Echocardiographic imaging of technically difficult patients in the intensive care unit: use of optison in combination with fundamental and harmonic imaging.

Previous studies of intravenous contrast agents have excluded patients in the intensive care unit. These patients remain among the most technically difficult to image with ultrasound. We studied the effect of different imaging modalities with and without intravenous contrast (Optison) on endocardial border visualization during echocardiography. Fifty patients in the intensive care unit (32 men, 24 on mechanical ventilator, 10 with chest bandages; mean age, 59 years; mean weight, 91.7 kg; mean height, 67.6 inches) were considered to have technically difficult images when the endocardium could not be visualized in at least 2 of the 6 segments in either apical view. Each patient was studied with the use of fundamental (F), harmonic (H), fundamental + Optison (F + O), and H + O techniques, with standard long-axis, short-axis, and apical 4- and 2-chamber views. Intravenous Optison (0.5 to 1.5 mL) was given before F + O and H + O imaging. There were no contrast-related side effects noted. All images were stored digitally in a quad-screen format. For each set of images, segments (n = 22) were given an endocardial border visualization score of 0 if not visualized, 1 if visualized in either systole or diastole, and 2 if visualized in both. There was stepwise improvement in endocardial border visualization, with mean endocardial border visualization score of 1.09 +/- 0.83 (F), 1.33 +/- 0.81 (H), 1.64 +/- 0.62 (F + O), and 1.90 +/- 0.35 (H + O). There was a statistically significant difference between each group (P <.001). The incremental benefit of Optison was greater with harmonic imaging than with fundamental (P <.001). The use of Optison is safe and effective in the intensive care unit. In combination with harmonic imaging, contrast provides maximal endocardial border delineation during echocardiographic imaging of technically difficult patients in the intensive care unit.

Treatment of vascular thrombosis with enoxaparin in orthotopic heart transplant patients during the early postoperative period.

Management of anti-coagulation in the early period after orthotopic heart transplantation, when the frequency of invasive procedures to assess for graft rejection is high, presents a difficult clinical problem in which the need for effective therapy must be weighed against the desire for outpatient treatment. In this report, we summarize the clinical course and long-term outcome of 6 patients from our center in whom vascular thrombosis was treated on an outpatient basis with enoxaparin. We conclude that the use of enoxaparin may provide a safe and reasonable alternative to conventional anti-coagulation therapy during this period.

Detection of subclinical coronary atherosclerosis using two-dimensional, high-resolution transthoracic echocardiography.

OBJECTIVES: We evaluated whether two-dimensional high-resolution transthoracic echocardiography (HR-2DTTE) can detect changes in arterial wall thickness and size associated with subclinical coronary artery disease (CAD). BACKGROUND: Arterial wall thickening, compensatory arterial enlargement and a preserved arterial lumen characterize subclinical atherosclerosis. Detection of these changes during the asymptomatic stage of CAD may allow early treatment and prevention of acute coronary events. METHODS: Twenty-six patients with angiographically proven CAD and 29 normal volunteers underwent HR-2DTTE evaluation of the left anterior descending coronary artery (LAD) using an ATL 5000 echograph (Advanced Technology Laboratories, Bothell, Washington) with a 4 to 7 MHz transducer. Significant (>70%) LAD stenosis was present in 15 patients (mean 82%); 11 patients did not have significant LAD stenosis (mean 26%) and represented a surrogate for subclinical LAD disease. Wall thickness, maximal luminal diameter and external diameter of the LAD were measured. RESULTS: Left anterior descending coronary artery wall thickness was larger in patients (1.9 +/- 0.4 mm) than it was in volunteers (0.9 +/- 0.1 mm, p < 0.001). The external diameter of the LAD was (6.0 +/- 1.1 mm) in patients and (3.9 +/- 0.7 mm) in volunteers (p < 0.001). Luminal diameter was 2.2 +/- 0.5 mm in patients and 2.1 +/- 0.6 mm in volunteers (p = NS). There was no difference in wall thickness (1.9 +/- 0.4 mm vs. 2.0 +/- 0.4 mm), luminal diameter (2.2 +/- 0.5 mm vs. 2.2 +/- 0.4 mm) and external diameter (5.9 +/- 1.0 mm vs. 6.2 +/- 1.2 mm) between the patients with <70% and >70% LAD stenosis. CONCLUSIONS: Left anterior descending coronary artery wall thickness and external diameter are significantly increased in patients with CAD as compared with normal subjects, and HR-2DTTE is sensitive enough to detect these differences. Wall thickness and external diameter are increased to the same extent in patients with obstructive and subclinical LAD disease.

Effect of atherosclerosis on transmural convection an arterial ultrastructure. Implications for local intravascular drug delivery.

