Induction of delayed afterdepolarizations and triggered activity in canine Purkinje fibers by lysophosphoglycerides

Academic Article

Abstract

  • Lysophosphoglycerides accumulate in ischemic myocardium and induce electrophysiologic alterations in normoxic tissue in vitro closely resembling those seen with ischemia in vivo. Delayed afterdepolarizations and triggered activity may be particularly important in the pathogenesis of arrhythmias in the ischemic heart. The present study was performed to determine whether lysophosphatidylcholine (LPC), at concentrations comparable to those present in ischemic myocardium, can induce delayed afterdepolarizations and/or triggered activity in normoxic canine Purkinje fibers. In the present study, as little as 75 μM LPC was found to induce delayed afterdepolarizations and as little as 100 μM LPC was found to induce delayed afterdepolarizations and triggered activity even at low cycle lengths. The amplitude of the induced delayed afterdepolarizations was enhanced by augmentation of the extracellular concentration of calcium (7 mM) or by exogenous epinephrine (10-9 to 10-6 M). The amplitude was decreased by verapamil (1 mg/l) or Mn++ (2.5 mM). Epinephrine at a concentration of 10-6 M also initiated triggered activity in Purkinje fibers exposed to LPC (75 μM), a response blocked by l-propranolol (2 x 10-7 M and 10-6 M) but not by the α1-adrenergic blocking agent BE-2254 (10-6 M). Delayed arfterdepolarizations induced by LPC (75 μM) and epinephrine (10-6 M) persisted even in the presence of acidosis (pH 6.7) and hyperkalemia ([K+]0 = 7 mM). Thus, delayed afterdepolarizations and triggered activity induced by LPC may contribute to the induction and/or maintenance of arrhythmias early after the onset of myocardial ischemia. However, because of the reversal of these effects after superfusion with media devoid of LPC, they may occur with ischemia in vivo but not be seen in tissue isolated from ischemic regions and evaluated in vitro.
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    Author List

  • Pogwizd SM; Onufer JR; Kramer JB; Sobel BE; Corr PB
  • Start Page

  • 416
  • End Page

  • 426
  • Volume

  • 59
  • Issue

  • 4