Natsumi Shimazaki

Keio University, Edo, Tōkyō, Japan

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Publications (15)0 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We studied the relations between the time history of smooth muscle cells (SMCs) death rate and heating condition in vitro to clarify cell death mechanism in heating angioplasty, in particular under the condition in which intimal hyperplasia growth had been prevented in vivo swine experiment. A flow heating system on the microscope stage was used for the SMCs death rate measurement during or after the heating. The cells were loaded step-heating by heated flow using a heater equipped in a Photo-thermo dynamic balloon. The heating temperature was set to 37, 50-60°C. The SMCs death rate was calculated by a division of PI stained cell number by Hoechst33342 stained cell number. The SMCs death rate increased 5-10% linearly during 20 s with the heating. The SMCs death rate increased with duration up to 15 min after 5 s heating. Because fragmented nuclei were observed from approximately 5 min after the heating, we defined that acute necrosis and late necrosis were corresponded to within 5 min after the heating and over 5 min after the heating, respectively. This late necrosis is probably corresponding to apoptosis. The ratio of necrotic interaction divided the acute necrosis rate by the late necrosis was calculated based on this consideration as 1.3 under the particular condition in which intimal hyperplasia growth was prevented in vivo previous porcine experiment. We think that necrotic interaction rate is larger than expected rate to obtain intimal hyperplasia suppression.
    01/2014;
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    ABSTRACT: We proposed a short-duration heating balloon angioplasty. We designed a prototype short-duration heating balloon catheter that can heat artery media to 60-70°C within 15-25 s with a combination of laser-driven heat generation and continuous fluid irrigation in the balloon. The purpose of this study was to investigate chronic artery lumen patency as well as histological alteration of artery wall after the short-duration heating balloon dilatation with porcine healthy iliac artery. The short-term heating balloon dilated sites were angiographically patent in acute (1 hour) and in chronic phases (1 and 4 weeks). One week after the dilatation, smooth muscle cells (SMCs) density in the artery media measured from H&E-stained specimens was approx. 20% lower than that in the reference artery. One and four weeks after the dilatations, normal structure of artery adventitia was maintained without any incidence of thermal injury. Normal lamellar structure of the artery media was also maintained. We found that the localized heating restricted to artery media by the short-duration heating could maintain adventitial function and artery normal structure in chronic phase.
    Proc SPIE 02/2012;
  • M. Kunio, N. Shimazaki, T. Arai, M. Sakurada
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    ABSTRACT: We investigated the influences on smooth muscle cells after our novel short-duration thermal angioplasty, Photo-thermo Dynamic Balloon Angioplasty (PTDBA), to reveal the mechanism that can suppress neo-intimal hyperplasia after PTDBA. We obtained the sufficient arterial dilatations by short-duration heating (<=15 s, <70°C) and low dilatation pressure (<0.4 MPa) without arterial injuries in our previous in vivo studies. Smooth muscle cells, which play most important role in chronic treatment effects, were heated during PTDBA and stretch-fixed after PTDBA. The dead cell rate by heating, estimated by Arrhenius equation with A=2.5x1016 s-1 and Ea=1.17×105 J mol-1, was 15.7+/-2.2% after PTDBA. The measured deformation rate of smooth muscle cells' nuclei was 1.6+/-0.1 after PTDBA in vivo. We found that the expression of smooth muscle cells' growth factor after PTDBA was inhibited 0.52 fold compared to that after the conventional balloon angioplasty in vivo. The measured neo-intimal hyperplasia occupancy rate was less than 20% after PTDBA in vivo. We prospect that the inhibition of the growth factor's expression by stretch-fixing may result to suppress the neo-intimal hyperplasia. In addition, the decrease of smooth muscle cells' density in the vessel media by heating might be another reason for the neo-intimal hyperplasia suppression.
