Reduction in the response to coronary and iliac artery injury with photodynamic therapy using 5-aminolaevulinic acid.
OBJECTIVE
Photodynamic therapy (PDT) uses red light (non-thermal, non-ionising) to activate a previously administered photosensitizing drug. This inhibits neointimal hyperplasia in injured arteries in small animals where it appears safe and well tolerated. Our aim was to develop a method for percutaneous application of PDT to iliac and coronary arteries in a large animal model and investigate its influence on the remodeling and intimal hyperplastic response to balloon injury.


METHODS
Studies were undertaken on 13 juvenile Large White-Landrace crossbred pigs (15-20 kg). After intravenous administration of the photosensitizing agent 5-amino laevulinic acid (ALA), the arterial tree was accessed via the left common carotid artery and balloon injuries made by over-distension in both common iliacs (thirteen animals) and one or two main coronary arteries (eight animals). Half the injured sites were then illuminated with red laser light transmitted via the catheter. Animals were culled 28 days later and tissue harvested for histomorphometry.


RESULTS
Compared with control injured vessels, PDT treated, balloon injured coronary arteries had a larger lumen (1.4 vs. 0.8 mm2, P = 0.002), larger area within the external elastic lamina (2.8 vs. 2.2 mm2, P = 0.006) and smaller area of neointimal hyperplasia (0.4 vs. 0.7 mm2, P = 0.06), 28 days after intervention. Less neointimal hyperplasia and the absence of negative remodeling resulted in the lumen of PDT-treated, injured segments being the same as that of adjacent reference segments (1.5 vs. 1.6 mm2). Similar trends, but with smaller differences, were seen in the iliac vessels.


CONCLUSIONS
Intra-arterial, trans-catheter PDT favourably influences the arterial response to balloon injury in both the coronary and peripheral circulations. This technique offers a promising new approach to restenosis after endovascular procedures.
Jenkins
M P
MP
Department of Surgery, Royal Free and University College Medical School, London, UK.
Buonaccorsi
G A
GA
Mansfield
R
R
Bishop
C C
CC
Bown
S G
SG
McEwan
J R
JR
D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D003327:Coronary Disease / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D007083:Iliac Artery / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D013552:Swine
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid