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 Ca2+ 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 Ca2+ 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.
We studied how the photosensitizer contact time affects the myocardial necrosis time during photodynamic therapy under a confocal microscopic system. Electrical conduction block by photodynamic reaction would be utilized as new catheter ablation for tachyarrhythmia to reduce complications. Photodynamic therapy with a short drug-light interval, which induces the oxidation mainly on the cell membrane is profitable to induce immediate myocardial cell necrosis. The necessary time to induce necrosis is important in the catheter ablation since the real-time electrocardiogram diagnosis is used to judge the treatment effect in clinical. The photosensitizer distribution changes from moment to moment during the therapy in vivo. It is necessary to investigate the time dependence of myocardial cell necrosis with various photosensitizer contact time in vitro. We measured the intracellular Ca2+ using fluo-4 AM during and after the photosensitization reaction. Talaporfin sodium was used as the photosensitizer, a CW red diode laser of 664 nm in wavelength was used for the photosensitizer excitation. Irradiance was 120 mW/cm2 . The necrosis occurrence time was analyzed as the sufficient intracellular Ca2+ decrease after the membrane rupture. The photosensitizer contact time was varied up to 60 min. The necessary time for the myocardial cell necrosis decreased with photosensitizer contact time increasing and the necessary time for the myocardial cell necrosis reached a minimum value of 150 s when photosensitizer contact time was 15 min. After 15 min of photosensitizer contact time, the necessary time for the myocardial cell necrosis increased as photosensitizer contact time increased.
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