The ionic mechanism of reperfusion-induced early afterdepolarizations in feline left ventricular hypertrophy

Tetsushi Furukawa, Arthur L. Bassett, Nanako Furukawa, Shinichi Kimura, Robert J. Myerburg

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Left ventricular hypertrophy (LVH) potentiates reperfusion-associated ventricular fibrillation. To study the mechanism responsible, patch-clamp techniques were used to evaluate transmembrane ionic currents during "reperfusion" after a CN- -induced metabolic surrogate for ischemia in isolated myocytes from a feline model of experimental LVH. Reperfusion caused the generation of early afterdepolarizations (EADs) from an average take-off potential of -33 mV in LVH cells but not in cells from normal hearts. 10 min after initiating reperfusion of normal cells, action potential duration (APD) at 50% repolarization (APD50) lengthened from 198±41 to 233±57 ms whereas in LVH cells APD50 lengthened from 262±84 to 349±131 ms (P < 0.05). Among the LVH ceils, APD50 lengthening was significantly greater in the cells that had developed EADs. During reperfusion, steady state outward current in the voltage range of the action potential plateau (between -20 and +20 mV) was reduced from the control values in LVH cells but not in normal cells. Reperfusion-related reduction of steady state outward current in LVH cells was abolished under experimental conditions in which L-type Ca2+ current was isolated from other classes of currents whereas it was still observed under the condition in which pure K+ currents could be recorded. Thus, reduction of steady state outward current due to the reduction of outward K+ current over the action potential plateau voltage range appears to be responsible for an excessive prolongation of APD, leading to the development of EADs.

Original languageEnglish (US)
Pages (from-to)1521-1531
Number of pages11
JournalJournal of Clinical Investigation
Volume91
Issue number4
DOIs
StatePublished - Apr 1993

Keywords

  • Aortic constriction
  • Calcium current
  • Early afterdepolarization
  • Potassium current
  • Pressure overload
  • Reperfusion

ASJC Scopus subject areas

  • Medicine(all)

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