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  • Title: Effects of platelet-activating factor on beta- and H2-receptor-mediated increase of myocardial contractile force in isolated perfused guinea pig hearts.
    Author: Felix SB, Baumann G, Niemczyk M, Ahmad Z, Hashemi T, Berdel WE.
    Journal: Res Exp Med (Berl); 1991; 191(1):1-9. PubMed ID: 1852056.
    Abstract:
    Platelet-activating factor (PAF) has been termed an important mediator of cardiovascular shock due to immunological reactions, including anaphylaxis and endotoxic reactions. Previous studies have shown that PAF is a potent cardiodepressive agent inducing a drastic coronary constriction and a sustained impairment of myocardial contractility. In this study, an attempt was made to further characterize the prolonged PAF effects on coronary circulation and myocardial contractile force in the isolated guinea pig heart perfused at constant pressure. An intracoronary PAF bolus (0.18 nmol, related to coronary flow rates of 1 ml/min) induced a precipitous decrease of coronary flow rates, left ventricular pressure, and left ventricular contraction (peak positive dP/dt), which was followed by a slow increase reaching new steady state after 15 min (-48%, -40%, -42% below baseline, respectively). If the specific PAF antagonist WEB 2086 (3.65 nmol/min, related to coronary flow rates of 1 ml/min) was infused 30 min after PAF administration, the prolonged PAF-mediated cardio-depressive effects were rapidly reversed. Several studies indicate that PAF induces a down regulation of beta-adrenoreceptors in different cell types, including human lung tissue. Therefore, a further objective of the study was to evaluate whether PAF selectively impairs the positive inotropic effects of beta-receptor agonists or also inhibits the contractile effects of inotropic drugs, which are known to enhance cardiac contractility independently of beta-receptors. In these experiments, the beta-agonist isoproterenol and the H2-agonist impromidine were administered as intracoronary boluses (0.35 nmol and 0.14 nmol, respectively, related to coronary flow rates of 1 ml/min) prior to PAF injection and 30 min after PAF.(ABSTRACT TRUNCATED AT 250 WORDS)
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