Key result
In simulated ischemic conditions of hyperkalemia and acidosis, E-4031 and dofetilide demonstrated significantly reduced blockade of I(Kr) and total outward current, resulting in loss of class III effect.
Why the study?
Do E-4031 and dofetilide maintain their class III antiarrhythmic effects (I(Kr) blockade) during simulated ischemia (hyperkalemia and acidosis) in rabbit ventricular myocytes?
Population
Voltage-clamped single rabbit ventricular myocytes
Comparison
E-4031 and dofetilide in simulated ischemic… vs E-4031 and dofetilide in physiologic solution
Design
Preclinical
Authors
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May limit I(Kr) blocker utility in ischemia; hypothesis-generating and requires clinical translation studies.
Do E-4031 and dofetilide maintain their class III antiarrhythmic effects (I(Kr) blockade) during simulated ischemia (hyperkalemia and acidosis) in rabbit ventricular myocytes?
Simulated ischemic conditions (hyperkalemia and acidosis) reduce the I(Kr) blocking efficacy of E-4031 and dofetilide, suggesting a loss of their class III antiarrhythmic effect during ischemia.
West et al. (1997) studied Simulated ischemia (hyperkalemia and acidosis). E-4031 and dofetilide vs. Physiologic solution was evaluated on Blockade of I(Kr) and total outward current. In simulated ischemic conditions of hyperkalemia and acidosis, E-4031 and dofetilide demonstrated significantly reduced blockade of I(Kr) and total outward current, resulting in loss of class III effect.
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