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It has been shown repeatedly in animal and clinical studies that heparin coating reduces thrombotic complications of several surfaces in contact with flowing blood. The demonstration that implantation of heparin-coated coronary stents is also effective in prevention of subacute thrombotic occlusion in a pig model offers the perspective of a clinical role of this treatment too. In order to put this to the test, the Benestent II pilot trial has been designed. This study will be conducted in a stepwise fashion in order to explore the feasibility of delaying deep anticoagulation as much as possible. Therefore, the primary goal is to minimize or exclude the need for heparin treatment following stent implantation. In addition, the effects on the need for revascularization procedures during follow-up will be recorded as well as the late morphological consequences as measured with quantitative coronary angiography.

Atherosclerotic cardiovascular disease remains one of the most important causes of morbidity and mortality in the industrialized world. Treatment is basically aimed at palliation and consists of either pharmacological intervention or revascularization. The first significant advances in the latter were largely surgical. However, the pressing need for treatment with less invasive and potentially less expensive techniques, have stimulated the development of nonsurgical revascularization techniques. Percutaneous transluminal coronary balloon angioplasty, which was first performed by Andreas Gruentzig in 1977, is one of the most successful examples and provided the stimulus for a rapid technological growth of interventional cardiology. It is now widely accepted as a safe and effective treatment of obstructive coronary artery disease. However, the risk of abrupt vessel closure during or immediately after the intervention and the risk of late luminal renarrowing or restenosis continue to compromise its overall safety and efficacy. To improve the immediate and long-term results of balloon angioplasty, a number of new technologies such as intracoronary stenting, directional or rotational atherectomy, and laser therapy have been developed and represent the leading edge in the battle against atherosclerosis. The purpose of this paper is to review the experience and results of the various types of stents in clinical use.

A polyethylene-terephthalate braided mesh stent has been developed for application in the (coronary) arterial tree. In vitro measurements showed that the radial pressure delivered by this device was in the same range as that of a stainless steel stent. Hysteresis-like behavior, however, occurred after constraining the polyester stent for a period of only 15 minutes on a delivery system for percutaneous implantation. This implies that the polymer stent must be mounted on this delivery system immediately before the placement procedure, and that either a diameter in the unconstrained condition must be selected, which is considerably larger than the diameter of the target vessel, or stent expansion has to be enhanced by balloon expansion. Taking into account the results obtained during the in vitro studies, we investigated the angiographic patency and histologic features after implantation of this polyester stent in peripheral arteries of pigs. In four animals eight stents were placed. Except for heparin during the implantation procedure only, antithrombotic or antiplatelet drugs were not administered. After 4 weeks repeat angiography was performed. Angiography revealed that five of the six correctly placed stents were patent. At autopsy, two additional patent stents proved to be located in the aortic bifurcation, probably due to failure of the delivery system. Quantitative assessment showed that the mean luminal diameters of the site of stent placement were 3.3 +/- 0.2 mm before, 3.2 +/- 0.2 mm immediately after, and 3.1 +/- 0.3 mm at 4 weeks after implantation. Histology demonstrated an inflammatory reaction of variable severity around the stent fibers. Quantitative histologic measurements showed that the thickness of the neointima was 114 +/- 38 mum after 4 weeks. In conclusion, polyester stents can be constructed with mechanical properties similar to stainless steel stents. Hysteresis-like behavior of polyester stents, however, influences the selection of the nominal stent diameter as well as the forces exerted to the vessel wall. After implantation in porcine peripheral arteries, five of six correctly placed stents were patent at 4 weeks. The extent of neointimal proliferation was similar to that observed after placement of metal stents in swine, despite the presence of a more pronounced inflammatory reaction.

The immediate changes in stenosis geometry following Wallstent and Wiktor stent implantation in native coronary arteries were compared in 92 patients (46 in each group) using automated edge detection. Patients with comparable baseline stenosis characteristics were selected. Lesions were matched for lesion site, reference diameter, and minimal luminal diameter. In both groups, the stented coronary artery was the left anterior descending artery in 27 patients (59%), the left circumflex artery in four patients (9%), and the right coronary artery in 15 patients (33%). The baseline reference diameter was 2.86 +/- 0.39 mm and 2.87 +/- 0.42 mm in the Wallstent and Wiktor stent study group, respectively (NS). The baseline minimal luminal diameter was identical in both groups (1.13 +/- 0.24 mm). The nominal size (mean +/- SD) of the unconstrained Wallstent was 3.5 +/- 0.3 mm and 3.3 +/- 0.3 mm for the Wiktor stent (P less than 0.05). Both types of stents resulted in a similar increase in minimal luminal diameter immediately following implantation (Wallstent: 2.34 +/- 0.38 mm, Wiktor stent: 2.43 +/- 0.27 mm, NS). Furthermore, there was a similar decrease in diameter stenosis and increase in minimal luminal cross-section area following implantation of both stents. These morphological changes were associated with a normalization of the hemodynamic parameters in both groups. It is concluded that, although the Wallstent and Wiktor stent are different in design and mechanical characteristics, there is a similar immediate improvement in stenosis geometry following implantation of both devices.

