Use the right kidney contour as a landmark in adrenal vein sampling.

Adrenal Vein Sampling (AVS) is the gold standard for categorizing primary aldosteronism (PA). However, catheterization of the right adrenal vein (RAV) is challenging due the small size and variable location. This study aims to explore the relationship between the RAV orifice and the right kidney contour (RKC) on fluoroscopy, thus evaluating the potential of use the RKC as an anatomic marker for localizing RAV. Imaging data of 107 PA patients with successful bilateral AVS were retrospectively analyzed. Based on the body mass index (BMI), all patients were divided into the Normal Group (BMI < 24 kg/m2), Overweight Group (24 kg/m2 ≤ BMI < 28 kg/m2) and Obese Group (BMI ≥ 28 kg/m2). At the anterior view, the height level of RAV orifice was determined relative to vertebral bodies and disks. The distance from the RAV orifice to the upper edge of RKC was measured manually. The RAV orifice height level was mainly distributed from vertebral T11 to T12 (90.6%), and tended to be higher in patients with a larger BMI. The mean distance from the RAV orifice to the upper edge of RKC was 13.9±7.8mm, and had no difference among Normal group (n = 53, 14.1±8.2mm), Overweight group (n = 39, 13.7±8.0mm), and Obese group (n = 15, 13.9±5.5mm) (p = 0.981). Based on these findings, the RKC might be used as a landmark for localizing RAV on fluoroscopy, which is conductive to narrow down the exploration range and increase the success rate of RAV catheterization.

Downregulating the P2X3 receptor in the carotid body to reduce blood pressure via acoustic gene delivery in canines.

The purinergic P2X3 receptor in the carotid body (CB) is considered a new target for treating hypertension, although approaches for targeted regulating P2X3 receptor expression are lacking. Here, we explored the feasibility of targeted P2X3 receptor down-regulation in CBs by localized low-intensity focused ultrasound (LIFU)-mediated gene delivery to reduce the blood pressure. Thirty-two Kunming canines were randomly assigned to the treatment group (n = 14), negative control group (n = 10), LIFU + cationic microbubbles group (n = 4), and LIFU-only group (n = 4). Plasmid-loaded cationic microbubbles were injected and bilateral CBs were irradiated with a LIFU-based transducer. Flow cytometry showed that 33.15% of transfected cells expressed the green fluorescent protein reporter gene. T7 endonuclease I assays showed an insertion-deletion rate of 8.30%. The P2X3 receptor mRNA- and protein-expression levels in CBs decreased by 56.31% and 45.10%, respectively, in the treatment group. Mean systolic (152.5 ± 3.0 vs 138.0 ± 2.9 mm Hg, P = 0.003) and diastolic (97.8 ± 1.5 vs 87.2 ± 2.3 mm Hg, P= 0.002) blood pressures reduced on day 14 in the treatment group, compared with the baseline values, whereas no effects were observed with LIFU treatment or cationic microbubbles injection alone. Canines treated with this strategy exhibited no local or systemic adverse events. Thus, LIFU-mediated gene delivery to CBs successfully modulated CB function and reduced blood pressure in a canine model, suggesting a new possibility for treating hypertension and further clinical translation.

Carotid body enlargement in hypertension and other comorbidities evaluated by ultrasonography.

BACKGROUND: Carotid body hyperactivity is important for sympathetic-related diseases and carotid body volume may partly reflect carotid bodies' activity. Our objective was to identify the association between carotid body volume and hypertension or other sympathetic-related diseases. METHODS: Consecutive individuals, undergoing carotid ultrasonography, who were eligible for the inclusion criteria were included. The bilateral carotid bodies were detected and volumetric parameters were measured by carotid ultrasonography in clinical. Clinical data of included participants were collected and analysed. RESULTS: A total of 1226 consecutive individuals underwent carotid ultrasonography. Carotid bodies were detected as solid, pebble-shaped, hypoechoic structures and the overall carotid body detection rate was 78.7% (965/1226). Univariate and multivariate regression analyses indicated that hypertension, chronic heart failure (CHF), chronic lung disease, smoking and high BMI were positively associated with carotid body enlargement. Compared with controls (2.63 µl), carotid body volume was significantly elevated in simple hypertensive (3.11 µl, P < 0.001), simple CHF (3.27 µl, P = 0.004) and simple smoking (3.47 µl, P < 0.001) groups. Moreover, the individuals with three comorbidities (4.05 µl) had significantly larger carotid bodies than those with one (3.23 µl, P < 0.001) or two comorbidities (3.46 µl, P = 0.017), suggesting that there existed a cumulative effect of comorbidities on carotid body volume. CONCLUSION: Carotid body enlargement is strongly associated with hypertension and other sympathetic-related diseases or risk factors, and carotid body volume evaluated by carotid ultrasonography may be further explored as a promising screening and evaluation predictor for carotid body modulation therapy in patients with hypertension and other sympathetic-related diseases.