    Proc SPIE 02/2012;
  • M Kunio, N Shimazaki, T Arai, M Sakurada
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    ABSTRACT: We investigate the relation between the influences on smooth muscle cells and the chronic performances of our novel short-duration heating balloon dilatation to reveal the heating conditions which can suppress the neo-intimal hyperplasia after our heating dilatations. The temperature of prototype balloon catheter surface was measured during short-duration heating balloon dilatation ex vivo. There existed 2 °C temperature variations in the long direction of prototype balloon catheter at a maximum. The neo-intimal hyperplasia occupancy rate after our short-duration heating dilatations were measured in vivo porcine study. The neo-intimal hyperplasia was suppressed most at 75 °C in balloon peak temperature in vivo. The estimated dead rate of smooth muscle cells at this condition was about 13% by the Arrhenius equation. We think that the suppression of neo-intimal hyperplasia was obtained after our short-duration heating dilatation due to the proper decrease of smooth muscle cells by heating and no thermal damages to the adventitia and surrounding tissues.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2011; 2011:349-52.
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    ABSTRACT: We investigated the effect on smooth muscle cells' proliferation with stretch-fixing in both in vitro and in vivo porcine study to determine the optimum heat condition of novel short-term thermal angioplasty, Photo-thermo Dynamic Balloon Angioplasty (PTDBA). With PTDBA, we have obtained the sufficient arterial dilatation by short-term heating (< 15 s, < 70 °C) and low dilatation pressure (< 0.4 MPa) without excessive neo-intimal hyperplasia on chronic phase. The smooth muscle cells were found to be fixed with stretched shape in vascular wall after PTDBA in vivo. The deformation rate of smooth muscle cells' nuclei was 1.6 +/- 0.1 after PTDBA (15 s, 65 °C, 0.35 MPa). The smooth muscle cells, which were extracted from porcine arteries, were cultured on the specially designed equipment to give stretch-fixing stimulus in vitro. The cell proliferation was inhibited at 20 % stretching compared to 15 % stretching significantly (p < 0.05). The immunostaining specimens of basic Fibroblast Growth Factor (bFGF) and its receptor FGFR-1 were made from the porcine arteries in vivo. We found that the expressions of bFGF and FGFR-1 in the media were not observed after PTDBA. We think that these results suggested the possibility for the inhibition of the excessive cell proliferation after PTDBA.
    Proc SPIE 02/2011;
  • N. Shimazaki, T. Hayashi, M. Kunio, T. Arai
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    ABSTRACT: We have been developing the novel short-term heating angioplasty in which sufficient artery lumen-dilatation was attained with thermal softening of collagen fiber in artery wall. In the present study, we investigated on the relation between the mechanical properties of heated artery and thermal denaturation fractures of arterial collagen in ex vivo. We employed Lumry-Eyring model to estimate temperature- and time-dependent thermal denaturation fractures of arterial collagen fiber during heating. We made a kinetic model of arterial collagen thermal denaturation by adjustment of K and k in this model, those were the equilibrium constant of reversible denaturation and the rate constant of irreversible denaturation. Meanwhile we demonstrated that the change of reduced scattering coefficient of whole artery wall during heating reflected the reversible denaturation of the collagen in artery wall. Based on this phenomenon, the K was determined experimentally by backscattered light intensity measurement (at 633nm) of extracted porcine carotid artery during temperature elevation and descending (25°C-->80°C-->25°C). We employed the value of according to our earlier report in which the time-and temperature- dependent irreversible denaturation amount of the artery collagen fiber that was assessed by the artery birefringence. Then, the time- and temperature- dependent reversible (irreversible) denaturation fraction defined as the reversible ((irreversible) denatured collagen amount) / (total collagen amount) was calculated by the model. Thermo-mechanical analysis of artery wall was performed to compare the arterial mechanical behaviors (softening, shrinkage) during heating with the calculated denaturation fraction with the model. In any artery temperature condition in 70-80°, the irreversible denaturation fraction at which the artery thermal shrinkage started was estimated to be around 20%. On the other hand, the calculated irreversible denaturation fraction remained below 5% and reversible denaturation fraction reached up to 20% while the artery softening occurred without shrinkage. We think that our model of arterial collagen thermal denaturation might be reasonable to estimate the artery mechanical properties during heating.
