Differential effects of various eicosanoids on the production or prevention of arrhythmias in cultured neonatal rat cardiac myocytes

To identify the arrhythmogenic and the antiarrhythmic eicosanoids, cultured, spontaneously beating, neonatal rat cardiac myocytes were used to examine the effects of various eicosanoids added to the medium superfusing the cells at different concentrations on the contraction of the myocytes. Superfusion of the myocytes with the prostaglandins (PGD(2), PGE(2), PGF(2 alpha)) or the thromboxane (TXA(2))-mimetic, U 46619, induced reversible tacharrhythmias characterized by an increased beating rate, chaotic activity and contractures. These effects are concentration-dependent. PGF(2 alpha) and U 46619 were much more potent than PGD(2) or PGE(2) in the production of tachyarrhythmias. Prostacyclin (PGI(2)) induced a marked reduction in the contraction rate of the cells with a slight increase in the amplitude of the contractions and showed a protective effect against the arrhythmias induced by PGF(2 alpha) and TXA(2) (U 46619). PGE(1) exerted a dose-dependent dual effect on the contraction of the myocytes. At low concentrations (<2 mu M), PGE(1) reduced the contraction rate of the cells with an increase in the amplitude of the contractions and effectively terminated the tachyarrhythmias induced by arrhythmogemic agents, such as isoproterenol, ouabain and U 46619. At higher concentrations (>5 mu M), PGE, caused cell contractures and chaotic activity In contrast, the lipoxygenase products [leukotriene (LT) B-4, LTC4, LTD4 & LTE4] of arachidonic acid (AA) had no significant effect on the myocyte contractions.