Drug contact time dominates a necessary time for myocardial cells necrosis by a photodynamic reaction

We studied the necessary time for cell necrosis on myocardial cells against a photodynamic reaction using talaporfin sodium with various drug contact time in vitro. We have developed a new methodology of cardiac catheter ablation for tachyarrhythmia using a photodynamic reaction. To realize an immediate electrical conduction block within a few minutes, we intended to occur the photodynamic reaction outside the cells by using a short drug contact time. In a clinical situation, the drug distribution around the cells changes continuously after the drug administration. To study the change of electrical conduction block performance with these drug distribution change, we measured the necessary time for myocardial cell necrosis with various drug contact time. The concentration of intracellular Ca 2+ ion was measured by Fluo-4 AM fluorescence dye during the photodynamic reaction with excitation light of 663 nm in wavelength under a confocal microscope. The time for myocardial cell necrosis was evaluated using a decrease of Ca 2+ ion after the cell membrane rupture. The drug contact time for myocardial cells was varied 1-60 min. We obtained that the necessary time for myocardial cell decreased until around 10 min of drug contact time, and it increased after around 20 min of drug contact time. We suggest that the drug contact time within 10-20 min would the most effective timing to minimize the necessary time for myocardial cell necrosis using photodynamic reaction since the oxidative stress during uptake process would be high.