Technical advance in silico and in vitro development of a new bipolar radiofrequency ablation device for renal denervation.

BACKGROUND: Renal denervation with radiofrequency ablation has become an accepted treatment for drug-resistant hypertension. However, there is a continuing need to develop new catheters for high-accuracy, targeted ablation. We therefore developed a radiofrequency bipolar electrode for controlled, targeted ablation through Joule heating induction between 60 and 100 °C. The bipolar design can easily be assembled into a basket catheter for deployment inside the renal artery. METHODS: Finite element modeling was used to determine the optimum catheter design to deliver a minimum ablation zone of 4 mm (W) × 10 mm (L) × 4 mm (H) within 60 s with a 500 kHz, 60 Vp-p signal, and 3 W maximum. The in silico model was validated with in vitro experiments using a thermochromic phantom tissue prepared with polyacrylamide gel and a thermochromic ink additive that permanently changes from pink to magenta when heated over 60 °C. RESULTS: The in vitro ablation zone closely matched the size and shape of the simulated area. The new electrode design directs the current density towards the artery walls and tissue, reducing unwanted blood temperature increases by focusing energy on the ablation zone. In contrast, the basket catheter design does not block renal flow during renal denervation. CONCLUSIONS: This computational model of radiofrequency ablation can be used to estimate renal artery ablation zones for highly targeted renal denervation in patients with resistant hypertension. Furthermore, this innovative catheter has short ablation times and is one of the lowest power requirements of existing designs to perform the ablation.

Ex vivo and in vivo coronary ostial locations in humans.

PURPOSE: Knowledge of the normal in vivo distribution and variation of coronary ostial locations is essential in the planning of various interventional and surgical procedures. However, all studies to date have reported the distribution of coronary ostia locations only in cadaver hearts. In this study, we sought to assess the distribution of coronary ostial locations in patients using cardiac dual-source computed tomography (CT) and compare these values to those of human cadaveric specimens. METHODS: Measurements of the coronary ostia location were performed in 150 patients undergoing dual-source CT and in 75 cadavers using open measurement techniques. All 150 patients had a normal aortic valve function and no previous cardiac intervention or surgery. The location of the right and left coronary origin in relation to the aortic annulus and the height of the sinus of Valsalva were measured. RESULTS: Mean ostial locations at CT were 17.0 (+/-3.6) mm and 15.3 (+/-3.1) mm for the right and left coronary ostia, with large variations of both sides (right: 10.4-28.5 mm; left: 9.8-29.3 mm). In cadavers, mean locations were 14.9 (+/-4.3) mm [5-24 mm] for right and 16.0 (+/-3.6) mm [9-24 mm] for left coronary ostia. Comparison of CT and cadaver data showed statistically significant differences for right (P < 0.0001) but not left (P = 0.1675) coronary ostia. CONCLUSIONS: This study provides data of normal coronary ostial origins and demonstrates significant differences between in vivo and ex vivo measurements regarding the right coronary ostium. The observed large variations of coronary ostia origins emphasize the importance of considering such anatomic variations in the development of treatments.

Proteinuria and fusion of podocyte foot processes in rats after infusion of cytokine from patients with idiopathic minimal lesion nephrotic syndrome.

BACKGROUND/AIMS: We report on the isolation of a factor secreted by peripheral blood mononuclear cells from patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) in relapse and its effect on proteinuria and podocyte morphology in the rat. METHODS: Peripheral blood mononuclear cells from patients with IMLNS (in relapse and in remission) and patients with focal segmental glomerulosclerosis were cultured for 72 h. Supernatants from 20 x 10(6) cultured cells were separated by liquid chromatography into three fractions according to markers (bovine serum albumin, beta-amylase, and apoferritin). Each supernatant fraction was infused into rats for 5 days using an osmotic pump. Proteinuria, 24-hour albumin excretion or albumin/creatinine ratio in a 24-hour urine collection, was measured daily starting 3 days prior to fraction infusion. Renal tissue was obtained for electron microscopy studies. The beta-amylase fraction underwent electrophoresis using isoelectric focusing gel. RESULTS: When protein excretion was compared prior to and during supernatant fraction infusion, a significant increase in proteinuria was observed only when beta-amylase fraction from IMLNS patients in relapse was infused (p < 0.05). Protein electrophoresis of the beta-amylase fraction showed a single band at pH 6.0 only in samples from IMLNS patients in relapse. The band was composed of two proteins, beta-amylase and a 100-kDa glycoprotein. Fusion of foot processes was observed only when the beta-amylase fraction from IMLNS patients in relapse was infused. CONCLUSIONS: The infusion of the beta-amylase fraction containing a 100-kDa glycoprotein from IMLNS patients in relapse induced proteinuria and effacement of foot processes in the rat. This protein may play a role in the pathogenesis of IMLNS.

A Chlamydia pneumoniae infection model using established human lymphocyte cell lines.

Since current studies indicate possible infection of human lymphocytes with Chlamydia (Chlamydophila) pneumoniae, establishment of an in vitro C. pneumoniae infection model using lymphocyte cell lines was demonstrated. Human lymphoid cell lines (Molt 4 [T-cell] and P3HR1 [B-cell]) were utilized for this purpose besides human monocyte cell line (THP-1) and human epithelial cell line (HEp-2), as a reference of monocyte/macrophage cells and a positive control for support of C. pneumoniae growth, respectively. Both lymphoid cells (Molt 4 and P3HR1) supported the growth of C. pneumoniae as demonstrated by Chlamydia inclusion formation, detection of increased infective progenies and increased bacterial antigen levels. Similar data were obtained using monocyte THP-1 cells. However, the bacterial growth in these cells was less than that in HEp-2 cells. The electron microscopic study showed typical inclusions with many Chlamydia elementary bodies in lymphoid cells tested, similar to that seen in HEp-2 cells. These results indicate that C. pneumoniae can infect cells with lymphocyte properties and this infection model with lymphoid cell line cells could be valuable to study details of lymphocyte-C. pneumoniae interaction.