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Background— The mechanisms of thrombosis on plaque erosion are poorly understood. We examined the potential role of endothelial apoptosis in endothelial erosion and vessel thrombosis. Methods and Results— Segments of New Zealand White rabbit femoral arteries were temporarily isolated in vivo. One artery was incubated with staurosporin for 30 minutes, whereas the contralateral artery was incubated with saline and served as control. Three days later, thrombosis was evaluated angiographically and histologically. TUNEL score in the endothelial layer was significantly increased in staurosporin-treated arteries compared with controls (2.43±0.30 versus 0.93±0.44, respectively; P =0.001). Large areas of endothelial denudation were detectable in staurosporin-treated vessels, whereas endothelium integrity was almost preserved in the saline group. Vessel thrombosis occurred in 58% of staurosporin-treated arteries (7 of 12) but in only 8% of saline-treated segments ( P P =0.04). These results were confirmed in balloon-injured atheromatous arteries. Conclusions— In vivo induction of endothelial apoptosis leads to both vessel thrombosis and endothelial denudation. Endothelial apoptosis may be a critical step in the transition from a stable endothelialized plaque to plaque erosion and thrombosis.

Background— Incomplete ST-segment resolution (STR) after successful primary angioplasty for acute myocardial infarction (AMI) is associated with a poor prognosis. We used intracoronary Doppler velocimetry to investigate whether incomplete STR after primary angioplasty is a marker of severe microcirculatory dysfunction. Methods and Results— Fifty patients with ≤12-hour AMI underwent successful primary angioplasty and systematic stenting with a Doppler guidewire. Patients with incomplete (P =0.007) and lower coronary flow velocity reserve (CVR, 1.3 versus 1.6, P P =0.001) and regional (16% versus 20%, P =0.03) left ventricular ejection fractions and 201 Tl rest-redistribution scintigraphy indicated a larger infarct size (34% versus 16% 201 Tl defect, P =0.007) in patients with Conclusions— After successful primary angioplasty with systematic stenting

Background —Constrictive remodeling plays a prominent role in restenosis after balloon angioplasty, but its regulation remains unclear. Because endothelial dysfunction and changes in extracellular matrix have been reported after angioplasty, this study was designed to simultaneously evaluate endothelial function and collagen and elastin changes after restenosis and arterial remodeling. Methods and Results —Atherosclerosis was induced in femoral arteries of 22 New Zealand White rabbits by air-desiccation and a high-cholesterol diet. One month later, angioplasty was performed. Histomorphometry and in vitro assessment of endothelial function were performed 4 weeks after angioplasty. Restenosis correlated with constrictive remodeling ( r =0.60, P =0.01) but not with neointimal growth ( r =−0.06, P =0.79). Restenosis correlated with an impaired relaxation to acetylcholine (ACh; r =0.61, P =0.02) but not with the response to the endothelium-independent vasodilator sodium nitroprusside ( r =−0.25, P =0.40). Restenosis correlated positively with collagen accumulation ( r =0.69, P =0.004) and inversely with elastin density ( r =−0.48, P =0.05). Relaxations to ACh were significantly more decreased in arteries with constrictive remodeling than in those with enlargement remodeling (3.7±7.9% versus 35.5±15.0%, P =0.04). Neointimal collagen density was significantly higher in arteries with constrictive remodeling than in those with enlargement remodeling (34.5±4.5% versus 18.2±4.7%, P =0.03). Endothelial function and collagen and elastin density were independent predictors of restenosis in the study. Conclusions —These results demonstrate that the severity of restenosis after angioplasty correlated with both defective endothelium-dependent relaxation and increased collagen density.

On October 5 and 6, 2001, less than a month after the terrorist attacks on the United States, a conference on the Pathophysiology, Detection, and Treatment of Vulnerable Plaque was held in Boston, Mass. Nineteen scientists from around the world came together, despite the uncertainty of air travel, to continue the work against this important cause of cardiovascular disease. After the faculty dinner, Dr James Muller, Co-Director of the Vulnerable Plaque Program of the Center for the Integration of Medicine and Innovative Technology (CIMIT) and Director of Clinical Research in Cardiology at the Massachusetts General Hospital and Harvard Medical School, offered the following thoughts on cardiovascular research and the September 11, 2001, terrorist attacks. Dr Muller was one of the co-founders of International Physicians for Prevention of Nuclear War, the organization awarded the 1985 Nobel Peace Prize. The terrible violence of September 11, a day of mass murder of innocent civilians, had many consequences, some of which directly affected our collective effort to prevent death from vulnerable plaque. Specifically, I refer to the irony that September 11 started as a day to celebrate progress for the vulnerable plaque research community. Over 10 000 individuals congregated at the Transcatheter Cardiovascular Therapeutics (TCT) Conference in Washington, DC. The program included a town meeting on vulnerable plaque, one of those wonderful occasions when the scientists working in isolation come together to share progress and ideas. The event was a rare moment when one could actually feel a massive human problem slowly giving way to organized, dedicated human effort. At 8:00 AM, I gave the opening lecture, which included an overview of the topic of vulnerable and invulnerable plaques. At 8:45, while Dr Peter Fitzgerald described the use of ultrasound and OCT for the diagnosis and treatment …

BACKGROUND The presence of persistent myocardial uptake of 18F-deoxyglucose (FDG) within hypoperfused, dysfunctional segments has been shown to predict the recovery of regional contractile function after revascularization. The spectrum of metabolic responses of such hibernating tissue to revascularization is less clear. METHODS AND RESULTS Sixteen patients with previous infarction were studied before and after revascularization by myocardial perfusion imaging using 82Rb positron emission tomography, digitized two-dimensional echocardiography, and imaging of postexercise FDG uptake. Hibernation was identified in 35 of 85 segments showing perfusion and wall motion disturbances before intervention. At follow-up (4.9 +/- 2.6 months after revascularization), hibernating segments were characterized by reduction of wall motion score (p less than 0.001), improvement of perfusion (p less than 0.001), and reduction of FDG activity (p less than 0.001). Of the 35 hibernating segments, however, 10 still had abnormal elevation of FDG uptake (greater than 2 SD above normal) without differing from other hibernating segments with respect to postoperative perfusion or wall motion score. Segments with persistently abnormal metabolism were characterized before intervention by more severe malperfusion (p less than 0.01) and greater FDG activity (p less than 0.01). CONCLUSIONS Although wall motion and perfusion improve with revascularization of hibernating tissue, myocardial metabolism remains abnormal in a significant proportion of segments. These segments are characterized by more extensive perfusion and metabolic changes before revascularization.