We studied time response of electrical conduction (EC) block in a novel cardiomyocyte wire by extra-cellular
photosensitization reaction (EPR) at various irradiances. This EC block using the EPR has been studied to develop a
non-thermal arrhythmia therapeutic methodology. Despite the EC block in acute phase is needed to judge therapeutic
endpoint in clinical arrhythmia therapy, time response of the EC block by the EPR in acute phase hasn’t been studied.
We measured the time to EC block occurrence by the EPR with intra-cellular Ca2+ concentration change using Fluo-4
AM fluorescence measurement by a confocal laser microscope system. The pattern cultivation cover glass with 10 mm
Φ which had 60 μm width cultivation areas with 300 μm separations was used to form the cardiomyocyte wires. Rat
cardiomyocyte with 10.8×105 cells was disseminated to the cover glasses installed in a 35 mmΦ dish. After 3 days from
the dissemination, the EPR was operated to the cardiomyocyte wires for 10 min varying 3-120 mW/cm2 in 663 nm laser
irradiances with 20 μg/ml talaporfin sodium. An irradiation area was approximately 60×340 μm2 on each wires. Cross
correlation functions (CCF) in measured fluorescence images in every 10 s were calculated across the irradiation area.
The time to EC block occurrence was defined as the time of the max difference between adjacent CCFs. By decreasing
irradiances in 30-6 mW/cm2, the time to EC block occurrence became longer from 294 to 434 s. In 30-120 mW/cm2, the
time to EC block occurrence was nearly constant in 300 s.
We experimentally studied the correlation between myocardial damage depth due to the extracellular photosensitization
reaction (PR) using talaporfin sodium and fluorescence-fall amount (FA), which is calculated from the measured
backscattering fluorescence intensity via a manipulatable 7 Fr. laser catheter during the PR operation in vivo to establish
treatment depth predictor for a non-thermal tachyarrhythmia treatment. The PR was performed to left and/or right
ventricle in the open-chest canine heart. The laser irradiation of 663±2 nm in wavelength via the laser catheter was
operated 15 min after the intravenous administration of talaporfin sodium with concentration of 36.2±8.0 μg/ml in plasma. The irradiation was operated with irradiance of 5, 10, 20 W/cm2, and duration of 5, 10, 20 s. Backscattering
fluorescence of 710±2 nm in wavelength was measured via the laser catheter during the PR. The FA was calculated
multiplying the irradiation duration by the fluorescence-fall, which is subtraction of the fluorescence intensity at the
kickoff and end of the irradiation. The canine heart was extracted 1 week after the PR and HE stained specimen was
histologically evaluated. The correlation of the myocardial damage depth and FA was investigated. We found that FA
obtained a logarithmic relation to the myocardial damage depth. We think that the FA might be available to predict the
PR induced myocardial damage depth for the application of tachyarrhythmia treatment under catheterization in vivo.
In order to understand extracellular-photosensitization reaction (PR) using talaporfin sodium, we studied comparison of oxidation dynamics of albumin and talaporfin sodium in solution system by visible and ultraviolet absorption spectrum measurements. Almost all talaporfin sodium particles may be bound to albumin in interstitial fluid, and this binding would affect the oxidation dynamics during this PR. Bovine serum albumin (BSA) is commonly used in vitro study but its binding characteristics with talaporfin sodium are different from human serum albumin (HSA). PR was operated in a solution composed of 20 μg/ml talaporfin sodium and 1.3 mg/ml HSA or BSA to simulate myocardial extracellular PR condition. Laser radiation of 662 nm was irradiated to this solution with irradiance of 0.29 W/cm2. Absorption spectra of these solutions were measured during the PR. We estimated oxidized ratio by absorption difference around 240 nm before and after the PR. Talaporfin sodium was oxidized 100% with HSA and BSA by the PR of 100 J/cm2 in radiant exposure. On the other hand, HSA and BSA were oxidized 60% and 94%, respectively in this radiant exposure. Q-band absorption peak of talaporfin sodium with HSA was shifted to 1 nm longer wavelength increasing radiant exposure up to 100 J/cm2. This longer wavelength shift would mean binding ratio of non-oxidized talaporfin sodium to non-oxidized HSA was increased with increasing radiant exposure. Therefore it would be possible that PR with talaporfin sodium bound to HSA might present efficient PDT than PR bound to BSA.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.