Local infusion of agents through perforated catheters may reduce neointimal formation following vascular angioplasty. Such treatment will succeed only if the drug is retained within the arterial intima long enough to promote repair. Drugs will be dispersed throughout the wall predominantly by transmural convection instead of diffusion if the Peclet number, Pe = J (1-delta f)/P, is greater than unity, where J is the transmural fluid flow per unit surface area and delta(f) and P are the reflection and permeability coefficients to the drug, respectively. Although the targets of local drug delivery will be atherosclerotic vessels, little is known about the transport properties of these vessels. Accordingly, we evaluated the effects of hypercholesterolemia and atherosclerosis on J per unit pressure (hydraulic conductance, Lp) and on ultrastructure in femoral arteries. Measurements were made at 30, 60, and 90 mm Hg in anesthetized New Zealand white rabbits fed a normal diet (n = 6) and after 3 weeks of lipid feeding (n = 19). Atherosclerosis was induced in six lipid-fed animals by air desiccation of a femoral artery. Hydraulic conductance was significantly greater in vessels from hypercholesterolemic than from normal animals and decreased with pressure only in hypercholesterolemic arteries. Atherosclerosis did not augment hydraulic conductance compared with hypercholesterolemia alone. Electron microscopic examination demonstrated damaged endothelium in hypercholesterolemic arteries and both altered endothelium and less tightly packed medial tissue, compared with controls, in atherosclerotic vessels, at least at lower pressures. Peclet numbers for macromolecules exceeded unity for all three groups of arteries and reached 0.3 to 0.4 for molecules as small as heparin. Thus, convection plays a dominant role in the distribution of macromolecular agents following local delivery and may result in their rapid transport to the adventitia in the femoral artery.

Vascular repair mechanisms after directional atherectomy or percutaneous transluminal coronary angioplasty in atherosclerotic rabbit iliac arteries.

Although directional atherectomy (DA) reduces the plaque burden, successful revascularization is not associated with a reduced restenosis rate when compared with percutaneous transluminal coronary angioplasty (PTCA). The purpose of this study was to compare and contrast the vascular response to DA-induced and PTCA-induced injury. Six to 8 weeks after induction of atherosclerosis, PTCA (n = 34) was performed in one iliac artery and DA in the other (n = 30). Arteries were obtained at 6 time points: 1, 3, 5, 7, 14, and 28 days. Eleven arteries that did not undergo an intervention acted as controls. Radiograms obtained before and after intervention and at euthanization were compared. Morphometric, histologic, and immunohistochemical analyses were performed. Both PTCA and DA resulted in an immediate increase in luminal diameter that subsequently decreased over the ensuing month. PTCA caused deep dissection (7 of 8 arteries), often extending to the adventitia, whereas stand alone DA resulted in deep cleft formation (4 of 5). Of the 30 arteries that underwent DA, 4 exhibited an increase in luminal diameter in the absence of tissue retrieval. Thrombus was observed in both the dissection planes and the clefts within the first 7 days, and cellular ingrowth was appreciated at 5 to 7 days. By 7 days the artery was repaired, and the histologic appearance of the arteries that had undergone PTCA could not be differentiated from the arteries that had undergone DA. Increased intimal and medial collagen and elastin was noted at 14 and 28 days. An increase in the area bordered by the external elastic lamina was observed in both groups. Although successful DA results in tissue removal and the production of a deep tissue cleft and PTCA causes a dissection, both produce a condition in which the arterial injury exposes the arterial media to blood, causing thrombus formation and inflammation with subsequent cellular accumulation into the thrombotic framework.

Local delivery of biodegradable microparticles containing colchicine or a colchicine analogue: effects on restenosis and implications for catheter-based drug delivery.

OBJECTIVES: This study sought to evaluate the delivery efficiency, intramural retention and antirestenotic efficacy of soluble colchicine or colchicine analogue delivered into the arterial wall after angioplasty as well as the efficacy of these medications after prolonged local release from biodegradable microparticles. BACKGROUND: Local delivery of pharmacologic agents is a potential treatment for restenosis. However, the delivery efficiency of the technique and the choice of agent to modulate cellular proliferation are unknown. It was hypothesized that restenosis would be unaffected by colchicine or a hydrophobic colchicine analogue with short intramural retention, whereas it would be reduced after prolonged local release. METHODS: Rabbit atherosclerotic femoral arteries underwent angioplasty followed by local delivery. Delivery efficiency and intramural retention of 3H-colchicine were evaluated. The effect of agents in soluble formulation or released from microparticles on angiographic and morphometric restenosis was evaluated at 2 weeks and compared with that in the control groups (angioplasty only and local infusion of carrier solution). RESULTS: Delivery of efficiency was 0.01% and intramural retention < 24 h. Neither soluble colchicine formulation reduced restenosis. Microparticles releasing the colchicine analogue reduced restenosis compared with control and colchicine microparticles but not angioplasty alone (p = 0.002). Delivery outside the artery was observed, and the long-term release of both colchicine resulted in toxicity to the adjacent musculature. CONCLUSIONS: Colchicine or the colchicine analogue did not reduce restenosis, although the long-term local release of the colchicine analogue reduced neointimal proliferation resulting from local delivery. Local delivery of cytotoxic agents with insufficient vascular specificity may be limited by toxicity to adjacent tissues resulting from a larger than expected delivery area and prolonged agent retention.

