adenosine receptors. It is suggested that the sensitisation of adenylyl cyclase by adenosine or ischaemia might be mediated by an activation of PKC.
    Type of Medium: Electronic Resource
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