PAF Antagonists as Potential Therapeutic Agents in Cardiac Anaphylaxis and Myocardial Ischemia

Koltai, M.; Tósaki, Árpád; Guillon, Jean‐Michel; Hosford, David; Braquet, P.

doi:10.1111/j.1527-3466.1989.tb00526.x

Cited by 21 publications

(13 citation statements)

References 57 publications

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“…Other experimental evidence implicates PAF alterations in cardiac function. PAF receptor antagonists are protective in models of myocardial ischemia (4,22,23). More focused experiments with paced isolated human atrial tissue and guinea pig papillary muscle suggest that PAF has a direct negative inotropic effect (12,13).…”

Section: Discussionmentioning

confidence: 99%

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Molecular and cellular actions of platelet-activating factor in rat heart cells.

Massey¹,

Kohout²,

Gaa³

et al. 1991

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 99%

“…This phospholipid is now known to have profound ef-fects on many tissues including muscle cells, vascular tissue, and neurons (3)(4)(5). PAF can be synthesized in and released from many tissues including kidney, lung, and heart, as well as from cells in the circulation in response to appropriate stimuli (3,(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Molecular and cellular actions of platelet-activating factor in rat heart cells.

Massey¹,

Kohout²,

Gaa³

et al. 1991

J. Clin. Invest.

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“…Such events are not surprising considering the nature of the patients in this study. Lexipafant has not been associated with cardiac arrhythmia in experimental animals or in clinical studies and, as mentioned below, some workers have reported PAF antagonists to be anti-arrhythmic in experimental myocardial ischaemia [14,20].…”

Section: Discussionmentioning

confidence: 96%

“…There is some evidence for the involvement of platelet-activating factor (PAF) in these phenomena. PAF is a potently active, smallmolecular-mass phospholipid that is generated from membrane phospholipids and contributes to pathophysiology in a wide variety of allergic, inflammatory and ischaemic responses [12][13][14]. The cardiovascular and other biological effects of PAF are many, including the induction of hypotension and platelet aggregation, which can be inhibited by PAF-receptor-specific antagonists [13,14].…”

Section: Introductionmentioning

confidence: 99%

Platelet-activating factor antagonism and streptokinase-induced hypotension in clinical acute myocardial infarction

Taylor¹,

Fatovich²,

HITCHCOCK³

et al. 2001

Clinical Science

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Continuing efforts are being made to improve thrombolytic therapy for acute myocardial infarction (AMI). The rate of streptokinase (SK) infusion is commonly limited by the hypotension that is induced. If this could be avoided, an accelerated regimen of SK could be given, analagous to that used for other thrombolytic agents such as alteplase. The mechanism of the SK-induced hypotension is unknown, but there is some evidence that platelet-activating factor (PAF) plays a role. The potent PAF receptor antagonist lexipafant (10 mg) (n=35), or matching placebo (n=36), was administered intravenously over 5 min, in a randomized double-blinded protocol, to consecutive patients about to receive SK for AMI; all but three had inferior MI, because of the preference for strategies other than SK therapy in patients with anterior MI. The rate of infusion of SK was set to give 1.5x10(6) units over 30 min, anticipating significant hypotension. Blood pressure fell sharply over the first 10 min of SK administration. The maximum fall in systolic blood pressure occurred between 8 and 12 min, and averaged 43+/-28 mmHg (mean+/-S.D.) and 40+/-26 mmHg in patients given placebo and lexipafant respectively. Systolic pressure having fallen to <90 mmHg, according to protocol the SK administration rate was reduced in 21 of 36 (58%) of patients given placebo and in 19 of 35 (54%) of patients given lexipafant. The total SK dose was given to all subjects over 40.3+/-17.5 and 40.2+/-13.4 min for the placebo and lexipafant groups respectively. Peak and time integrals of creatine kinase were not different in the two groups. There were no adverse effects attributable to lexipafant. It is concluded that the PAF receptor antagonist lexipafant has no significant effect on SK-induced hypotension and does not facilitate an accelerated regimen of administration.

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“…EGb 761 improves global and local cerebral blood flow, microcirculation, blood rheology, and tissue metabolism, protects against hypoxia, and reduces capillary permeability [see DeFeudis, 19911, and some reports indicate that it also affects cardiac function [e.g., Koltai et al, 1989;Wainwright and Parratt, 1989;Pietri et al, 1993;Culcasi et al, 1993;Tosaki and Droy-Lefaix, 19931.…”

Section: Introductionmentioning

confidence: 98%

Effects of an extract of Ginkgo biloba On the action potential and associated transmembrane ionic currents in mammalian cardiac myocytes: Inhibition of isoproterenol‐induced chloride current

Masson¹,

Néliat²,

Drieu

et al. 1994

Drug Development Research

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Ventricular myocytes of guinea pig heart were used to examine the effects of an extract of Ginkgo biloba (EGb 761) on the action potential and individual transmembrane ionic currents. Electrophysiological events were recorded using the "whole-cell" configuration of the patch-clamp technique. A systematic analysis of the data revealed that EGb 761 (5-50 pg/ml) did not affect the normal action potential or the various ionic currents involved in its generation; i.e., fast inward sodium current (INa), inward calcium currents (ICaT and ICaL), delayed outward potassium current (IK), inward rectifying potassium current (IK,), and ATP-sensitive potassium current ( I, -, , , ) evoked by 2,4-dinitrophenol (2,4-DNP). However, EGb 761 (25 pg/ml) elicited a pronounced concentration-dependent and reversible inhibition of isoproterenol-induced CI-current (Icl), the maximal effect being observed at 50 pg/ml. This current may be significantly involved in sympathetic hyperactivity, hypoxia, and ischemia, pathophysiological conditions for which EGb 761 offers therapeutic benefit. The basic mechanism(s) underlying the inhibitory effect of EGb 761 on Ic1 and the constituent(s) of EGb 761 responsible for this action remain to be identified, but it seems clear, from results which showed that neither ginkgolide B (50-500 ngfml) nor bilobalide (150-1,500 ngiml) influenced this current, that a terpenoid constituent of EGb 761 is probably not involved. 0 1994 Wiley-Liss, Inc.

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PAF Antagonists as Potential Therapeutic Agents in Cardiac Anaphylaxis and Myocardial Ischemia

Cited by 21 publications

References 57 publications

Molecular and cellular actions of platelet-activating factor in rat heart cells.

Molecular and cellular actions of platelet-activating factor in rat heart cells.

Platelet-activating factor antagonism and streptokinase-induced hypotension in clinical acute myocardial infarction

Effects of an extract of Ginkgo biloba On the action potential and associated transmembrane ionic currents in mammalian cardiac myocytes: Inhibition of isoproterenol‐induced chloride current

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