Intracoronary photodynamic therapy reduces neointimal growth without suppressing re-endothelialisation in a porcine model.
OBJECTIVE
To examine the effects of intracoronary PhotoPoint photodynamic therapy (PDT) with a new photosensitiser, MV0611, in the overstretch balloon and stent porcine models of restenosis.


METHODS
28 pigs were injected with 3 mg/kg of MV0611 systemically 4 h before the procedure. Animals were divided into either the balloon overstretch injury (BI) group (n = 19) or the stented group (n = 9). After BI, a centred delivery catheter was positioned in the artery to cover the injured area, and light (532 nm, 125 J/cm(2)) was applied to activate the drug (n = 10). Control arteries (n = 9) were not activated by light. In the stented group, the drug was light activated before stent deployment. Serial sections of vessels were processed 14 days after treatment in the BI group and 30 days after treatment in the stented group for histomorphometric or immunohistochemical analysis.


RESULTS
Intracoronary PDT significantly reduced intimal thickness in both BI and stented arteries (about 65%: 0.22 (SEM 0.05) mm v 0.62 (0.05) mm, p < 0.01; and about 26%: 0.40 (0.04) mm v 0.54 (0.04) mm, p < 0.01, respectively). PDT increased luminal area by <or= 60% and 50% within BI and stented arteries (3.43 (0.27) mm(2)v 5.51 (0.52) mm(2), p < 0.05; 4.0 (0.02) mm(2)v 6.0 (0.16) mm(2), p < 0.01), respectively. Complete re-endothelialisation was observed by immunohistochemical and gross histological analyses in all PDT and control arteries. There were no cases of aneurysm formation or thrombosis.


CONCLUSIONS
Intracoronary PhotoPoint PDT with MV0611 reduces intimal proliferation without suppressing re-endothelialisation in a porcine model of restenosis.
Waksman
R
R
Division of Cardiology, Washington Hospital Center, Washington, DC, USA. ron.waksman@medstar.net
Leitch
I M
IM
Roessler
J
J
Yazdi
H
H
Seabron
R
R
Tio
F
F
Scott
R W
RW
Grove
R I
RI
Rychnovsky
S
S
Robinson
B
B
Pakala
R
R
Cheneau
E
E
D000800:Angioplasty, Balloon; D000818:Animals; D049109:Cell Proliferation; D023903:Coronary Restenosis / Q000517:prevention & control*; D003331:Coronary Vessels / Q000293:injuries; D005240:Feasibility Studies; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008652:Mesoporphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011897:Random Allocation; D015607:Stents; D013552:Swine; D017539:Tunica Intima
C532479:MV0611 compound; D008652:Mesoporphyrins; D017319:Photosensitizing Agents