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, cul tured, spontaneously beating, neonatal rat cardiac myocytes were used to examine the effects of various eicosanoids added to the medium supe rfusing the cells at different concentrations on the contraction of th e 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 beat ing rate, chaotic activity and contractures. These effects are concent ration-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 cell s with a slight increase in the amplitude of the contractions and show ed 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 a mplitude of the contractions and effectively terminated the tachyarrhy thmias induced by arrhythmogemic agents, such as isoproterenol, ouabai n and U 46619. At higher concentrations (>5 mu M), PGE, caused cell co ntractures and chaotic activity In contrast, the lipoxygenase products [leukotriene (LT) B-4, LTC4, LTD4 & LTE4] of arachidonic acid (AA) ha d no significant effect on the myocyte contractions.