Maria L. Aguirre

Cylindrical ultrasonic transducers for cardiac catheter ablation

This study was designed to evaluate the feasibility of using cylindrical ultrasound transducers mounted on a catheter for the ablation of cardiac tissues. In addition, the effects of ultrasound frequency and power was evaluated both using computer simulations and in vitro experiments. Frequencies of 4.5, 6, and 10 MHz were selected based on the simulation studies and manufacturing feasibility. These transducers were mounted on the tip of 7-French catheters and applied in vitro to fresh ventricular canine endocardium, submerged in flowing degassed saline at 37/spl deg/C. When the power was regulated to maintain transducer interface temperature at 90-100/spl deg/C, the 10-, 6-, and 4.5-MHz transducers generated a lesion depth of 5.9/spl plusmn/0.2 mm, 4.6/spl plusmn/1.0 mm, and 5.3/spl plusmn/0.9 mm, respectively. The 10-MHz transducer was chosen for the in vivo tests since the maximum lesion depth was achieved with the lowest power. Two dogs were anesthetized and sonications were performed in both the left and right ventricles. The 10-MHz cylindrical transducers caused an average lesion depth of 6.4/spl plusmn/2.5 mm. In conclusion, the results show that cylindrical ultrasound transducers can be used for cardiac tissue ablation and that they may be able to produce deeper tissue necrosis than other methods currently in use.

Preliminary results using ultrasound energy for ablation of the ventricular myocardium in dogs

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Intimal growth and neovascularization in human stenotic vein grafts

BACKGROUND Myointimal thickening and microvessel ingrowth are commonly observed in vein graft stenosis, which complicates a third of infrainguinal bypass procedures. But a direct correlation between these two features has not been established. Our purpose was to analyze the relationship between neovascularity and intimal thickness in human vein grafts. STUDY DESIGN Twenty-two explant stenotic vein grafts (STVG), 8 nonstenotic arterialized vein grafts (AVG), and 20 age-matched control greater saphenous veins (CGSV) were analyzed histologically and compared morphologically by light microscopy. Digitized computer image analysis was used to measure intimal thickness and quantitate microvessel ingrowth. Immunolocalization of endothelial cells around the lumen and in microvessels was determined using antibodies to factor VIII and to endothelial nitric oxide synthase (eNOS), respectively. RESULTS Focal areas of endothelial disruption and thrombus deposition were present in 23% (5 of 22) of stenotic vein grafts. The neointima of STVG grafts was two- and fourfold thicker than that of AVG and CGSV, respectively (p < 0.0001). Microvessels were most frequently observed in the adventitia and media of STVG and increased in number with increasing intimal thickness (p < 0.001 by ANOVA). CONCLUSIONS A fourfold increased neointimal thickness in critically stenotic vein grafts is associated with increased medial and adventitial neovascularization. Remodeling alone with doubling of the intimal thickness in nonstenotic arterialized vein grafts does not appear to be associated with enhancement of the graft microvasculature. More specific observations using an experimental model may allow us to further define the role of angiogenesis in vein graft stenosis and to determine the therapeutic implications of such observations.

In-vivo tissue uptake and retention of Sn-117m(4+)DTPA in a human subject with metastatic bone pain and in normal mice.

Organ and tissue uptake and retention of Sn-117m(4+)DTPA were studied in a human subject treated for metastatic bone pain, and the results were compared with the biodistribution studies in five normal mice. The explanted organs from a patient who received a therapy dose of 18.6 mCi (688.2 MBq) Sn-117m(4+)DTPA and who died 47 days later were imaged with a gamma-camera, and tissue samples were counted and also autoradiographed. Bone, muscle, liver, fat, lungs, kidneys, spleen, heart and pancreas tissue samples were assayed in a well counter for radioactivity. Regions of interest were drawn over bone and major organs to calculate and quantify clearance times using three in vivo Sn-117m(4+)DTPA whole-body scintigrams acquired at 1, 24 and 168 h after injection. Five normal mice injected with the same batch of Sn-117m(4+)DTPA as used for the human subject were sacrificed at 24 h, and tissue samples were collected and assayed for radioactivity for comparison with the human data. For the human subject, whole-body retention at 47 days postinjection was 81% of the injected dose, and the rest (19%) was excreted in urine. Of the whole-body retained activity at 47 days, 82.4% was in bone, 7.8% in the muscle and 1.5% in the liver, and the rest was distributed among other tissues. Gamma-ray scintigrams and electron autoradiographs of coronal slices of the thoracolumbar vertebral body showed heterogeneous metastatic involvement with normal bone between metastatic lesions. There was nonuniform distribution of radioactivity even within a single vertebral body, indicating normal bone between metastatic lesions. Lesion-to-nonlesion ratios ranged from 3 to 5. However, the osteoid-to-marrow cavity deposition ratio, from the microautoradiographs, was 11:1. The peak uptake in the human bone was seen at 137 h with no biological clearance. Soft tissues showed peak uptake at 1 h and exhibited three compartmental clearance components. Whole-body retention in normal mice was 38.7% of the injected dose at 24 h and the rest was excreted. At 24 h postinjection, bone in mice showed 84.2% of the whole-body retention, muscle 1.7% and liver 1.4%, and the rest was distributed in other soft tissues. Percent distribution of the retained dose among bone, muscle, liver and other soft tissues is very similar between mice and a human subject. To calculate precise radiation absorbed doses from bone pain palliation radionuclides, it is necessary to take into account soft-tissue uptake and retention that may not be readily evident from routine external gamma-scintigraphy.

Lipid peroxidation: A possible factor in late graft failure of coronary artery bypass grafts☆

Atherosclerosis is the paramount cause of late vein graft failure after coronary artery bypass grafting. Lipid peroxidation, which may play a significant role in the initiation and progression of atherosclerosis, was examined in segments of vein grafts (n = 6) harvested at reoperation for coronary disease. These were analyzed for cholesterol, phospholipid, triglyceride, and lipid peroxides. Nonatherosclerotic vascular tissues, including coronary arteries (n = 6), saphenous veins (n = 9), and donor aortic specimens (n = 11) were analyzed for comparison. Risk factors for atherosclerosis including elevated serum cholesterol and triglycerides, smoking, and hypertension were more frequent in patients with coronary artery disease compared to organ donors. Lipid peroxides were elevated in explanted vein grafts when compared to either saphenous vein, coronary artery or donor aorta. Lipid peroxides were not significantly different in saphenous vein when compared to coronary artery, but levels in both of these tissues were greater than in donor aorta. Although increased levels of lipid peroxides in explanted veins may simply reflect morphologic changes in these grafts, the known effects of lipid peroxides on a number of biochemical events suggest that they may contribute directly to graft failure after coronary artery bypass grafting.

Fluorescence response of selected tissues in the canine heart: an attempt to find the conduction system

Fluorescence response of canine heart tissue is studied in an attempt to localize the conduction system atrioventricular (AV) node. Data is collected for 364 nm and 308 nm illumination via a 750 micrometers diameter fiber placed against the tissue. This is done for sample locations in the right atrium, AV ring, and right ventricle, and for a rectilinear grid of sample locations in the AV node region. Sample locations are marked via tissue ablation with a 2.1 micrometers Ho:YAG laser and removed for histological analysis. Fluorescence responses are given for 364 nm and 308 nm illumination. No evidence of distinguishable fluorescence by the AV node is seen at either wavelength.