Myocardial electrical conduction block induced by photosensitization reaction in exposed porcine hearts in vivo

Ito, Arisa; Miyoshi, Shunichiro; Kimura, Tokuhiro; Takatsuki, Seiji; Fukumoto, Kotaro; Fukuda, Keiichi; Arai, Tsunenori

doi:10.1002/lsm.21136

Cited by 21 publications

(15 citation statements)

References 33 publications

(41 reference statements)

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“…In our previous report, a successful PDTmediated conduction block using a simple silica optical fiber with 208 J/cm 2 of irradiation induced a maximum temperature increase of 12.8°C measured by an infrared thermal camera. 12 Because infrared thermal cameras are subject to errors attributable to the use of red laser light, we used various temperature monitors in this study and developed a new PDT laser catheter, which also enabled us to monitor backscattering of the laser and avoid blood charring attributable to any sudden temperature increase. 16,17 The present study clearly demonstrated that lesion induction by PDT was not mediated by heat.…”

Section: Discussionmentioning

confidence: 99%

“…A custom-made 4-polar 7-French deflectable laser catheter was placed at the isthmus and manipulated as for the radiofrequency ablation procedure and reported in previous studies. 6 Because our previous study showed that a total of 300 J/cm 2 was required to obtain the acute conduction block in a porcine model, 12 we set the irradiance to 10 W/cm 2 and the duration of each irradiation to 30 seconds by a point-by-point fashion to prove the nature of nonthermal ablation. According to previous reports, intercaval and connected transverse lesions were required to ensure the establishment of a CTI conduction block in the canine atrial flutter ablation model.…”

Section: Ablation Proceduresmentioning

confidence: 99%

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Nonthermal Cardiac Catheter Ablation Using Photodynamic Therapy

Kimura

Takatsuki

Miyoshi

et al. 2013

Circ: Arrhythmia and Electrophysiology

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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.)

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Section: Discussionmentioning

confidence: 99%

Section: Ablation Proceduresmentioning

confidence: 99%

Nonthermal Cardiac Catheter Ablation Using Photodynamic Therapy

Kimura

Takatsuki

Miyoshi

et al. 2013

Circ: Arrhythmia and Electrophysiology

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“…In radio- frequency ablation therapy for tachyarrhythmia, severe thermal changes cause complications to arise [9,10]; therefore, ablation methods that minimize thermal damage to the myocardium should be developed. A new application of the photosensitization reaction for myocardium electrical conduction block to tachyarrhythmia has been proposed [11][12][13]. Ito et al used Talaporfin sodium and rat myocardial cells to investigate in vitro photosensitization reactions with short drug-light intervals.…”

Section: Introductionmentioning

confidence: 99%

Detailed in vitro study of the photosensitization reaction of extracellular talaporfin sodium in rat myocardial cells

2013

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This in vitro system for the extracellular photosensitization reaction may reflect the situation in live myocardial tissue. We found that the extracellular photosensitization reaction progressed in two distinctive phases; the first phase depended upon dissolved oxygen, and the second upon the molar density ratio between Talaporfin sodium and albumin. Cell lethality due to the extracellular photosensitization reaction was influenced by both of these factors in our in vitro system. We suggest that a photosensitizer concentration of 25 µg/ml might be necessary to treat myocardial tissue with therapies involving the extracellular photosensitization reaction.

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“…Severe thermal complications such as cardiac tamponade, pulmonary vein stenosis, cerebral infraction, phrenic nerve injury, and esophageal fistula are the problem [2]. We have proposed to apply the extracellular photosensitization reaction as a new non-thermal treatment methodology for tachyarrhythmia [3][4][5][6]. We intended to obtain the electrophysiological conduction block performance by oxidation of singlet oxygen produced by the extracellular photosensitization reaction with short drug-light interval.…”

Section: Introductionmentioning

confidence: 99%

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

Ogawa

Ito

Arai

2014

2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society

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We investigated the extracellular photosensitization effect on myocardial cells using talaporfin sodium at various irradiance measuring cell lethality dependence on talaporfin sodium concentration and immediate response of intracellular Ca(2+) as a fundamental study of the application for tachyarrhythmia treatment. The myocardial cell lethality was measured 2 h after the photosensitization reaction by WST assay varying the irradiance from 0.12 to 0.66 W/cm(2). The intracellular Ca(2+) of myocardial cell was observed during and until 10 min after the extracellular photosensitization reaction using fluo-4 AM and a confocal microscope varying the irradiance. The linear increasing behavior of the myocardial cell lethality with talaporfin sodium concentration was similarly obtained in the case of 0.12 and 0.29 W/cm(2) in irradiance. The photocytotoxicity was not obtained in the case of 0.46 and 0.66 W/cm(2) in irradiance. The time response of necrosis occurrence after the beginning of the extracellular photosensitization reaction was decreased with the irradiance increasing. We prospect that it may be caused by oxygen depletion in our in vitro system using 96 well plate since the irradiance and talaporfin sodium concentration were higher comparing the in vitro conditions of the general PDT for cancer.

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Myocardial electrical conduction block induced by photosensitization reaction in exposed porcine hearts in vivo

Abstract: The results suggest that the photosensitization reaction might induce acute and chronic myocardial electrical conduction block. Cardiac ablation with the photosensitization reaction might be a non-temperature-mediated methodology for arrhythmia therapy.

Cited by 21 publications

References 33 publications

Nonthermal Cardiac Catheter Ablation Using Photodynamic Therapy

Nonthermal Cardiac Catheter Ablation Using Photodynamic Therapy

Detailed in vitro study of the photosensitization reaction of extracellular talaporfin sodium in rat myocardial cells

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

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