Gm. Lamuraglia et al., PHOTODYNAMIC THERAPY INHIBITS EXPERIMENTAL ALLOGRAFT-REJECTION - A NOVEL-APPROACH FOR THE DEVELOPMENT OF VASCULAR BIOPROSTHESES, Circulation, 92(7), 1995, pp. 1919-1926
Background Biological vascular allografts have proved unsatisfactory b
ecause of thrombosis, occlusion, and aneurysmal degeneration during ch
ronic rejection. Photodynamic therapy (PDT), a technique that leads to
the production of cytotoxic free radicals, was investigated as a nove
l method to prepare arterial allografts. Methods and Results Shortly a
fter impregnation with the photosensitizer drug chloroaluminum sulfona
ted phthalocyanine, infrarenal aortas of ACI rats were PDT-treated and
orthotopically grafted in Lewis rats (PDT). The transplanted grafts w
ere sequentially analyzed at 2, 4, and 8 weeks by morphometry, immunoh
istochemistry, and scanning electron microscopy. Of 25 untreated allog
rafts, 4 (16%) developed aneurysms compared with 0 of 33 in PDT or unt
reated isografts (ISO, P<.001). PDT treatment of allografts significan
tly inhibited intimal hyperplasia (P<.001) and resulted in intimal are
as comparable to those in ISO. However, medial thickness in both contr
ol allografts and PDT grafts was markedly decreased compared with ISO.
External graft diameters of control allografts at 8 weeks were signif
icantly enlarged (P<.02) coma pared with PDT or ISO. At all time point
s, T lymphocytes were found in a substantially larger number in untrea
ted 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 findin
gs suggest that local PDT treatment of arterial allografts inhibits in
flammatory infiltration, aneurysmal dilatation, and development of int
imal hyperplasia and may be used to develop vascular bioprostheses for
use in humans.