TY - JOUR
T1 - Photodynamic therapy inhibits experimental allograft rejection
T2 - A novel approach for the development of vascular bioprostheses
AU - LaMuraglia, Glenn M.
AU - Adili, Farzin
AU - Schmitz-Rixen, Thomas
AU - Michaud, Norman A.
AU - Flotte, Thomas J.
PY - 1995/10/1
Y1 - 1995/10/1
N2 - Background: Biological vascular allografts have proved unsatisfactory because of thrombosis, occlusion, and aneurysmal degeneration during chronic rejection. Photodynamic therapy (PDT), a technique that leads to the production of cytotoxic free radicals, was investigated as a novel method to prepare arterial allografts. Methods and Results: Shortly after impregnation with the photosensitizer drug chloroaluminum sulfonated phthalocyanine, infrarenal aortas of ACI rats were PDT-treated and orthotopically grafted in Lewis rats (PDT). The transplanted grafts were sequentially analyzed at 2, 4, and 8 weeks by morphometry, immunohistochemistry, and scanning electron microscopy. Of 25 untreated allografts, 4 (16%) developed aneurysms compared with 0 of 33 in PDT or untreated isografts (ISO, P<.001). PDT treatment of allografts significantly inhibited intimal hyperplasia (P<.001) and resulted in intimal areas comparable to those in ISO. However, medial thickness in both control allografts and PDT grafts was markedly decreased compared with ISO. External graft diameters of control allografts at 8 weeks were significantly enlarged (P<.02) compared with PDT or ISO. At all time points, T lymphocytes were found in a substantially larger number in untreated control grafts than in PDT or ISO. Scanning electron microscopy at 4 weeks confirmed complete repopulation with endothelial cells in PDT, which was not seen in the control allografts. Conclusions: Our findings suggest that local PDT treatment of arterial allografts inhibits inflammatory infiltration, aneurysmal dilatation, and development of intimal hyperplasia and may he used to develop vascular bioprostheses for use in humans.
AB - Background: Biological vascular allografts have proved unsatisfactory because of thrombosis, occlusion, and aneurysmal degeneration during chronic rejection. Photodynamic therapy (PDT), a technique that leads to the production of cytotoxic free radicals, was investigated as a novel method to prepare arterial allografts. Methods and Results: Shortly after impregnation with the photosensitizer drug chloroaluminum sulfonated phthalocyanine, infrarenal aortas of ACI rats were PDT-treated and orthotopically grafted in Lewis rats (PDT). The transplanted grafts were sequentially analyzed at 2, 4, and 8 weeks by morphometry, immunohistochemistry, and scanning electron microscopy. Of 25 untreated allografts, 4 (16%) developed aneurysms compared with 0 of 33 in PDT or untreated isografts (ISO, P<.001). PDT treatment of allografts significantly inhibited intimal hyperplasia (P<.001) and resulted in intimal areas comparable to those in ISO. However, medial thickness in both control allografts and PDT grafts was markedly decreased compared with ISO. External graft diameters of control allografts at 8 weeks were significantly enlarged (P<.02) compared with PDT or ISO. At all time points, T lymphocytes were found in a substantially larger number in untreated control grafts than in PDT or ISO. Scanning electron microscopy at 4 weeks confirmed complete repopulation with endothelial cells in PDT, which was not seen in the control allografts. Conclusions: Our findings suggest that local PDT treatment of arterial allografts inhibits inflammatory infiltration, aneurysmal dilatation, and development of intimal hyperplasia and may he used to develop vascular bioprostheses for use in humans.
KW - allografts
KW - arteries
KW - free radicals
KW - photodynamic therapy
KW - rejection
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U2 - 10.1161/01.CIR.92.7.1919
DO - 10.1161/01.CIR.92.7.1919
M3 - Article
C2 - 7671376
AN - SCOPUS:0029102862
SN - 0009-7322
VL - 92
SP - 1919
EP - 1926
JO - Circulation
JF - Circulation
IS - 7
ER -