The new application of photosensitization reaction to atrial fibrillation treatment: mechanism and demonstration of non-thermal electrical conduction block with porcine heart

We have proposed non-thermal electrical conduction block for atrial fibrillation treatment by the photosensitization reaction, in which the interval time between the photosensitizer injection and irradiation is less than tenth of that in conventional way. To study the mechanism of photosensitization reaction-induced electrical conduction block, intracellular Ca2+ concentration change in rat myocardial cells was measured by fluorescent Ca2+ indicator Fluo-4 AM with confocal laser microscopy. Measured rapid increase in the fluorescence intensity and a change in cell morphology indicated that cell membrane damage; that is Ca2+ influx and eventually cell death caused by the photosensitization reaction. To demonstrate myocardial electrical conduction block induced by the photosensitization reaction, surgically exposed porcine heart under deep anesthesia was used. The myocardial tissue was paced with a stimulation electrode. The propagated electrical signals were measured by bipolar electrodes at two different positions. Thirty minutes after the injection of 5-10 mg/kg Porfimer sodium or Talaporfin sodium, the red laser light was irradiated to the tissue point by point crossing the measuring positions by the total energy density of less than 200 J/cm2. The electrical signal conduction between the measuring electrodes in the myocardial tissue was delayed by each irradiation procedure. The electrical conduction delay corresponded to the block line length was obtained. These results demonstrated the possibility of non-thermal electrical conduction block for atrial fibrillation treatment by the photosensitization reaction.

[1]  瀬口 秀孝 Propagation of Ca[2+] release in cardiac myocytes : role of mitochondria , 2007 .

[2]  S. F. Mironov,et al.  Visualizing excitation waves inside cardiac muscle using transillumination. , 2001, Biophysical journal.

[3]  Chih-Ching Wu,et al.  Subcellular localization of Photofrin® determines the death phenotype of human epidermoid carcinoma A431 cells triggered by photodynamic therapy: When plasma membranes are the main targets , 2003, Journal of cellular physiology.

[4]  F. Morady,et al.  Segmental Ostial Ablation to Isolate the Pulmonary Veins During Atrial Fibrillation: Feasibility and Mechanistic Insights , 2002, Circulation.

[5]  John B. Shoven,et al.  I , Edinburgh Medical and Surgical Journal.

[6]  Douglas Packer,et al.  Worldwide Survey on the Methods, Efficacy, and Safety of Catheter Ablation for Human Atrial Fibrillation , 2005, Circulation.

[7]  J Clémenty,et al.  Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. , 1998, The New England journal of medicine.

[8]  J Clémenty,et al.  Electrophysiological end point for catheter ablation of atrial fibrillation initiated from multiple pulmonary venous foci. , 2000, Circulation.

[9]  O. Alfieri,et al.  Atrial Electroanatomic Remodeling After Circumferential Radiofrequency Pulmonary Vein Ablation: Efficacy of an Anatomic Approach in a Large Cohort of Patients With Atrial Fibrillation , 2001, Circulation.

[10]  C. Tai,et al.  Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses, and effects of radiofrequency ablation. , 1999, Circulation.

[11]  O. Alfieri,et al.  Atrio-Esophageal Fistula as a Complication of Percutaneous Transcatheter Ablation of Atrial Fibrillation , 2004, Circulation.

[12]  Hiroki Matsuo,et al.  The mechanism of PDT-induced electrical blockade: the dependence of time-lapse localization of talaporfin sodium on the cell death phenotypes in rat cardiac myocytes , 2009, BiOS.

[13]  B. Wilson,et al.  IN VIVO and POST MORTEM MEASUREMENTS OF THE ATTENUATION SPECTRA OF LIGHT IN MAMMALIAN TISSUES , 1985, Photochemistry and photobiology.

[14]  D. Shah,et al.  Catheter Ablation of Chronic Atrial Fibrillation Targeting the Reinitiating Triggers , 2000, Journal of cardiovascular electrophysiology.

[15]  M W Berns,et al.  In vivo studies on the utilization of mono-L-aspartyl chlorin (NPe6) for photodynamic therapy. , 1987, Cancer research.

[16]  Paul M. Ripley,et al.  Photodynamic therapy for cancer of the pancreas , 2002, Gut.

[17]  F. Morady,et al.  Risk of Thromboembolic Events After Percutaneous Left Atrial Radiofrequency Ablation of Atrial Fibrillation , 2006, Circulation.

[18]  M W Berns,et al.  In vitro characterization of monoaspartyl chlorin e6 and diaspartyl chlorin e6 for photodynamic therapy. , 1988, Journal of the National Cancer Institute.

[19]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[20]  Stephen S. Cha,et al.  Secular Trends in Incidence of Atrial Fibrillation in Olmsted County, Minnesota, 1980 to 2000, and Implications on the Projections for Future Prevalence , 2006, Circulation.