Endovascular photodynamic therapy with aminolaevulinic acid prevents balloon induced intimal hyperplasia and constrictive remodelling

Background and Objective: Intimal hyperplasia (IH) and constrictive remodelling are important causes of restenosis following endovascular interventions, such as percutaneous transluminal angioplasty. Photodynamic therapy (PDT) with 5-aminolaevulinic (ALA) may prevent restenosis by cellular depletion and the elimination of cholinergic innervation. Study design/Materials and Methods: Rats (n = 90) were subdivided into 4 main groups. In the experimental group (n = 36: 3 replications × 4 doses × 3 examination time-points), ALA was administered (200mg/kg i.v.) 2-3 h before balloon injury (BI) of the common iliac artery followed by endovascular illumination with 633 nm at either 12.5, 25, 50 or 100 J/cm diffuser length (dl BI + PDT group). As control groups served the BI + Light only (LO) group (n = 36) that received no ALA, the BI only group (n = 9) (BI), and a group (n = 9) that received a Sham procedure (Sham group). Results: Planimetric analysis showed IH of 0.28 ± 0.12 mm2 (BI), 0.27 ± 0.12 mm2 (BI+ LO at 100 J/cm dl) in contrast to 0.02 ± 0.02 mm2 after BI + PDT at 100J/cm dl at 16 weeks (p < 0.05). In the BI + PDT groups, a light-dose increase of a factor 2 led to an IH decrease of 17% (p < 0.05). In the BI and BI + LO groups constrictive remodelling was found, in contrast to BI + PDT treated groups at 16 weeks. The staining of cholinergic innervation of the tunic media of the blood vessel wall in BI + PDT showed no damage at the highest fluence. Conclusion: Endovascular ALA-PDT prevents IH and constrictive remodelling after BI without damage of cholinergic innervation of the tunica media. The effective light fluence rate in the rat is 50-100 J/cm dl.

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