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Cytotoxicity of Aluminum Phthalocyanine on Intimal Hyperplasia

Darwin Eton, MD; Martin Borhani, MD; Kenneth Spero, MD; Raymond A. Cava, MD; Leonard Grossweiner, PhD; Samuel S. Ahn, MD

Arch Surg. 1995;130(10):1098-1103.

Abstract
Objective
To study the cytotoxic effect of photodynamic therapy (PDT) on myointimal hyperplasia (MIH) in 120 New Zealand white rabbits using the chromophore chloroaluminum phthalocyanine tetrasulfonate (APtS).

Design
A common carotid artery (CCA) injury model was used to initiate MIH. Photodynamic therapy was administered 1 week after injury (inhibition arm) or 6 weeks after injury (treatment arm). The inhibition arm CCAs were harvested 6 weeks after therapy. The treatment arm CCAs were harvested 1 week or 6 weeks after therapy. Each evaluation included four subgroups (n=10 each): control, drug only, laser only, and drug plus laser.

Interventions
An established CCA balloon injury model was used. Photodynamic therapy was administered by exposing CCAs to continuous external laser irradiation 30 minutes after treatment with a 2.5mg/kg intravenous dose of APtS (fluence=25 J/cm², =672 nm). The control and drug-only subgroups received sham reoperations without laser exposure.

Main Outcome Measures
Following harvest, the CCAs were evaluated for area of stenosis and cell density.

Results
In the inhibition arm, no PDT effect was seen on intimal cell density or area stenosis. In the treatment arm, intimal cell density was markedly diminished (P<.05) in the rabbits in the drug-laser group that were killed 1 week but not 6 weeks after PDT compared with rabbits in the control, drug-only, and laser-only groups. Area stenosis was not significantly affected by PDT.

Conclusions
Marked acute cytotoxicity of PDT on MIH was verified in vivo in the treatment arm. No sustained benefit of PDT was seen in the inhibition or the treatment arms. Refinements in dosimetry will be necessary to acheive long-term benefit of PDT for MIH.

(Arch Surg. 1995;130:1098-1103)

Author Affiliations
From the Departments of Surgery, University of Illinois at Chicago (Drs Eton, Borhani, Spero, and Cava) and University of California, Los Angeles (Dr Ahn); and the Wenske Laser Institute of Ravenswood Hospital, Chicago, Ill (Dr Grossweiner).

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