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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 493-500 
    ISSN: 1432-1041
    Keywords: isoprenaline ; desipramine ; total body fractional extraction ; cardiac output ; plasma catecholamines ; neuronal uptake ; sympathetic tone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The total body clearance and fractional extraction of isoprenaline (ISO) have been determined, and the relation between these parameters and cardiac output established. Whether desipramine, an inhibitor of neuronal uptake, altered the plasma catecholamine response to ISO was also investigated. Seven healthy subjects were given i.v., infusions of ISO in two, consecutive 25-min periods, at constant dose rates of 31–43 and 80–124 pmol·kg−1·min−1, respectively. The total-body (ER), pulmonary (ERp) and forearm (ERf) fractional extractions and the total body clearance (CL) of ISO were obtained from measurements of cardiac output and the steady-state ISO concentration in mixed central venous, arterial and forearm venous plasma. ISO-induced increases in cardiac output resulted in increases in CL, decreases in ER and no consistent change in ERf. ERp did not differ from zero. ISO also produced a dose-dependent increase in the mixed venous plasma concentrations of noradrenaline and 3,4-dihydroxyphenylglycol (DOPEG), and a decrease in that of adrenaline. Pretreatment with desipramine did not alter any of the pharmacokinetic parameters of ISO. Desipramine, however, reduced the mixed venous baseline plasma levels of noradrenaline (47%) and DOPEG (40%), and tended to reduce that of adrenaline (34%). It enhanced the plasma noradrenaline response 2.4-fold, abolished the plasma DOPEG response and did not alter the plasma adrenaline response to ISO. Hence, owing to its haemodynamic effects, ISO modifies its own pharmacokinetics which involve non-neuronal removal processes only. The increased DOPEG in plasma resulting from the ISO-induced increase in noradrenaline release was presynaptic in origin. Desipramine appears to reduce sympathetic activity. The enhancement by desipramine of the ISO-induced increase in plasma noradrenaline points towards recapture by neuronal uptake of at least 58% of the noradrenaline released in response to ISO.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Numerical algorithms 19 (1998), S. 127-145 
    ISSN: 1572-9265
    Keywords: index ; DAE ; implicit equations ; solvability ; formal integrability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Mathematics
    Notes: Abstract It has been shown [17,18,21] that the notion of index for DAEs (Differential Algebraic Equations), or more generally implicit differential equations, could be interpreted in the framework of the formal theory of PDEs. Such an approach has at least two decisive advantages: on the one hand, its definition is not restricted to a “state-space” formulation (order one systems), so that it may be computed on “natural” model equations coming from physics (which can be, for example, second or fourth order in mechanics, second order in electricity, etc.) and there is no need to destroy this natural way through a first order rewriting. On the other hand, this formal framework allows for a straightforward generalization of the index to the case of PDEs (either “ordinary” or “algebraic”). In the present work, we analyze several notions of index that appeared in the literature and give a simple interpretation of each of them in the same general framework and exhibit the links they have with each other, from the formal point of view. Namely, we shall revisit the notions of differential, perturbation, local, global indices and try to give some clarification on the solvability of DAEs, with examples on time-varying implicit linear DAEs. No algorithmic results will be given here (see [34,35] for computational issues) but it has to be said that the complexity of computing the index, whatever approach is taken, is that of differential elimination, which makes it a difficult problem. We show that in fact one essential concept for our approach is that of formal integrability for usual DAEs and that of involution for PDEs. We concentrate here on the first, for the sake of simplicity. Last, because of the huge amount of work on DAEs in the past two decades, we shall mainly mention the most recent results.
    Type of Medium: Electronic Resource
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