Inhibition of intimal hyperplasia in balloon injured arteries with adjunctive phthalocyanine sensitised photodynamic therapy

Eur J Vasc Endovasc Surg. 1996 Jan;11(1):19-28. doi: 10.1016/s1078-5884(96)80130-4.

Abstract

Objectives: We investigated the effects of Photodynamic therapy (PDT) using Aluminium disulphonated phthalocyanine (AlS2Pc) on experimental intimal hyperplasia (FCIH).

Materials and 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.

Chief outcome measures: (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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty, Balloon / adverse effects*
  • Animals
  • Carotid Arteries / metabolism
  • Carotid Arteries / pathology
  • Carotid Arteries / radiation effects
  • Carotid Artery Injuries*
  • Hyperplasia / etiology
  • Indoles / pharmacokinetics
  • Indoles / pharmacology*
  • Laser Therapy
  • Male
  • Organometallic Compounds / pharmacokinetics
  • Organometallic Compounds / pharmacology*
  • Photochemotherapy*
  • Radiation-Sensitizing Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Tunica Intima / pathology*
  • Tunica Intima / radiation effects
  • Wounds and Injuries / drug therapy
  • Wounds and Injuries / radiotherapy

Substances

  • Indoles
  • Organometallic Compounds
  • Radiation-Sensitizing Agents
  • aluminum phthalocyanine disulfonate