Cardiac Denervation for Arrhythmia Treatment with Transesophageal Ultrasonic Strategy in Canine Models.

Stellate ganglion (SG) modification has been investigated for arrhythmia treatment. In this study, transesophageal SG imaging and intervention were explored using a homemade 30F integrated focused ultrasonic catheter in healthy mongrel canines in vivo. Anatomic details of SGs were ultrasonically imaged and evaluated. SG had a heterogeneous echoic structure and characteristic profiles sketched by hyper-echoic outlines in an ultrasonogram. Left SGs in the experimental group were successfully ablated through the esophagus under ultrasonic guidance provided by the catheter itself. Two weeks after the ablation, the QT and QTc of the experimental group decreased compared with those of the sham group and at baseline (both p values < 0.001). Histologic examination revealed that left SGs were destroyed. No major complications were observed. This approach may be further explored as a method for ganglia remodeling evaluation and as a strategy of ganglia modification for arrhythmia and for other diseases.

Anatomy and neural remodeling of the renal sympathetic nerve in a canine model and patients with hypertension.

BACKGROUND: The role of renal sympathetic nerve (RSN) in hypertension should be better understood. We aimed to three-dimensionally reconstruct the renal nerves, and explore its anatomical and histochemical characteristics in hypertensive canine model and patients. METHODS: Renal arteries with surrounding tissue were collected from canines and cadavers with or without hypertension. Serial renal artery hematoxylin-eosin sections were used for three-dimensional reconstruction, and morphological parameters were collected and analyzed. RESULTS: In hypertensive canines, the mean renal nerve number was 26.71 ±â€Š5.68 versus 19.84 ±â€Š5.68 in controls (P = 0.02), and the middle renal nerve volume was 5.31 ±â€Š2.13 versus 2.60 ±â€Š1.00 µl in controls (P = 0.01). Renal tissue norepinephrine concentrations, tyrosine hydroxylase and substance P immunoreactivity in RSN, and growth-associated protein 43 immunoreactivity in renal ganglion were significantly increased in hypertensive canines. In humans, the renal nerve was evenly distributed along the renal artery in a network pattern. The renal ganglion volume was 72.75 ±â€Š33.43 in hypertensive patients versus 37.04 ±â€Š23.95 µl in controls (P = 0.029) and the mean neuronal size in renal ganglion was 1187.3 ±â€Š219.9 µm in patients versus 714.8 ±â€Š142.7 µm in controls (P = 0.002). Tyrosine hydroxylase immunoreactivity in the RSN was 0.153 ±â€Š0.014 in patients versus 0.104 ±â€Š0.019 in controls (P = 0.013). Growth-associated protein 43 immunoreactivity in the renal ganglion was 86 612.8 ±â€Š14 642.0 in patients versus 33 469.8 ±â€Š15 666.8 µm/mm in controls (P < 0.001). CONCLUSION: Our study suggests that RSN and renal ganglion histological remodeling occurs in individuals with hypertension and the distal segment or branches of renal artery might be a promising therapeutic target for RSN modulation therapy.

Septal ablation induced by transthoracic high-intensity focused ultrasound in canines.

BACKGROUND: High-intensity focused ultrasound (HIFU) can achieve accurate and focused deep tissue ablation through an extracorporeal emission. Cardiac ablation using HIFU applied transthoracically must overcome potential interference from intervening thoracic structures. The aim of this study was to explore the efficacy and safety of septal ablation that was induced using transthoracic HIFU. METHODS: Twenty-one canines were pretreated to improve acoustic transmission. Single ablations were induced by targeting transthoracic HIFU with acoustic power of 400 W for 3 sec at the middle and basal septum in eight canines. Extended ablations were performed to create larger lesions at the basal septum in eight more canines. The three-dimensional morphology of a basal septum lesion induced by a single ablation was analyzed. The temperature at the ablative targets was measured in the other five canines. RESULTS: The cardiomyocytes in the lesions underwent necrosis with a clear boundary. The three-dimensional morphology of the lesions appeared approximately as ellipsoids with a flatter endocardial side. The peak temperature at a power of 400 W for 3 sec was 93.27 ± 2.54°C, and it remained >50°C for nearly 10 sec. No procedure-related complications were observed. CONCLUSIONS: Ultrasound-guided transthoracic HIFU has the potential to safely create small dot or large mass lesions in the septum without a thoracotomy or a catheter.

