Measurements of Electrophysiological Effects of Components of Acute Ischemia in Langendorff-Perfused Rat Hearts Using Voltage-Sensitive Dye Mapping

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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.

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