Background-Early clinical studies demonstrated the feasibility of local paclitaxel delivery in reducing restenosis after treatment of de novo coronary lesions in small patient populations. Methods and Results-We conducted a randomized, double-blind trial of 536 patients at 38 medical centers evaluating slow-release (SR) and moderate-release (MR) formulations of a polymer-based paclitaxel-eluting stent (TAXUS) for revascularization of single, primary lesions in native coronary arteries. Cohort I compared TAXUS-SR with control stents, and Cohort II compared TAXUS-MR with a second control group. The primary end point was 6-month percent in-stent net volume obstruction measured by intravascular ultrasound. Secondary end points were 6-month angiographic restenosis and 6-and 12-month incidence of major adverse cardiac events, a composite of cardiac death, myocardial infarction, and repeat revascularization. At 6 months, percent net volume obstruction within the stent was significantly lower for TAXUS stents (7.9% SR and 7.8% MR) than for respective controls (23.2% and 20.5%; PϽ0.0001 for both). This corresponded with a reduction in angiographic restenosis from 17.9% to 2.3% in the SR cohort (PϽ0.0001) and from 20.2% to 4.7% in the MR cohort (Pϭ0.0002). The incidence of major adverse cardiac events at 12 months was significantly lower (Pϭ0.0192) in the TAXUS-SR (10.9%) and TAXUS-MR (9.9%) groups than in controls (22.0% and 21.4%, respectively), predominantly because of a significant reduction in repeat revascularization of the target lesion in TAXUS-treated patients. Conclusions-Compared

Background-This research describes an early preclinical study of the biophysical mechanisms governing changes in myocardial T 2 during vasodilation in normal myocardium. Methods and Results-Theoretical modeling and experimental studies in an instrumented pig model (nϭ7) provided measures of changes in myocardial T 2 , relative blood volume (BV), and microcirculation oxygen levels (%O 2 ) during intracoronary adenosine infusion. Intracoronary adenosine increases perfusion without increasing blood volume or cardiac metabolic rate; thus, T 2 elevations should reflect elevated microcirculation oxygen levels. Robust strategies were used for magnetic resonance imaging (MRI) data collection. Measures of myocardial and vascular T 1 before and after Clariscan (Amersham Health) injection provided blood volume assessment. Changes in microcirculation oxygen levels were estimated via direct blood sampling from the left anterior descending (LAD) coronary vein. Perfusion changes were monitored using a Doppler flow wire within the left main coronary artery. Myocardial T 2 elevations (⌬T 2 ϭ17Ϯ8%) within the LAD arterial perfusion bed were related to elevations in perfusion (coronary velocity reserveϭ3.2Ϯ0.4) and coronary venous %O 2 [⌬(LAD CV%O 2 ) ϭ56Ϯ11%], whereas blood volume (⌬BVϭ0 Ϯ2%) and cardiac metabolic rate [⌬(heart rate x blood pressure) ϭ Ϫ4Ϯ11%] remained constant. Conclusions-Myocardial T 2 elevation during intracoronary adenosine infusion was significant and repeatable, caused by increases in microcirculation oxygen levels. Changes in microcirculation oxygen levels of approximately 40%O 2 should be detectable by this technique. This sensitivity should suffice for differentiating normal from abnormal myocardium via measurement of myocardial perfusion reserve.