The Myocardial Electrical Blockade Induced by Photosensitization Reaction

The authors studied the application of photosensitization-reaction-induced cytotoxicity to establish electrical blockade of myocardial tissue. This photosensitization-reaction-induced cytotoxicity, i.e., photodynamic therapy (PDT) was performed with chlorine photosensitizer, talaporfin sodium, and a red (670 nm) diode laser. The cytotoxicity on rat cardiac myocytes and the electrical blockade by PDT using rat myocardial tissue were confirmed. The mechanism of PDT-induced electrical blockade was investigated. The photosensitization-reaction-induced cytotoxicity in normal rat cardiac myocytes was obtained in cell lethality measurement. The ex vivo experiment with rat-isolated myocardial tissue demonstrated the immediate electrical blockade by PDT. Moreover, the possibility of permanent electrical blockade by PDT using rat atrioventricular blockade model was confirmed. To study the mechanism of the acute electrical blockade obtained in the ex vivo study, intracellular Ca²⁺ concentration changes in rat cardiac myocytes were measured by the intensity of the fluorescent Ca²⁺ indicator Fluo-4 AM. A rapid increase in fluorescence intensity during the photosensitization reaction and a change in cell morphology after the photosensitization reaction were observed. These results indicate that cell membrane damage, Ca²⁺ influx, and eventually cell death are caused by the photosensitization reaction. The necrosis-like cell death induced by the photosensitization reaction can explain a permanent electrical blockade of the myocardial tissue in vivo by PDT.