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Local Infusion of the Nitric oxide Donor Sin-1 After Angioplasty

Effects on intimal hyperplasia in porcine coronary arteries

Authors


Jan Harnek, Heart Radiology, Heart Lung Division, University Hospital SE-22185 Lund, Sweden.
FAX +46 46 211 69 56.
E-mail: jan.harnek@skane.se

Abstract

Purpose:  To investigate the development of intimal hyperplasia in response to percutaneous transluminal coronary angioplasty (PTCA) followed by local delivery of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1).

Material and Methods:  Overdilation PTCA was performed in coronary arteries in 20 healthy pigs. One of the dilated segments was additionally treated with local delivery of SIN-1 for 10 min. Segments distal to the treated part of the arteries served as controls. Arteries were radiographically depicted and analyzed after 1 and 8 weeks for actin, myosin and intermediate filaments (IF), nitric oxide synthetase (NOS) and histological evaluation.

Results:  Segments treated with PTCA+SIN-1 showed a significantly (p = 0.03) larger luminal diameter compared with PTCA only treated segments. The luminal loss after SIN-1 was not significant compared with the diameter prior to treatment. Endothelial NOS content was significantly lower in the PTCA+SIN-1 group compared with the PTCA group after 1 (p = 0.03) and 8 weeks (p = 0.013). IF/actin ratio after 1 week was significantly increased in PTCA-treated segments compared with untreated controls (p = 0.004), and compared with PTCA+SIN-1-treated segments (p = 0.004).

Conclusion:  PTCA-induced intimal hyperplasia was potently inhibited by local delivery of the NO donor SIN-1. Momentary events at the time of injury play a significant role in the development of intimal hyperplasia and long-lasting down-regulation of the endothelial NOS expression after SIN-1 exposure is suggested. The IF/actin ratio can be useful as an early marker of intimal hyperplasia.

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