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

摘要

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