Jenkins, Michael Philip; (1999) The prevention of arterial restenosis using endovascular photodynamic therapy. Masters thesis (M.S), UCL (University College London).

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Abstract

Atherosclerosis is the commonest aetiology in deaths arising from cardiovascular disease. It is characterised by the build up of an intraluminal plaque leading to arterial stenosis. Balloon angioplasty offers a minimally invasive method of dilating such stenoses in both peripheral and coronary arteries. However, despite very favourable immediate results, 15-40% of arteries restenose within 3-6 months following angioplasty with obvious clinical and resource implications. Restenosis is caused by a combination of neointimal hyperplasia (NIH) and negative geometric remodelling, the combined effect of which results in luminal narrowing. The aim of this thesis was to investigate a method of inhibiting restenosis using photodynamic therapy (PDT). PDT involves the interaction of light of a specific wavelength with a pre-administered photosensitiser to produce cell death by oxygen-dependent cytotoxic mediators. Experimental project Preliminary studies established the pharmacokinetics of the chosen photosensitiser 5-aminolaevulinic acid (ALA) in a swine model. From these experiments the optimum drug-light interval was calculated and in a second study, PDT was applied to normal porcine iliac and coronary arteries using an endovascular light source. Depletion of medial vascular smooth muscle cells (VSMC) was seen at 3 and 14 days and was found to be partially dependent on the drug-light interval. Finally, iliac and coronary arteries were balloon injured and then treated with PDT or sham illumination. Histomorphometric studies following harvest at 28 days showed less NIH and less negative remodelling in the group treated with PDT. Clinical project A clinical pilot study of angioplasty with adjuvant PDT was commenced. Patients deemed to be at high risk of restenosis underwent femoral angioplasty followed by endovascular PDT and were followed up by duplex and digital subtraction angiography at 6 months. The results of this small study would suggest that PDT is successful in inhibiting restenosis, but this now needs to be confirmed in a randomised controlled trial.

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