ABSTRACT

This PhD dissertation consists of three articles and an overview. The experiments were performed at the Institute of Experimental Clinical Research, Aarhus University, and at the Department of Cardiology, Skejby Sygehus, Aarhus, Denmark.

Restenosis after percutaneous coronary intervention remains a major problem in interventional cardiology. Restenosis is caused by a combination of neointima formation (scar tissue) and constrictive vascular remodelling (circumferential shrinkage).

A porcine restenosis model was developed in which all experiments were performed.

The aim of the first study was to examine whether thrombus organization was a major component of late neointimal formation after deep vascular injury. We showed that the maximal thrombus size was at least four times smaller than late neointima formation and concluded that thrombus organization plays no major role in late neointimal formation.

In the second study we sought to examine the validity of in vivo angioscopy to observe coronary thrombi. In comparison to histopathology, angioscopic detection of thrombus had high sensitivity and negative predictive value but low-to-moderate specificity and positive predictive value. Visual assessment of colour of thrombi observed by angioscopy did not reflect histologic morphology of thrombus according to the definitions used in this study.

The purpose of the third study was to examine whether centered catheter-based β -radiation would be superior to eccentric radiation with regard to inhibition of in-stent neointima formation in stented porcine arteries. In order to avoid radiation-induced stent edge stenosis, the study was designed so that geographical miss (i.e., inadequate coverage of the injured segment) was avoided. We showed that a centered radiation source significantly reduced in-stent neointima formation as compared to an eccentrically placed source and no radiation. This effect on in-stent neointima formation occurred at the expense of delayed intimal healing and stent malapposition. Despite avoiding geographical miss, we found that catheter-based radiation induced stent edge stenosis.

Recent studies with drug-eluting stents have shown very low incidences of restenosis. It seems very likely that drug-eluting stents will almost eliminate restenosis in the future. Currently, further studies are needed to evaluate new drug-eluting stents and to compare them with existing drug-eluting stents. Finally, we need to examine the cause of restenosis after drug-eluting stent implantation in order to be able to reduce the current rate of restenosis even further.