Effects of a lipoxygenase inhibitor on digoxin-induced cardiac arrhythmias in the isolated perfused guinea-pig heart

Gök, Şule; Ülker, Sibel; Hüseyinov, Afig; Evinç, Akgün

doi:10.1016/s0306-3623(97)00018-9

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…In this study, it is unknown whether the enhanced production of leukotrienes in the cardiac tissues mediates digoxin-induced tachyarrhythmias. It has recently been shown in our previous study that BW A4C, a 5-lipoxygenase inhibitor, did not prevent the genesis of VT and VF inspite of the fact that it suppressed the digoxin-induced elevation LTB 4 levels in the coronary effluent [8]. Therefore, we postulated that excess LTB 4 synthesis could not be involved in the digoxin-induced arrhythmias and the impairment of cardiac functions; whereas pretreatment with a dual inhibitor of cyclooxygenase and lipoxygenase, BW 755C (5 and 10 mgWkg -1 i.v.…”

Section: Discussionmentioning

confidence: 75%

“…Treatment with leukotriene receptor antagonists and dual inhibitors (lipoxygenase and cyclooxygenase inhibitors) of arachidonic acid has been shown to attenuate the occurrence of digoxin-induced arrhythmias and prevent digoxin-induced ventricular fibrillation (VF) with a significant delay in mortality in anesthetized guinea pigs [6,7]. However, in a previous study done by us in a guinea-pig isolated heart preparation, it was reported that the lipoxygenase inhibitor, BW A4C, lacked any protective action on digoxin-induced arrhythmias, although it effectively inhibited the digoxininduced increase in LTB 4 in the coronary effluent [8].…”

Section: Introductionmentioning

confidence: 99%

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Possible Contribution of Leukotrienes in the Arrhythmogenic Effects of Digoxin on Isolated Guinea-Pig Hearts

1998

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The effect of a leukotriene D₄ (LTD₄) receptor antagonist, L-648,051, was investigated in digoxin-induced cardiac toxicity in isolated guinea-pig hearts (Langendorff preparation). Digoxin infusion (25 µg·ml^–1, 0.5 ml·min^–1) increased perfusion pressure and contractile force initially, but decreased them later. The onset of first ventricular premature beats (VPBs) matched the increase phase, but the decrease phase was accompanied by ventricular tachycardia (VT) and fibrillation (VF). In the presence of L-648,051 (5 µmol·l^–1), the initial phase was similar to that observed with digoxin alone, but the marked reduction was inhibited. This drug increased the concentration of digoxin required for VBSs and cardiac arrest, but it could not prevent the formation of VT and VF. The duration of VT was significantly decreased by L-648,051. It is concluded that the leukotriene receptor antagonist might have beneficial effects on digoxin-induced arrhythmias. Whether this effect depends on direct or indirect actions is uncertain.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Possible Contribution of Leukotrienes in the Arrhythmogenic Effects of Digoxin on Isolated Guinea-Pig Hearts

1998

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Contribution of Eicosanoids in the Heart

Malik¹

1999

Hormones and the Heart in Health and Disease

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Cardiotoxicity of digitalis glycosides: roles of autonomic pathways, autacoids and ion channels

Demiryürek

2005

Auton Autocoid Pharmacol

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1 Cardiac glycosides have been used for centuries as therapeutic agents for the treatment of heart diseases. In patients with heart failure, digoxin and the other glycosides exert their positive inotropic effect by inhibiting Na(+)-K(+)-ATPase, thereby increasing intracellular sodium, which, in turn, inhibits the Na(+)/Ca(2+) exchanger and increases intracellular calcium levels. As the therapeutic index of digitalis is narrow, arrhythmias are common problems in clinical practice. The mechanisms and mediators of these arrhythmias, however, are not completely understood. 2 The involvement of the sympathetic and parasympathetic nervous system in digitalis cardiac toxicity is reviewed. 3 Receptors, channels, exchange systems or other cellular components involved in digitalis-induced cardiotoxicity are also reviewed. 4 Possible mediators of digitalis-induced cardiac toxicity are discussed. 5 Management of digitalis toxicity in patients is summarized. 6 The determination of the possible mediators of digitalis-induced cardiac toxicity will enhance our knowledge and lead to the development of new therapeutic strategies to treat these lethal arrhythmias.

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Effects of a lipoxygenase inhibitor on digoxin-induced cardiac arrhythmias in the isolated perfused guinea-pig heart

Cited by 3 publications

References 13 publications

Possible Contribution of Leukotrienes in the Arrhythmogenic Effects of Digoxin on Isolated Guinea-Pig Hearts

Possible Contribution of Leukotrienes in the Arrhythmogenic Effects of Digoxin on Isolated Guinea-Pig Hearts

Contribution of Eicosanoids in the Heart

Cardiotoxicity of digitalis glycosides: roles of autonomic pathways, autacoids and ion channels

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