These data indicate that coronary artery injury in swine with either balloon inflation or stenting leads to intimal smooth muscle cell proliferation similar to that seen in human restenosis. The degree of intimal proliferation appears to be greater after stenting than after balloon injury. Intracoronary stenting in swine is associated with a marked inflammatory reaction around the stent wires. These models may be helpful in planning systemic and local antirestenosis strategies.

A direct coronary stenting technique using drug-eluting stents may decrease drug-eluting stent efficacy due to possible damage to the surface coating of the stent. The DIRECT is a multicenter, prospective, nonrandomized trial designed to evaluate the direct stenting strategy for the sirolimus-eluting Bx-Velocity stent compared with the historical control (SIRIUS trial, stenting with predilation). Volumetric and cross-sectional intravascular ultrasound analyses at 8-month follow-up were performed in 115 patients (DIRECT n= 64, control n = 51). Patient and lesion characteristics were comparable between groups. The DIRECT group achieved an equivalent uniform expansion index, defined as minimum stent area/maximum stent area x 100, compared with the control group (65.9 +/- 11.7 vs 63.1 +/- 12.7, p = NS). At 8-month follow-up, vessel, stent, lumen, and neointimal volume index (volume in cubic millimeters/length in millimeters) and percent neointimal volume were similar between the DIRECT and control groups (vessel volume index 13.9 +/- 4.40 vs 15.0 +/- 3.83; stent volume index 6.83 +/- 2.02 vs 6.94 +/- 2.04; lumen volume index 6.71 +/- 2.04 vs 6.81 +/- 2.07; neointimal volume index 0.14 +/- 0.24 vs 0.16 +/- 0.23; percent neointimal volume 3.73 +/- 6.97 vs 3.14 +/- 5.32, p = NS for all). In addition, in-stent neointimal hyperplasia distribution was significantly smaller near the distal stent edge (0.22 vs 0.098 mm(3)/mm, p = 0.01 for an average neointimal volume index within 3 mm from the distal stent edge). In conclusion, direct coronary stenting with the sirolimus-eluting Bx-Velocity stent is equally effective in terms of uniform stent expansion and long-term quantitative intravascular ultrasound results compared with conventional stenting using predilation. This strategy appears to be associated with less neointimal hyperplasia near the distal stent edge.

Summary:Restenosis is the most important problem limiting the success of coronary angioplasty. Clinically, restenosis is seen in approximately one-third of patients undergoing percutaneous transluminal coronary angioplasty. Several clinical and angiographic risk factors have been identified which may contribute to the development of restenosis. Histopathologic studies indicate that restenosis is characterized by intimal proliferation of smooth muscle cells in a loose connective tissue matrix. These intimal lesions are associated predominantly with the nonatheromatous portion of the vessel wall. Thinning of the media of the plaque-free wall and marked fragmentation of the internal elustic lamina are also seen. Traumatic injury of the vessel wall during angioplasty probably triggers a series of cellular und subcellular events which may ultimately lead to niyointimal proliferation and restenosis. Although the exact mechanism by which this occurs is unknown, several factors may enhance smooth muscle cell growth and therefore may play a role in the development of restenosis. These include platelet deposition, mechanical stretching of the medi,a, inflammation of the vessel wall, the activity of growth factors, and alterations in vessel geometry. These possible mechanisms of restenosis suggest several potential ways to limit the proliferative response to vascular injury.Anticoagulants and platelet antagonists, direct inhibitors of smooth inuscle proliferation, anti-inflammatory agents, growth factor inhibitors, and new devices which improve final vessel geometry are currently being tested as methods to curb restenosis. Unfortunately, no treatment has yet been shown to reduce significantly the rate of restenosis following angioplasty. The problem of restenosis will most likely be solved by better understanding of the basic molecular and biologic phenomena involved in vascular injury and repair.

Because myocardial reperfusion injury may be caused by various blood constituents, a transient period of blood-free reperfusion was evaluated in closed chest dogs subjected to a 90 min angioplasty balloon occlusion of the left anterior descending coronary artery. In the treated group (n = 13), the balloon remained inflated for an additional 15 min while the infarct vessel was perfused with an acellular oxygenated perfluorochemical emulsion (Fluosol). The balloon was then deflated, permitting blood reperfusion. In the control group (n = 13), the balloon was deflated after 90 min of coronary occlusion. One week after infarction, the area at risk was defined in vivo by monastral blue dye staining, and the area of myocardial necrosis was assessed using triphenyltetrazolium chloride staining with histologic confirmation. Major determinants of infarct size, including rate-pressure product, area at risk and severity of myocardial ischemia (assessed by the extent of ST segment elevation during coronary occlusion), were not significantly different in the two groups. Treated dogs demonstrated a 47% reduction in infarct size expressed as a percent of the area at risk compared with control dogs (27.0 +/- 4.4% versus 50.8 +/- 4.4%, p less than 0.01). Treated dogs also demonstrated a superior global left ventricular ejection fraction (57.5 +/- 2.5% versus 51.0 +/- 2.2%, p less than 0.05) and anterolateral (regional) ejection fraction (32.6 +/- 3.6% versus 19.8 +/- 3.9%, p less than 0.05) compared with values in control dogs assessed by contrast ventriculography after 1 week of reperfusion. It is concluded that a transient period of blood-free reperfusion with an oxygenated perfluorochemical reduces reperfusion injury in a canine model of myocardial infarction.