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We investigated the delivery of rhodamine B and Oregon Green ®-labeled paclitaxel (OGLP) in ex vivo porcine carotid artery wall (CAW) samples after heating the reagents to 50-70 C for 15 s. When the isolated CAW samples were placed in the heated uorophore solutions, the penetration depth of the hydrophobic rhodamine B increased signi cantly compared with reference solution at 37 C. The penetration depth of OGLP also tended to increase upon heating to 70 C for 15 s. We also studied the mechanism of this agent delivery enhancement by observing the inner surface structure and hydrophobicity of the CAW samples after heating. An expanded mesh structure at the inner surface of the heated CAW samples was observed upon heating above 70 C, and the mean hydrophobicity of the media layer also increased signi cantly. We hypothesize that heating at 60-70 C for 15 s enhances the delivery of uorophores to CAW samples as a result of an expanded mesh structure at the inner surface of the CAW, along with a simultaneous increase in hydrophobicity.

We studied the effects of interactive pressure on the delivery of hydrophobic rhodamine B to ex vivo heated artery walls to determine the optimal drug delivery conditions. The heated artery samples, which were maintained at 63 C on the intimal surface, were prepared by heating for 15 s. Interactive pressure up to 10 atm was directly applied with a rhodamine B solution to the artery samples from the intima side over 30 s. The uorescence brightness distribution of rhodamine B in the samples were measured microscopically to investigate the quantity and depth of drug delivery. We found a decrease in the depth of drug delivery in the heated artery samples compared with the reference artery samples. This decrease in drug delivery depth may have resulted from increased hydrophobic binding of rhodamine B at the intima because of heating. We also found a signi cant increase in quantity of drug delivery at a certain interactive pressure in the heated artery samples. Hematoxylin-eosin staining of cross sections of pressurized heated artery samples revealed delamination of the intima and extension of the internal elastic lamina. We hypothesize that the dependence of drug delivery quantity on the interactive pressure is attributed to morphological changes in the intima and the internal elastic lamina.

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.

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