    Proc SPIE 02/2010;
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    ABSTRACT: We investigated the influences on the smooth muscle cells of temporally heated arterial walls in both ex vivo and in vitro study to determine the optimum heat parameter of novel short-term thermal angioplasty, Photo-thermo Dynamic Balloon Angioplasty (PTDBA). Arterial heating dilatation was performed by the prototype PTDBA balloon ex vivo. We found that the smooth muscle cells in the vessel wall were stretch-fixed after the heating dilatation ex vivo. The stretch-fixing rate of these cells was increased with the temperature rise in the balloon of PTDBA from 60 °C to 70 °C. We measured the proliferation rate of the stretch-fixed smooth muscle cells, which were extracted from porcine arteries, on specially designed culture equipment in vitro. It was observed that the proliferation rate was inhibited at 20 % stretching compared to 10 % stretching. We think the stretch-fixing of the smooth muscle cells might not be harmful for PTDBA performances.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2010; 2010:6706-8.
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    ABSTRACT: We proposed a novel laser-driven short-term heating angioplasty to realize restenosis-suppressive angioplasty for peripheral artery disease. In this study, we investigated the chronic intimal hyperplasia formation after the short-term heating dilatation in vivo, as well as the thermal damage calculation on arterial smooth muscle cells (SMCs). The prototype short-term heating balloon catheter with 5.0, 5.5, 6.0 mm φ in balloon diameter and 25 mm in balloon length were employed. The short-term heating dilatation was performed in porcine iliac arteries with dilatation conditions of 75°C (N=4) and 65°C (N=5) as peak balloon temperature, 18 ± 4s as heating duration, 3.5 atm as balloon dilatation pressure. Four weeks after the balloon dilatation, the balloon-dilated artery segments were extracted and were stained with HE and picrosirius red for histological observation. In the case of 75°C as the peak balloon temperature, neointimal hyperplasia formation was significantly reduced. In this case, the SMCs density in the artery media measured from the HE-stained specimen was 20% lower than that in the reference artery. According to the thermal damage calculation, it was estimated that the SMCs lethality in artery media after the short-term heating angioplasty was 20% in the case of 75°C as the peak balloon temperature. We demonstrated that the short-term heating dilatation reduced the number of SMCs in artery media. We think this SMCs reduction might contribute to the suppression of chronic neointimal hyperplasia.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2010; 2010:1618-21.
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    ABSTRACT: We have studied to develop the new thermal angioplasty methodology, photo-thermo dynamic balloon angioplasty (PTDBA), which provides artery dilatation with short-term (
    Proc SPIE 01/2009;
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    ABSTRACT: We studied on the dilatation characteristics of our new angioplasty, photo-thermo dynamic balloon (PTDB) angioplasty, which provides short-term heating (15s, 50-70 degrees C) dilatation by the combination of laser heat generator and fluid perfusion. In this study, we employed the ex vivo experiments to demonstrate the feasibility of our PTDB angioplasty with extracted porcine carotid artery. Balloon temperature and heating duration were easily controlled with the laser power and irradiation duration. Arterial dilatation was performed with the prototype PTDB catheter (3mm in diameter) ex vivo, sufficient dilation was attained with low dilatation pressure (2atm) that is lower than the limit pressure of elastic region (8atm in this case). The principal of our PTDB angioplasty that was based on the experimental results was dilatation in elastic region, while traditional POBA was accompanied with plastic deformation of artery. It is predicted that successful way of PTDB dilatation was attributed to collagen softening. Collagen coagulation and/or restructure after the heating dilatation might suspend the dilated arterial lumen. We demonstrated the feasibility of our PTDB angioplasty. We think collagen denaturation degree may be the important factor in this methodology.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 02/2008; 2008:3661-3.
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    ABSTRACT: We studied Ho:YAG laser irradiation in blood vessel as a vasodilator ex vivo. We thought that the Ho:YAG laser-induced bubble expansion might be able to dilate the vessel because we found the vessel wall expansion after the Ho:YAG laser irradiation, that is steady deformation, in the vessel ex vivo. There have been many reports regarding to the Ho:YAG laser irradiation in the vessel. Most of studies concentrated on the interaction between Ho:YAG laser irradiation and vessel wall to investigate side effect on Ho:YAG laser angioplasty. We proposed to use the Ho:YAG laser-induced bubble expansion as a vasodilator. We studied vasodilation effect of the Ho:YAG laser-induced bubble ex vivo. The flash lamp excited Ho:YAG laser surgical unit (IH102, NIIC, Japan) (lambda=2.1mum) was used. The laser energy was delivered by a silica glass fiber (outer diameter: 1000mum, core diameter: 600mum). The laser-induced bubble was generated in the extracted fresh porcine carotid artery with the warmed saline perfusion. The laser energy at the fiber tip was ranging from 170-1300mJ per pulse. Number of the laser irradiation was ranged from 20pulses to 100pulses. The outer diameter of the vessel was observed. To examine the change in mechanical properties of the vessel wall, the stress-strain curve of the laser-irradiated vessel was measured. Birefringence observation and microscopic observation of staining specimen were performed. When the laser energy was set to 1300mJ per pulse, the outer diameter of the vessel after the laser irradiation was expanded by 1.4 times comparing with that of before the laser irradiation and the dilatation effect was kept even at 10minutes after the irradiation. The elasticity modulus of the artery by collagen was changed by the laser irradiation. In the polarized microscopic observation, the brightness of the intimal side of the vessel is increased comparing with that of the normal. We think this brightness increasing may be attributed to birefringence change by the arrangement of stretched collagen fiber. We suppose it is likely to be able to use the Ho:YAG laser irradiation as a temporary vasodilater tool in spite of further study should be performed.
    Proc SPIE 03/2007;
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    ABSTRACT: In order to investigate the optimum operation parameters on novel short-term heating (
    Proc SPIE 03/2007;
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    ABSTRACT: Our photo thermal reaction heating architecture balloon realizes less than 10 s short term heating that can soften vessel wall collagen without damaging surrounding tissue thermally. New thermal balloon angioplasty, photo-thermo dynamic balloon angioplasty (PTDBA) has experimentally shown sufficient opening with 2 atm low pressure dilation and prevention of chronic phase restenosis and acute phase thrombus in vivo. Even though PTDBA has high therapeutic potential, the most efficient heating condition is still under study, because relationship of treatment and thermal dose to vessel wall is not clarified yet. To study and set the most efficient heating condition, we have been working on establishment of temperature history estimation method from our previous experimental results. Heating target of PTDBA, collagen, thermally denatures following rate process. Denaturation is able to be quantified with measured collagen birefringence value. To express the denaturation with equation of rate process, the following ex vivo experiments were performed. Porcine extracted carotid artery was soaked in two different temperature saline baths to enforce constant temperature heating. Higher temperature bath was set to 40 to 80 degree Celsius and soaking duration was 5 to 40 s. Samples were observed by a polarizing microscope and a scanning electron microscope. The birefringence was measured by polarizing microscopic system using Brace-Koehler compensator 1/30 wavelength. The measured birefringence showed temperature dependency and quite fit with the rate process equation. We think vessel wall temperature is able to be estimated using the birefringence changes due to thermal denaturation.
    Proc SPIE 03/2007;
  • N. Shimazaki, H. Tokunaga, T. Arai, M. Sakurada
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    ABSTRACT: We have proposed a new thermal angioplasty device, Photo-thermo dynamic balloon (PTDB), for stenotic artery treatment. The PTDB provides short-term (
  • Natsumi Shimazaki, Tsunenori Arai, Masami Sakurada
    Journal of Vascular and Interventional Radiology - J VASC INTERVEN RADIOL.