Search

Aims: The blood pressure-lowering effect of percutaneous renal denervation (RDN) is controversial. The success of RDN may be device-dependent. We sought to compare the efficacy of RDN by chemical neurolysis using alcohol (Peregrine System Infusion Catheter; Ablative Solutions, Inc., Menlo Park, CA, USA) to RDN by radiofrequency (RF) ablation with the single-electrode RF catheter (Symplicity Flex; Medtronic, Minneapolis, MN, USA) in a porcine model., Methods and Results: This was a prospective, randomised, blinded study. Pigs were assigned to undergo bilateral RF ablation or chemical neurolysis. Primary endpoints were ablation depth and renal tissue norepinephrine (NE) concentrations at three-month follow-up. Twelve pigs underwent RF ablation (n=4) or chemical neurolysis by infusion of 0.3 mL (n=4) or 0.6 mL (n=4) alcohol. Ninety days after RF ablation and chemical neurolysis with 0.3 mL and 0.6 mL of alcohol, mean maximal tissue injury depth was 3.9±1.2 mm, 6.6±1.7 mm and 8.2±2.2 mm, respectively (p<0.001 for either dose of alcohol vs. RF ablation). Compared with historical controls, median renal tissue NE concentration reductions were 66%, 78% and 83% after RF ablation and chemical neurolysis using 0.3 mL and 0.6 mL alcohol, respectively (p=0.107 for chemical neurolysis vs. RF ablation). Mean total ablation area was significantly greater in both (0.3 mL and 0.6 mL) alcohol groups (p=0.0001 for both) than the RF ablation group (30.8±13.7 mm2, 41.6±12.4 mm2 and 11.0±7.5 mm2, respectively)., Conclusions: RDN is more effective using chemical neurolysis than single-electrode RF ablation. Our findings suggest that the efficacy of RDN may be device-dependent.

An intravascular catheter was developed to identify inflammation in coronary atheroma. Inflammation in atheroma is associated with large numbers of macrophages. These cells have increased metabolism, increased expression of chemotactic receptors, and a high frequency of apoptosis-associated phosphatidylserine expression. Each of these parameters can be identified in vivo using specific radiolabeled agents: metabolism can be identified with 18F fluorodeoxyglucose (FDG), receptor expression with 99mTc monocyte chemotactic peptide-1, and apoptosis with 99mTc annexin V. The locally increased concentration of these tracers is readily demonstrable in experimental lesions by ex vivo autoradiography; however, the small lesion size makes it difficult to identify atheroma in the coronaries with conventional imaging equipment. In contrast, with a radiation-sensitive catheter, optimized to sense charged particle rather than gamma or x-radiation, specific lesions could be identified and localized. Charged particle radiation is emitted as a byproduct of nearly all radioactive decay but is typically most abundant in radionuclides that decay by beta emission (either positrons or negatrons). Prototype catheters, using a plastic scintillator mated to an optical fiber, have been tested in the laboratory with the positron-emitting radiopharmaceutical 18FDG. The catheter had sufficient sensitivity to detect lesions concentrating nanocurie concentrations of 18FDG. Ex vivo experiments in apo-e-/- mice confirmed the ability of the catheter to detect 18FDG in aortic lesions. These feasibility studies demonstrate the sensitivity of a beta-sensitive catheter system. Additional mechanical refinements are needed to optimize the system in anticipation of in vivo animal studies.

Purpose: Coronary angiography defines geometry of lumen of artery. However, perhaps 70% of heart attacks occur when minimally obstructive thin capped fibroatheroma rupture, causing thrombus and arterial occlusion. We have developed an intravascular imaging detector to identify vulnerable coronary artery plaque., Procedure: Detector measures beta or conversion electron emissions from plaque-binding radiotracers. Detector assembly fits into a 2-mm diameter catheter and overcomes technical constraints of size, sensitivity, and conformance to intravascular environment., Results: Device was tested by stepping test point sources past detector to verify function. System resolution is 6.7 mm and sensitivity is 400 cps/microCi one mm from detector., Conclusion: This prototype is a first step in imaging of labeled vulnerable plaque in coronary arteries. This type of system may assist in development of targeted and cost effective therapies to lower incidence of acute coronary artery diseases (CAD) such as unstable angina, acute myocardial infarction, and sudden cardiac death.

In buffer systems, heparin and low molecular weight heparin (LMWH) directly inhibit the intrinsic factor X-activating complex (intrinsic tenase) but have no effect on the prothrombin-activating complex (prothrombinase). Although chemical modification of LMWH, to lower its affinity for antithrombin (LA-LMWH) has no effect on its ability to inhibit intrinsic tenase, N-desulfation of LMWH reduces its activity 12-fold. To further explore the role of sulfation, hypersulfated LA-LMWH was synthesized (sLA-LMWH). sLA-LMWH is not only a 32-fold more potent inhibitor of intrinsic tenase than LA-LMWH; it also acquires prothrombinase inhibitory activity. A direct correlation between the extent of sulfation of LA-LMWH and its inhibitory activity against intrinsic tenase and prothrombinase is observed. In plasma-based assays of tenase and prothrombinase, sLA-LMWH produces similar prolongation of clotting times in plasma depleted of antithrombin and/or heparin cofactor II as it does in control plasma. In contrast, heparin has no effect in antithrombin-depleted plasma. When the effect of sLA-LMWH on various components of tenase and prothrombinase was examined, its inhibitory activity was found to be cofactor-dependent (factors Va and VIIIa) and phospholipid-independent. These studies reveal that sLA-LMWH acts as a potent antithrombin-independent inhibitor of coagulation by attenuating intrinsic tenase and prothrombinase.

The Threshold system provides for rapid quantitation of a variety of analytes at sub-femtomole levels, which is fewer than 6 x 10(8) molecules. The operating principles of the measurement system will be described, including the means for chemical modulation of the signal and the subsequent signal detection utilizing a proprietary silicon sensor. The Immuno-Ligand Assay is a universal ligand-binding assay system which provides quantitative measurement of proteins (including antibodies) in a variety of biological media. Assay performance will be described, along with data demonstrating sensitivity, precision and accuracy, for a variety of analytes of interest to the biopharmaceutical industry.

An optical fiber probe is used to both excite and collect fluorescence from a suspension of cells. The configuration of the probe is such that one or a few cells are sensed at a time, with a convenient cell concentration. With fluorescently labeled antibodies to cellular antigens, the fiber optic cytometer is able to identify the presence of a specific set of cells with high sensitivity.

The very potent opioid peptide, dynorphin, has recently been shown by radioimmunoassay and immunocytochemical techniques to be selectively concentrated in the pars nervosa of pituitary, suggesting a possible association of dynorphin with the neurohypophyseal hormones, vasopressin and oxytocin. In this study, we report that pituitary and brain contents of immunoreactive dynorphin in homozygote Brattleboro rats (unable to synthesize vasopressin) are similar to those in heterozygote animals and in normal Long-Evans rats. Thus, the syntheses of immunoreactive dynorphin and vasopressin in the hypothalamo-hypophyseal tract appear to be independently regulated.