Inhibition of intimal hyperplasia in balloon injured arteries with adjunctive phthalocyanine sensitised photodynamic therapy.
OBJECTIVE
We investigated the effects of Photodynamic therapy (PDT) using Aluminium disulphonated phthalocyanine (AlS2Pc) on experimental intimal hyperplasia (FCIH).


METHODS
(a) Pharmacokinetics: Normal rats were injected with Als2Pc and carotid artery fluorescence was measured. (b) Normal artery PDT: Sensitised rats underwent carotid artery laser irradiation (50J/cm2, 675nm) and were assessed after 3 and 14 days and 1-6 months. (c) PDT: Rats underwent standard carotid artery balloon injury immediately prior to PDT and arteries were assessed at 2 to 26 weeks, together with laser, AlS2Pc, and untreated controls.


METHODS
(a) Fluorescence intensity in different arterial layers. (b) Medial smooth muscle cell counts per high power field (light microscopic). (c) Percentage amount of FCIH (area of intimal hyperplasia) as a ratio of the IEL (area enclosed by the internal elastic lamina).


RESULTS
(a) AlS2Pc fluorescence intensity increased with increasing dosage, with maximal fluorescence in the arterial media at 30 min. (b) PDT produced medial cell depletion at 3 days and persisted over 6 months without loss of vessel integrity. (c) PDT completely inhibited FCIH at 2 and 4 weeks. This was partial at 6 to 26 weeks (51% of untreated level). PDT inhibition of FCIH was significantly greater than in any of the control groups. p < 0.0001. Mann-Whitney Test.


CONCLUSIONS
Adjunctive AlS2Pc sensitised photodynamic therapy inhibits experimental intimal hyperplasia, by causing medial smooth muscle cell depletion. This offers a new approach to the management of angioplasty restenosis in patients.
Nyamekye
I
I
Department of Surgery, University College London Medical School, Rayne Institute, U.K.
Buonaccorsi
G
G
McEwan
J
J
MacRobert
A
A
Bown
S
S
Bishop
C
C
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D020212:Carotid Artery Injuries; D006965:Hyperplasia / Q000209:etiology; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D053685:Laser Therapy; D008297:Male; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017539:Tunica Intima / Q000473:pathology* / Q000528:radiation effects; D014947:Wounds and Injuries / Q000188:drug therapy / Q000532:radiotherapy
D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C064331:aluminum phthalocyanine disulfonate