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Background: Coronary stenting is associated with two major complications: subacute thrombosis and neointimal proliferation resulting in restenosis. Our hypothesis is that the biocompatibility of metallic stents can be improved by coating with a polymer membrane that delivers agents that favorably modify the local arterial microenvironment. This study evaluates the kinetics, distribution, and bioactivity of the model drug forskolin delivered to the local arterial wall by a polyurethane-coated removable metallic stent., Methods and Results: Stents were used in rabbit carotid arteries (n = 20) for as long as 24 hours. The quantity of forskolin bound to the stent decreased exponentially with a half-life of 5.8 hours. Blood concentrations peaked at 140 +/- 39 pg/microL at 4 hours. The adjacent arterial media contained 60 +/- 39 ng/mg, which was 380- and 460-fold greater than the contralateral carotid media and the systemic blood, respectively (P < .0001). Media forskolin concentrations declined exponentially over time with a tissue half-life of 5.0 hours. Drug distributed throughout the vessel wall with decreasing gradients in the radial and axial dimensions consistent with a diffusion process. Removal of the stent was associated with a 100-fold decline in media forskolin concentration within 2 hours. Forskolin release was associated with a sustained 92% increase in carotid blood flow and a 60% decrease in local arterial resistance compared with coated control stents (P < .005). In another set of rabbits (n = 14) using a carotid crush injury, flow-reduction model, forskolin prolonged the time to flow variation and occlusion by 12-fold compared with the use of bare metal stents and 5-fold compared with the use of polyurethane-coated stents (P < .0001)., Conclusions: A polymer-coated metallic stent can deliver forskolin to the local arterial wall in high concentrations relative to the blood or other tissues. High local drug concentrations are dependent on maintaining stent-to-tissue gradients. The delivered drug is biologically active, demonstrating vasodilating and antiplatelet properties.

Background: We have developed a new measure of myocardial viability, the water-perfusable tissue index (PTI), which is calculated from transmission, C15O, and H2(15)O positron emission tomography (PET) data sets. It is defined as the proportion of the total anatomical tissue within a given region of interest (ROI) that is capable of rapidly exchanging water and has units g (perfusable tissue)/g (total anatomical tissue). The aim of this study was to assess the prognostic value of PTI in predicting improvement in regional wall motion after successful thrombolysis for acute myocardial infarction (AMI) and to measure the myocardial blood flow to the perfusable tissue (MBFp, ml/min/g [perfusable tissue]). Furthermore, PTI was compared with 18FDG metabolic imaging in patients with old myocardial infarction (OMI)., Methods and Results: PET scans were performed in healthy volunteers (group 1, n = 8), patients with OMI (group 2, n = 15), and in patients who were successfully thrombolysed after an AMI (group 3, n = 11). Systolic wall thickening was measured by two-dimensional echocardiography within 2-4 days of AMI and after 4 months to assess contractile recovery. In the healthy volunteers, MBFp was 0.95 +/- 0.13 ml/min/g (perfusable tissue). PTI in these regions was 1.08 +/- 0.07 g (perfusable tissue)/g (total anatomical tissue), which was consistent with all normal myocardium being perfusable by water. In the OMI group, the ratio of the relative 18FDG activity to the relative MBFp defect (metabolism-flow ratio) was calculated for each asynergic segment. Regions in which the metabolism-flow ratio was greater than or equal to 1.20 were considered reversibly injured, whereas those in which the ratio was less than 1.20 were deemed irreversibly injured. PTI in the former group of regions (n = 9) was 0.75 +/- 0.14 g (perfusable tissue)/g (total anatomical tissue) and was significantly higher than in irreversibly injured regions (n = 6) (0.53 +/- 0.12 g [perfusable tissue]/g [total anatomical tissue], p less than 0.01). Values of MBFp were similar in these segments. Seven of 12 segments in the AMI patients showed improved systolic wall thickening on follow-up. PTI in these recovery segments was 0.88 +/- 0.10 g (perfusable tissue)/g (total anatomical tissue) (p = NS versus control). PTI in the nonrecovery regions was 0.53 +/- 0.11 g (perfusable tissue)/g (total anatomical tissue), which was similar to the segments in group 2 in which 18FDG uptake was absent. MBFp was similar in both the recovery and nonrecovery segments in the subacute phase., Conclusions: These data indicate that PTI may be a good prognostic indicator for the recovery of contractile function after successful thrombolysis and show that myocardial viability may be assessed by PET without metabolic imaging.

Background: Oxygen-15-labeled water is a diffusible, metabolically inert myocardial blood flow tracer with a short half-life (2 minutes) that can be used quantitatively with positron emission tomography (PET). The purpose of this study was to validate a new technique to quantify myocardial blood flow (MBF) in animals and to assess its application in patients., Methods and Results: The technique involves the administration of 15O-labeled carbon dioxide (C15O2) and rapid dynamic scanning. Arterial and myocardial time activity curves were fitted to a single tissue compartment tracer kinetic model to estimate MBF in each myocardial region. Validation studies consisted of 52 simultaneous measurements of MBF with PET and gamma-labeled microspheres in nine closed-chest dogs over a flow range of 0.5-6.1 ml/g/min. A good correlation between the two methods was obtained (y = 0.36 + 1.0x, r = 0.91). Human studies consisted of 11 normal volunteers and eight patients with chronic stable angina and single-vessel disease, before and after intravenous dipyridamole infusion. In the normal group, MBF was homogeneous throughout the left ventricle both at rest and after administration of dipyridamole (0.88 +/- 0.08 ml/g/min and 3.52 +/- 1.12 ml/g/min, respectively; p less than or equal to 0.001). In patients, resting MBF was similar in the distribution of the normal and stenotic arteries (1.03 +/- 0.23 and 0.93 +/- 0.21 ml/g/min, respectively). After dipyridamole infusion, MBF in normally perfused areas increased to 2.86 +/- 0.83 ml/g/min, whereas in the regions supplied by stenotic arteries it increased to only 1.32 +/- 0.27 ml/g/min (p less than or equal to 0.001)., Conclusions: PET with C15O2 inhalation provides an accurate noninvasive quantitative method for measuring regional myocardial blood flow in patients.