1. Four cumulative 10 min intravenous infusions of 0.05, 0.2, 0.5 and 2.0 mg min-1 were used to compare the cardiovascular profile of 5 novel nitrate-esters dissolved in Intralipid 10% to that of nitroglycerin (GTN) in conscious pigs. 2. Infusion of Intralipid 10% alone had no effect on any of the systemic haemodynamic parameters. GTN infusions decreased mean arterial blood pressure dose-dependently from 94 +/- 2 mmHg to 79 +/- 3 mmHg (P less than 0.05) and raised cardiac output from 2.74 +/- 0.09 l min-1 to 3.40 +/- 0.18 l min-1 (P less than 0.05) due to an increase in heart rate (by up to 43 +/- 3%), as stroke volume decreased slightly. Systemic vascular resistance decreased (by 32 +/- 3%) and left ventricular end-diastolic pressure fell from 5.2 +/- 0.4 mmHg to 2.2 +/- 0.5 mmHg (both P less than 0.05). 3. The novel compounds CEDO 8811, CEDO 8834 and CEDO 8901 increased cardiac output only at the highest dose (7%, 8% and 9%, respectively). There was no change in mean arterial blood pressure as the increase in cardiac output was counterbalanced by arterial vasodilatation. All three compounds reduced left ventricular end-diastolic pressure slightly. 4. CEDO 8816 was a more potent arterial and venodilator than the aforementioned CEDO compounds, as the decreases in systemic vascular resistance and left ventricular end-diastolic pressure were already significant at lower doses. The fall in stroke volume was fully compensated by the increase in heart rate and as a result cardiac output increased by 11 +/- 3% (P less than 0.05) at the highest dose. 5. CEDO 8956 was the most potent vasodilator of the novel compounds and exhibited a cardiovascular profile similar to that of GTN. Left ventricular end-diastolic pressure decreased significantly during infusion of 0.2mgmin-'. Mean arterial blood pressure decreased by 11 +/- 2% (P < 0.05) in spite of an increase in cardiac output by up to 20 +/- 2% (P < 0.05), due to a decrease (by 27 +/- 1%, P <0.05) in systemic vascular resistance. The increases in heart rate (20 +/- 5%, P < 0.05) and LVdP/dtmax (38 +/- 4%, P < 0.05) were, however, considerably less after CEDO 8956 than after GTN. 6. The potential of CEDO 8956 in the treatment of chronic left ventricular dysfunction was evaluated during administration to conscious pigs (21-23 kg), in which the left circumflex coronary artery was ligated 4 weeks earlier. In these animals, baseline values for cardiac output and LVdP/dtx were lower and those of systemic vascular resistance and left ventricular end-diastolic pressure were higher than in the first group of experiments. 7. Both GTN and CEDO 8956 in doses of 0.05 to 2.0 mg inm increased cardiac output dosedependently (by up to 34% and 19%, respectively). The decrease in systemic vascular resistance was larger with GTN (35%) than with CEDO 8956 (17%), which resulted in a 13% decrease in mean arterial pressure during infusion of GTN, whereas there was no change in mean arterial pressure during infusion of CEDO 8956. Both compounds increased LVdP/dt,,,,X (by 48% and 30%, respectively) and lowered left ventricular end-diastolic pressure to normal levels. 8. At a dose of 1.0Omg min- 1, both GTN and CEDO 8956 increased left ventricular blood flow parallel to the increase in myocardial oxygen demand. At this dose, GTN also caused vasodilatation in the vascular beds of the brain, kidneys and adrenals. With CEDO 8956 no significant changes were achieved. 9. We conclude that the cardiovascular profile of CEDO 8956 in both normal animals and in animals with chronic left ventricular dysfunction warrants further study on its usefulness in the treatment of a number of cardiovascular disorders.

1. We studied the effects of four doses of nimodipine (0.5, 1, 2 and 4 micrograms kg-1 min-1) on systemic haemodynamics and on regional vascular beds, in particular the cerebral circulation, in conscious pigs. 2. Nimodipine caused dose-dependent, probably reflex-mediated, increases in heart rate (42% with the highest dose) and cardiac output (54%), while arterial blood pressure was only minimally affected. Left ventricular end-diastolic pressure and systemic vascular resistance decreased dose-dependently (35-40% at the highest dose) while stroke volume remained unchanged. 3. Total brain blood flow was not affected by the drug. Furthermore, we could not demonstrate any regional cerebral differences, as blood flows to both cerebral hemispheres as well as the diencephalon, cerebellum and brain stem remained unchanged. 4. Blood flow to the kidneys, liver, small intestine and skin also did not change. Nimodipine caused dose-dependent increases in blood flow to the stomach (95%), myocardium (97%) and adrenal glands (102%), while blood flow to skeletal muscles (267%) increased most. 5. It is concluded that in the conscious pig, nimodipine is an arterial vasodilator which shows some selectivity for the skeletal muscle vasculature but does not increase total or regional cerebral blood flow.

Ligation of the left anterior descending coronary artery in open-chest pigs for 20 min caused a complete loss of regional myocardial function, which did not recover during the first two hours of reperfusion. Infusion of the stable prostacyclin analogue Iloprost (100 ng kg-1 min-1) did not prevent the loss of systolic wall function during ischaemia. Recovery of regional myocardial function during the first two hours of reperfusion was enhanced to 40% of baseline by Iloprost. This effect of Iloprost cannot be explained by a decreased O2-demand during ischaemia or an enhanced recovery of myocardial ATP content.