Nonthermal Cardiac Catheter Ablation Using Photodynamic Therapy

Abstract

Background-Radiofrequency ablation has limitations, largely related to creation of lesions by heating. Here, we report the first nonthermal ablation by applying photodynamic therapy (PDT) to cardiac tissues using a custom-made deflectable laser catheter. The present study investigated the feasibility of PDT for cavotricuspid isthmus ablation in a canine model. Methods and Results-We evaluated the pharmacokinetic profiles of 17 canines after administration of a photosensitizer (talaporfin sodium) by various protocols. We succeeded in maintaining the photosensitizer concentration at a level in excess of the clinically effective dose for humans. Using a 4-polar 7-French deflectable laser catheter, we performed PDT-mediated cavotricuspid isthmus ablation in 8 canines. PDT caused oxidative injury only to the irradiated area and successfully produced a persistent electric conduction block. No acute, gross changes such as edematous degeneration, thrombus formation, steam pops, or traumatic injury were observed after irradiation. Hematoxylin and eosin staining of tissues samples also showed well-preserved endothelial layers. Testing of the blood samples taken before and after the procedure revealed no remarkable changes. Lesion size at 2 weeks after the procedure and the temperature data collected during irradiation were compared between the PDT and irrigated radiofrequency ablation procedures. A ventricular crosssection revealed a solid PDT lesion, which was as deep as a radiofrequency lesion. In addition, endocardial, surficial, and intramural temperature monitoring during the PDT irradiation clearly demonstrated the nonthermal nature of the ablation technique. Conclusions-Nonthermal PDT-mediated catheter ablation is a potentially novel treatment for cardiac arrhythmias.(Circ Arrhythm Electrophysiol. 2013;6:1025-1031.)

Evaluation of human and bovine serum albumin on oxidation characteristics by a photosensitization reaction under complete binding of talaporfin sodium

“…However we think that you should use human serum albumin as a binding protein for talaporfin sodium in the fundamental study of clinical application with the photosensitization reaction in vitro, in particular, photodynamic antimicrobial chemotherapy [3] and our proposed arrhythmia ablation [4] using extra-cellular photosensitization reaction. …”

“…The photosensitizer accumulation to malignant tumors is induced by activation of low-density lipoprotein receptors and low excretion by immature lymph vessels [2]. On the other hands, photodynamic antimicrobial chemotherapy and our proposed arrhythmia therapy by cardiomyocyte oxidation have been used with an extra-cellular photosensitization reaction, because photosensitizer doesn't accumulate in healthy tissues [3,4]. Despite the photosensitization reaction generally being evaluated with various cells and tissues, we have used a simple experimental set-up with a solution including the photosensitizer and binding proteins to study the therapeutic interaction.…”

“…Despite the photosensitization reaction generally being evaluated with various cells and tissues, we have used a simple experimental set-up with a solution including the photosensitizer and binding proteins to study the therapeutic interaction. We have used talaporfin sodium, a second-generation chlorine photosensitizer, in this reaction for arrhythmia therapy [4]. Notably, 70% of talaporfin sodium binds with albumin in the interstitial spaces of living human tissues [5], which is where the reaction for our arrhythmia therapy takes place.…”

Immediate response and cytotoxicity effect on myocardial cells by extracellular photosensitization reaction varying irradiance

“…necrosis in the extracellular photosensitization reaction [3]. We have reported the cell killing effect by extracellular photosensitization reaction with various talaporfin sodium concentrations and radiant exposures [7]. The myocardial cell interaction with various irradiances is needed to understand the electrical conduction block myocardium that has certain depth since the irradiance decreased with the depth in myocardium by absorption and scattering.…”

Immediate response of Ca2+concentration in myocardial cells against oxidation stress by extracellular photosensitization reaction using Talaporfin sodium for the arrhythmia treatment application

“…Some severe complications such as cardiac tamponade, pulmonary vein stenosis, cerebral infraction, phrenic nerve injury, and esophageal fistula caused by heat generation are the problem of the radio-frequency catheter ablation [2][3]. So that we have proposed to apply extracellular photosensitization reaction for a new non-thermal treatment of tachyarrhythmia to solve the complications caused by heat [4][5][6][7]. We have studied the photocytotoxicity effect on myocardial cells by extracellular photosensitization reaction measuring cell lethality using in vitro experimental system.…”