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Radiofrequency renal denervation (RDN) is under investigation for treatment of hypertension with variable success. We developed preclinical models to examine the dependence of ablation biomarkers on RDN treatment parameters and anatomical variables. 129 porcine renal arteries were denervated with an irrigated RF catheter with multiple helically arrayed electrodes. Nerve effects and ablation geometries at 7d were characterized histomorphometrically and correlated with associated renal norepinephrine (NEPI) levels. NEPI exhibited a threshold dependence on the percentage of affected nerves (%AN) across the range of treatment durations (30–60sec) and power set-points (6–20W). For 15W/30sec treatments, NEPI reduction and %AN tracked with number of electrode treatments, confirming additive effects of helically staggered ablations. Threshold effects were only attained when ≥four electrodes were powered. Histomorphometry and computational modeling both illustrated that RF treatments directed at large neighboring veins resulted in sub-average ablation areas, and therefore contributed suboptimally to efficacy. Account for measured nerve distribution patterns and the annular geometry of the artery revealed that, regardless of treatment variables, total ablation area and circumferential coverage were the prime determinants of RDN efficacy, with increased efficacy at smaller diameters. SUMMARY: Large animal experiments supported by computational and statistical models that account for arterial microanatomy and nerve distribution explain the dependence of RDN efficacy on procedural parameters, e.g. number of electrode treatments, and anatomic parameters, e.g. arterial diameter and the proximity of veins to ablation sites.

Bone healing, biocompatibility, and safety employing the IlluminOss System (IS), comprised of an inflatable balloon filled with photopolymerizable liquid monomer, was evaluated in New Zealand white rabbits. Successful bone healing and callus remodeling over 6 months was demonstrated radiologically and histologically with IS implants in fenestrated femoral cortices. Biocompatibility was demonstrated with IS implants in brushed, flushed femoral intramedullary spaces, eliciting no adverse, local, or systemic responses and with similar biocompatibility to K-wires in contralateral femurs up to 1 year post-implant. Lastly simulated clinical failures demonstrated the safety of IS implants up to 1 year in the presence of liquid or polymerized polymer within the intramedullary space. Polymerized material displayed cortical bone and vasculature effects comparable to mechanical disruption of the endosteum. In the clinically unlikely scenario with no remediation or polymerization, a high dose monomer injection resulted in marked necrosis of cortical bone, as well as associated vasculature, endosteum, and bone marrow. Overall, when polymerized and hardened within bone intramedullary spaces, this light curable monomer system may provide a safe and effective method for fracture stabilization. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2181-2190, 2017.

Percutaneous intramedullary fixation may provide an ideal method for stabilization of bone fractures, while avoiding the need for large tissue dissections. Tibiae in 18 sheep were treated with an intramedullary photodynamic bone stabilization system (PBSS) that comprised a polyethylene terephthalate (Dacron) balloon filled with a monomer, cured with visible light in situ, and then harvested at 30, 90, or 180 days. In additional 40 sheep, a midshaft tibial osteotomy was performed and stabilized with external fixators or external fixators combined with the PBSS and evaluated at 8, 12, and 26 weeks. Healing and biocompatibility were evaluated by radiographic analysis, micro-computed tomography, and histopathology. In nonfractured sheep tibiae, PBSS implants conformably filled the medullary canal, while active cortical bone remodeling and apposition of new periosteal and/or endosteal bone was observed with no significant macroscopic or microscopic observations. Fractured sheep tibiae exhibited increased bone formation inside the osteotomy gap, with no significant difference when fixation was augmented by PBSS implants. Periosteal callus size gradually decreased over time and was similar in both treatment groups. No inhibition of endosteal bone remodeling or vascularization was observed with PBSS implants. Intramedullary application of a light-curable PBSS is a biocompatible, feasible method for fracture fixation.

The absorption, disposition, and metabolism of [14C]thiophene was investigated in rats following nose-only inhalation exposure at 8000 ppm for 1 h. Under these exposure conditions, it was estimated that approximately 16.3% (493 mumol) of the inhaled thiophene was absorbed from the respiratory system. Within 72 h following exposure, a total of 488 mumol of thiophene equivalents (99% of that retained) was excreted, of which 360.4 mumol (73.9% of the total excreted radioactivity) was in expired air, 120.7 mumol (24.8%) was in urine, 3 mumol (0.6%) was in feces, and 3.7 mumol (0.8%) was in the cage wash. Excretion took place primarily within the first 8 h, during which 91% of the total radioactivity excreted was collected. The thiophene equivalents remaining in tissues at 72 h were estimated to total 5.1 mumol (1.0% of the retained radioactivity). Exhaled radioactivity was identified as thiophene. No 14CO2 was detected in the expired air. After 1 h following exposure, the elimination of thiophene equivalents from plasma was monophasic, with a half-time of 3.6 h. The elimination of thiophene equivalents from blood cells was biphasic, with half-times of 2.9 h and 9.1 d. The blood cells/plasma concentration ratios of thiophene equivalents ranged from 3 to 13, with the higher ratio observed at the 12-h time interval. At 72 h after exposure, blood cells contained the highest concentration of thiophene equivalents, approximately fourfold higher than that of the liver, which contained the second highest concentration. Kidney, heart, and lung contained similar but lower concentrations than liver, while brain, fat, and skeletal muscles contained the lowest concentrations. In summary, this study demonstrates that thiophene was absorbed from the respiratory system, and the majority of the absorbed thiophene was eliminated unchanged in the exhaled air, while a smaller fraction was metabolized and eliminated in urine.