Measurements of electrophysiological effects of components of acute ischemia in Langendorff-perfused rat hearts using voltage-sensitive dye mapping

Anders Nygren, István Baczkó, Wayne R. Giles

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Abstract

Introduction: This study was carried out to evaluate optical mapping in the presence of cytochalasin-D as a method for measuring electrophysiological responses in general, and in particular the responses to acute ischemia in the Langendorff-perfused rat heart. Cytochalasin-D is commonly used to reduce contraction for the purpose of suppressing motion artifacts in voltage-sensitive dye recordings of cardiac membrane potential. Methods and Results: Observations using optical mapping were complemented by recordings of the surface electrogram to provide information independent of the optical measurements. Perfusion of Langendorff-perfused rat hearts with 3 μM cytochalasin-D resulted in a 24% prolongation of the QT interval of surface electrograms indicating that cytochalasin-D prolongs the rat ventricular action potential. Individual components of the electrophysiological response to acute ischemia were globally induced as follows: (1) opening of KATP channels was induced by perfusion of 2 μM P-1075, (2) accumulation of extracellular K+ was simulated by increasing perfusate [K+] to 12 mM, and (3) acidosis was simulated by reducing perfusate pH to 6.5. The responses to these interventions could be reliably documented using optical recordings, as well as from surface electrograms. Whole-cell patch clamp measurements on isolated rat ventricular myocytes indicate that cytochalasin-D produces an approximately 2.5-fold increase in P-1075-induced IK,ATP. Conclusion: These results provide the necessary background information for interpreting electrophysiological measurements during acute ischemia in the presence of cytochalasin-D.

Original languageEnglish
Pages (from-to)S113-S123
JournalJournal of Cardiovascular Electrophysiology
Volume17
Issue numberSUPPL. 1
DOIs
Publication statusPublished - May 1 2006

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Keywords

  • Cytochalasin-D
  • Fluorescent dye imaging
  • Ischemia
  • Optical mapping

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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