TY - JOUR
T1 - Photodynamic therapy of arteries
T2 - A novel approach for treatment of experimental intimal hyperplasia
AU - Ortu, P.
AU - LaMuraglia, G. M.
AU - Roberts, W. G.
AU - Flotte, T. J.
AU - Hasan, T.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1992
Y1 - 1992
N2 - Background. Photodynamic therapy (PDT) uses light activation of otherwise nontoxic dyes for the production of reactive oxygen species that cause cell injury and death. Methods and Results. The inhibition of intimal hyperplasia (IH) by PDT was studied in the balloon injury model of the rat carotid artery. Chloroaluminum-sulfonated phthalocyanine (CASPc) was the drug chosen for PDT because it does not produce skin photosensitivity and has a high absorption peak of light at 675 nm, a wavelength with good tissue penetration. A pilot study indicated that CASPc administration with laser radiant exposure of 100 J/cm2 resulted in a homogeneous, circumferential effect on the whole artery. Male Sprague-Dawley rats received the balloon catheter injury to the left common carotid artery (day 0) and were equally divided into two groups. Nine rats received either CASPc (5 mg/kg i.v., n=6) or saline (n=3) at day 2, before IH was present, and nine rats received CASPc or saline in the same manner on day 7, when IH was already present. Twenty minutes after drug injection, the distal left common carotid artery was irradiated under saline with 675-nm laser light at 100 mW/cm2 for 103 seconds (100 J/cm2). At this low laser irradiance, there are no thermal effects, but photoactivation of CASPc occurs. The rats were killed at day 14 after balloon injury when IH reaches a maximum. The arteries were harvested after perfusion-fixation for light microscopy, histological and computerized morphometric evaluation, and transmission electron microscopy (TEM) analysis. The cross-sectional areas of the neointima were measured in the PDT-treated arteries and in the laser-only control arteries. There was a significant mean±SD decrease of IH in the PDT-irradiated segments of the arteries (0.06±0.05 mm2) versus the laser-only control ones (0.17±0.07 mm2) (t test, p<0.001), with no statistical difference between the day 2 and day 7 treated rats. Lack of IH was correlated in 90% of cases with histological absence of medial smooth muscle cells or inflammatory cells, but no other structural injury was identified. TEM analysis showed early evidence of PDT- mediated cytotoxic effects at 4 hours and the absence of collagen or elastic tissue structural alterations. Conclusions. These data demonstrated that PDT can effectively inhibit the IH response when it is used before or during induction of cellular proliferation in this acute model. Although the long- term implications of PDT in arteries need to be defined, this technique may offer a new method for understanding and treating IH.
AB - Background. Photodynamic therapy (PDT) uses light activation of otherwise nontoxic dyes for the production of reactive oxygen species that cause cell injury and death. Methods and Results. The inhibition of intimal hyperplasia (IH) by PDT was studied in the balloon injury model of the rat carotid artery. Chloroaluminum-sulfonated phthalocyanine (CASPc) was the drug chosen for PDT because it does not produce skin photosensitivity and has a high absorption peak of light at 675 nm, a wavelength with good tissue penetration. A pilot study indicated that CASPc administration with laser radiant exposure of 100 J/cm2 resulted in a homogeneous, circumferential effect on the whole artery. Male Sprague-Dawley rats received the balloon catheter injury to the left common carotid artery (day 0) and were equally divided into two groups. Nine rats received either CASPc (5 mg/kg i.v., n=6) or saline (n=3) at day 2, before IH was present, and nine rats received CASPc or saline in the same manner on day 7, when IH was already present. Twenty minutes after drug injection, the distal left common carotid artery was irradiated under saline with 675-nm laser light at 100 mW/cm2 for 103 seconds (100 J/cm2). At this low laser irradiance, there are no thermal effects, but photoactivation of CASPc occurs. The rats were killed at day 14 after balloon injury when IH reaches a maximum. The arteries were harvested after perfusion-fixation for light microscopy, histological and computerized morphometric evaluation, and transmission electron microscopy (TEM) analysis. The cross-sectional areas of the neointima were measured in the PDT-treated arteries and in the laser-only control arteries. There was a significant mean±SD decrease of IH in the PDT-irradiated segments of the arteries (0.06±0.05 mm2) versus the laser-only control ones (0.17±0.07 mm2) (t test, p<0.001), with no statistical difference between the day 2 and day 7 treated rats. Lack of IH was correlated in 90% of cases with histological absence of medial smooth muscle cells or inflammatory cells, but no other structural injury was identified. TEM analysis showed early evidence of PDT- mediated cytotoxic effects at 4 hours and the absence of collagen or elastic tissue structural alterations. Conclusions. These data demonstrated that PDT can effectively inhibit the IH response when it is used before or during induction of cellular proliferation in this acute model. Although the long- term implications of PDT in arteries need to be defined, this technique may offer a new method for understanding and treating IH.
KW - hyperplasia
KW - intima
KW - photodynamic therapy
KW - phthalocyanines
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U2 - 10.1161/01.CIR.85.3.1189
DO - 10.1161/01.CIR.85.3.1189
M3 - Article
C2 - 1537115
AN - SCOPUS:0026507462
VL - 85
SP - 1189
EP - 1196
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 3
ER -