Vascular injury, repair, and restenosis after percutaneous transluminal angioplasty in the atherosclerotic rabbit.

BACKGROUND: Several nonatherosclerotic animal models of restenosis exist and are used for the evaluation of the vascular response to angioplasty-induced injury. However, few studies have evaluated the response of an atherosclerotic vessel to angioplasty. The present study examined the radiographic, histological, immunohistochemical, and morphometric responses over time of atherosclerotic rabbit femoral arteries after percutaneous transluminal angioplasty (PTA). METHODS AND RESULTS: Rabbits (n = 94) underwent arterial dissection and were fed a hypercholesterolemic diet for 3 weeks, and then PTA was performed. Arteries were obtained before PTA and 1, 3, 5, 7, 14, and 28 days after PTA. PTA caused radial stretching of the artery, medial compression, intramural hemorrhage, injury to normal arterial segments, and dissection within the intima and media. Thrombus filled and cellular accumulation repaired the dissection. Peak smooth muscle cell and macrophage DNA synthesis was noted at 3 to 5 days after angioplasty, generally at the dissection but also in normal sections of the artery. Adventitial injury and subsequent adventitial cellular proliferation and collagen production were observed. A rapid decrease in the radiographic minimal luminal diameter was noted at 3 days, resulting from vascular recoil or thrombus filling the dissection. At 7 to 14 days, only 24% to 33% of the luminal loss was accounted for by an increase in the intimal area, and 22% to 28% of the intima was neointima. CONCLUSIONS: Restenosis in an atherosclerotic artery results from a variable combination of intimal proliferation, vascular remodeling/wound contraction, and recoil of the normal section of the artery. The variability of an atherosclerotic artery to PTA injury results from variable dissection, thrombus formation, and cellular response to injury as well as variable scar contraction and elastic recoil.

Regional and arterial localization of radioactive microparticles after local delivery by unsupported or supported porous balloon catheters.

Catheter-mediated intramural delivery of pharmaceutical agents after angioplasty is a potential method to reduce postangioplasty restenosis. The efficacy of such delivery has been limited both by an incomplete initial intramural deposition of delivered agents and by rapid diffusion of soluble agents from the site of delivery. The local delivery of microparticulate agents results in prolonged retention of material at the delivery site. Accordingly this study was designed to evaluate the complementary issue of the initial delivery efficiency and pattern of localization of microparticles after local catheter-mediated delivery with two types of porous balloons. These two types were a "standard" porous balloon (PB) in which hydraulic pressure both inflated the balloon and infused the agents and a porous balloon with a mechanical undergirding that permitted mechanical expansion (PB/ME) before agent infusion. Radioactive cerium 141-labeled microparticles (11.4 microns diameter) were locally delivered into atherosclerotic rabbit femoral arteries after angioplasty to test the hypothesis that use of the PB/ME apparatus would yield enhanced intramural particle deposition and decreased systemic administration by increased balloon-wall contact before microparticle infusion. Six animals underwent infusion with the PB catheter, and seven animals underwent infusion with the PB/ME catheter. An image of the in vivo particle distribution was obtained with a gamma camera during infusion, immediately after infusion, and 1, 3, and 7 days after infusion. Tissue samples from the artery, periadventitia, thigh, calf, and foot musculature, and liver were obtained at animal death, and retained radioactivity was measured with a well counter.(ABSTRACT TRUNCATED AT 250 WORDS)

Methods and devices for local drug delivery in coronary and peripheral arteries.

New developments in catheter design, molecular biology, and polymer chemistry have made it possible to deliver pharmaceutical agents and genetic material directly into the arterial wall to modulate the response to injury. Several local drug delivery catheters of various designs in addition to biodegradable and coated stents are currently being evaluated as devices to facilitate local delivery of agents into the arterial wall. Approaches to locally sustained delivery include the controlled release of medications, the affinity-based delivery of medications administered systemically but accumulated locally, and gene therapy.