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


METHODS
rats (n=90) were subdivided into 4 main groups. In the experimental group (n=36: 3 replications x 4 doses x 3 examination time-points), ALA was administered (200mg/kg i.v.) 2-3h before balloon injury (BI) of the common iliac artery followed by endovascular illumination with 633nm at either 12.5, 25, 50 or 100J/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+/-0.12mm(2) (BI), 0.27+/-0.12mm(2) (BI+LO at 100J/cmdl) in contrast to 0.02+/-0.02mm(2) after BI+PDT at 100J/cmdl 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.


CONCLUSIONS
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 50-100J/cmdl.
D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000627:therapeutic use*; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D003251:Constriction, Pathologic / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006965:Hyperplasia / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology / Q000601:surgery*
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid