Does a small-diameter rod-type tunneler reduce postoperative swelling? An evaluation using a canine arteriovenous graft model.

PURPOSE: Sheath-type tunnelers are frequently used to create vascular access using vascular grafts. However, during vascular access creation, tunnelers damage the surrounding tissues, consequently causing problems, such as swelling, failure to heal, and infection. This study evaluated a novel rod-type tunneler that was designed to prevent tunneler-related tissue damage and its sequelae. METHODS: We developed a small-diameter rod-type tunneler that reduces injuries during subcutaneous tunnel creation. The rod diameter of this tunneler is smaller than the vascular graft diameter being implanted. It has a structure in which a vascular graft is implanted at a target site by grasping and pulling the vascular graft. Three dogs were used in the experiment, and arteriovenous grafts were created using a rod-type and a sheath-type tunneler on the left and right thighs, respectively, with a different type of commercially available graft used in each dog. The edema of the tissues surrounding the vascular graft was measured at 11 sites by ultrasonography at prespecified intervals. RESULTS: Compared with implantation using a sheath-type tunneler, when the self-sealing Rapidax II was implanted using the small-diameter rod-type tunneler, the postimplantation edema (degree of change) decreased by 28-53% and 80-247% in the peri-vascular-graft area and within the loop, respectively. The MAXIFLO and SEALPTFE did not significantly reduce postoperative edema but exhibited a tendency for improved postimplantation tissue healing. CONCLUSIONS: The reduced-diameter rod-type tunneler may be a useful device for vascular graft implantation.

Method for Combined Observation of Serial Sections of Stented Arteries Embedded in Resin by Light Microscopy and Transmission Electron Microscopy.

We have developed a new method for obtaining information on whole tissues by light microscopy (LM) and ultrastructural features by transmission electron microscopy (TEM). This method uses serial sections of a stented artery embedded in resin. Stents were implanted in porcine coronary arteries in this study. The heart was perfusion fixed in a 2% paraformaldehyde and 1.25% glutaraldehyde mixed solution. The stented artery was then removed, fixed in 1% osmium, embedded in Quetol 651 resin, and sectioned serially. For LM, the black color of osmium was removed from the section by immersion in periodic acid and hydrogen peroxide after deplasticization. These sections were stained with hematoxylin and eosin and Elastica-Masson trichrome stain. For TEM, thin sections were re-embedded in Quetol 812 resin by the resupinate method and cut into ultrathin sections. A clear, fine structure was obtained, and organelles, microvilli, and cell junctions in the endothelium were easily observed. The combined observation of adjacent specimens by LM and TEM enabled us to relate histopathological changes in the millimeter scale to those in the nanometer scale.

Acute changes in histopathology and intravascular imaging after catheter-based renal denervation in a porcine model.

OBJECTIVES: We first aimed to identify the histopathological changes occurring immediately after renal denervation (RDN) with radiofrequency energy, and then to assess the feasibility of determining procedural success using currently available clinical intravascular imaging techniques. BACKGROUND: Catheter-based RDN has been used as an alternative therapy for hypertension. However, no practical endpoint to determine procedural success during treatment has been established. METHODS: A total of 39 ablation lesions were induced in vivo in eight porcine renal arteries and a total of 15 ablation lesions were induced ex vivo in five excised porcine renal arteries with a radiofrequency delivery device. Acute histological changes and appearance on intravascular imaging of the lesions were investigated with light microscopy, transmission electron microscopy, intravascular ultrasound (IVUS), and optical frequency domain imaging (OFDI). RESULTS: Marked changes were noted in media, adventitia, and perirenal-arterial nerves immediately after in vivo ablation. Changes visualized on IVUS were characterized by focal adventitial thickening comprising a relatively echogenic layer around a heterogeneously hypoechoic interior region, and on OFDI as disappearance of the external elastic membrane signals with high scattering of signals in the surface layer. The changes after ex vivo ablation were histopathologically identical to those from in vivo ablation. There were statistically significant positive correlations in measured dimensions (area, depth, width, and diameter) of ablation lesions between histopathology and IVUS/OFDI findings (Pearson correlation coefficients = 0.69-0.77). CONCLUSIONS: These findings suggest that observation of treated renal arteries by IVUS or OFDI immediately after RDN improves the success rate of RDN.

Histopathological background data of the systemic organs of CLAWN miniature swine with coronary artery stent implantation.

The aim of this study was to identify potential changes that could occur during histological evaluations of CLAWN miniature swine, with potential consequences for subsequent experiments. The systemic organs from male and female CLAWN miniature swine (16.3-42.3 months old) that had been used in long-term studies of coronary stent implantation were examined histologically. Commonly observed histopathological findings were testicular/epididymal atrophy, cyst-like follicles in the ovaries, hemosiderin deposition in the spleen, lipofuscin deposition in the proximal tubular epithelia and presence of eosinophilic globules in the Bowman's space and the lumen of the proximal tubules in the kidneys, and cellular infiltration in several organs, including the eyelids, respiratory organs, and digestive tract. However, none of these changes were serious enough to indicate a significant impact on research. In conclusion, this study identified CLAWN miniature swine as a suitable animal model for various experiments.

Vascular endothelium damage from catheter-induced mechanical stimulation causes catheter sleeve formation in a rabbit model.

BACKGROUND: Intravenous catheters are widely used but are often removed due to complications associated with catheter sleeve formation. A catheter sleeve can develop from a thrombus, and catheter-induced vascular endothelium damage may be a critical factor for thrombus formation. We investigated the effect of catheter-induced mechanical stimulation on venous endothelial cells and catheter sleeve formation and the efficacy of anti-thrombogenic technology for preventing catheter sleeve formation in vivo. METHODS: We surgically implanted poly(2-methoxyethyl acrylate)-coated and uncoated catheters with and without a stylet into the right external jugular vein of a rabbit model for 14 days. Catheter sleeve formation and the ratio of residual venous endothelial cells were compared using histological examination and immunostaining with an anti-CD31 antibody, respectively. RESULTS: Stiffening an uncoated catheter with a stylet induced catheter sleeve formation along more than two-thirds of the length of the catheter. The ratios of residual venous endothelial cells at the tip of uncoated catheters with and without a stylet were 3% and 36%, respectively. While poly(2-methoxyethyl acrylate) coating also reduced the ratio of venous endothelial cells at the tip of the stiffened catheter (12%), it prevented external thrombus and catheter sleeve formation. CONCLUSION: High levels of mechanical stimulation can affect catheter-related thrombosis and promote catheter sleeve formation, and anti-thrombogenic technology such as a poly(2-methoxyethyl acrylate) coating reduces thrombus formation and can prevent catheter sleeve formation on stiffened catheters. Further studies are required to determine the maximum degree of venous endothelial cell damage before catheter sleeve formation and to compare other anti-thrombogenic technologies with poly(2-methoxyethyl acrylate) for preventing catheter sleeve formation.

Accurate Depth of Radiofrequency-Induced Lesions in Renal Sympathetic Denervation Based on a Fine Histological Sectioning Approach in a Porcine Model.

BACKGROUND: Ablation lesion depth caused by radiofrequency-based renal denervation (RDN) was limited to <4 mm in previous animal studies, suggesting that radiofrequency-RDN cannot ablate a substantial percentage of renal sympathetic nerves. We aimed to define the true lesion depth achieved with radiofrequency-RDN using a fine sectioning method and to investigate biophysical parameters that could predict lesion depth. METHODS AND RESULTS: Radiofrequency was delivered to 87 sites in 14 renal arteries from 9 farm pigs at various ablation settings: 2, 4, 6, and 9 W for 60 seconds and 6 W for 120 seconds. Electric impedance and electrode temperature were recorded during ablation. At 7 days, 2470 histological sections were obtained from the treated arteries. Maximum lesion depth increased at 2 to 6 W, peaking at 6.53 (95% confidence interval, 4.27-8.78) mm under the 6 W/60 s condition. It was not augmented by greater power (9 W) or longer duration (120 seconds). There were statistically significant tendencies at 6 and 9 W, with higher injury scores in the media, nerves, arterioles, and fat. Maximum lesion depth was positively correlated with impedance reduction and peak electrode temperature (Pearson correlation coefficients were 0.59 and 0.53, respectively). CONCLUSIONS: Lesion depth was 6.5 mm for radiofrequency-RDN at 6 W/60 s. The impedance reduction and peak electrode temperature during ablation were closely associated with lesion depth. Hence, these biophysical parameters could provide prompt feedback during radiofrequency-RDN procedures in the clinical setting.

Vascular responses to a biodegradable polymer (polylactic acid) based biolimus A9-eluting stent in porcine models.

AIMS: The time-dependent changes in endothelial and healing properties of coronary arteries implanted with a biodegradable polymer-based biolimus A9-eluting stent (BioPol-BES) have not been investigated. We evaluated the short-term and the long-term in vivo response of BioPol-BES, as compared to a permanent polymer-based sirolimus-eluting stent (PermPol-SES), and a bare metal stent (BMS). METHODS AND RESULTS: Overlapping stents were placed in 33 swine (n=11 for BES, SES, and BMS, respectively) for two and four weeks and single stents in 30 miniature pigs (n=18 for BES, n=9 for SES, n=3 for BMS) for three, nine and 15-month evaluations. The vessel patency, arterial healing and endothelialisation were assessed by angiography, histopathology and scanning electron microscopy. At four weeks, the endothelialisation at overlapping stent regions was greater with BioPol-BES (87.8±3.7%) and BMSs (98.0±0.4%) than with PermPol-SES (66.4±3.2%). The inflammation score in vessels implanted with single BioPol-BES increased slightly from three to 15 months (0.00±0.00 to 0.28±0.14), while this increase was more pronounced with PermPol-SES (0.11±0.07 to 1.56±0.68). Compared to BMS moderate lymphocyte infiltration was seen with BioPol-BES, and marked granulomatous formation with PermPol-SES. CONCLUSIONS: The level of endothelial coverage in BioPol-BES was comparable to BMS at four weeks, with no significant increase of inflammatory reaction up to 15 months.