Photodynamic therapy inhibits experimental allograft rejection. A novel approach for the development of vascular bioprostheses.
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.


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 be used to develop vascular bioprostheses for use in humans.
LaMuraglia
G M
GM
Department of Pathology, Massachusetts General Hospital, Boston 02114, USA.
Adili
F
F
Schmitz-Rixen
T
T
Michaud
N A
NA
Flotte
T J
TJ
D000535:Aluminum / Q000627:therapeutic use; D000818:Animals; D001012:Aorta, Abdominal / Q000637:transplantation* / Q000648:ultrastructure; D001705:Bioprosthesis; D001807:Blood Vessel Prosthesis; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D007211:Indoles / Q000627:therapeutic use; D008855:Microscopy, Electron, Scanning; D009942:Organometallic Compounds / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C052736:chloroaluminum tetrasulfophthalocyanine; D000535:Aluminum