Noninvasive renal sympathetic denervation by extracorporeal high-intensity focused ultrasound in a pre-clinical canine model.

OBJECTIVES: This study investigated the feasibility of noninvasive renal sympathetic denervation (RSD) by using the novel approach of extracorporeal high-intensity focused ultrasound (HIFU). BACKGROUND: Catheter-based RSD has achieved promising clinical outcomes. METHODS: Under the guidance of Doppler flow imaging, therapeutic ablations (250 W × 2 s) were performed by using extracorporeal HIFU on the bilateral renal nerves (36.3 ± 2.8 HIFU emissions in each animal) in a mean 27.4-min procedure in 18 healthy canines of the ablation group. Similar procedures without acoustic energy treatment were conducted in 5 canines of the sham group. The animals were killed on day 6 or 28. Blood pressure (BP), plasma noradrenaline (NA) level, and renal function were determined on days 0, 6, and 28. Pathological examinations were performed on all retrieved samples. RESULTS: All of the animals survived the treatment. After ablation, BP and NA significantly decreased compared with the baseline values (BP changed -15.9/-13.6 mmHg, NA changed -55.4% [p < 0.001] 28 days after ablation]) and compared with the sham group on days 6 and 28. Ablation lesions around the renal artery adventitia were observed on day 6. A histological examination revealed the disruption of nerve fibers, necrosis of Schwann cells and neurons, and apparent denervation on day 28. No procedure-related complications were observed. CONCLUSIONS: Effective RSD was successfully achieved by using the extracorporeal HIFU method in canines. Thus, noninvasive HIFU may be further explored as an important and novel strategy for RSD.

The feasibility and safety of transendocardial gene injection in canine using a multifunctional intracardiac echocardiography catheter.

BACKGROUND: Transendocardial gene delivery may expose patients to the risk of pericardial perfusion due to excessive needle injections. This study investigated the feasibility and safety of transendocardial gene injection using a newly developed multifunctional intracardiac echocardiography catheter. METHODS: This new system integrated intracardiac echocardiography, a retractable 29-G needle, and other accessories into a single catheter (10F) that could be delivered into the left ventricle via a retrograde aortic approach. In three canines, the catheter was used to inject 0.2 ml of Evan's blue; six canines received myocardial injections of plasmid containing the EGFP transgene. In addition, two canines received transendocardial injections of a pAdTrace-bFGF plasmid. All canines receiving gene delivery were sacrificed after 3 days. The hearts were harvested for gross, histological examination and gene expression assessment. RESULTS: This catheter provided visual guidance for accurate needle-tip positioning within the target myocardium; the needle position was subsequently confirmed by microbubble infusion. No animal had pericardial effusion or sustained ventricular arrhythmia. Tissue staining showed well-demarcated margins within the target myocardium. In animals injected with pEGFP-N1, confocal microscopy demonstrated successful gene expression. In zones where pAdTrace-bFGF was injected, immunohistochemistry also showed positive staining. Compared to normal tissue (0.38±0.04), RT-PCR showed high levels of bFGF expression (0.63±0.02) in the target area (P<0.01). CONCLUSIONS: Transendocardial gene injection using a multifunctional intracardiac echocardiography catheter is feasible and could improve procedure-related safety which may provide a new strategy for transgene delivery in future.

A new strategy for septal ablation with transendocardial ethanol injection using a multifunctional intracardiac echocardiography catheter: a feasibility study in canines.

OBJECTIVES: To evaluate the feasibility and safety of a novel multifunctional intracardiac echocardiography catheter for target septal ablation with transendocardial ethanol injection in canines. BACKGROUND: Percutaneous transluminal septal myocardial ablation has been the primary catheter-based strategy for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). However, inherent limitations of the technique have reduced its therapeutic efficacy. METHODS: A new catheter (10 F), integrated with a nitinol needle (29 G) and a 6.5-10-MHz, 32-element, side-fire ultrasound imaging transducer, was delivered into the right ventricle in nine canines and the left ventricle in three canines. A 0.3-ml microbubble and 0.5-1.5 ml absolute ethanol were sequentially injected into the interventricular septum. Electrocardiograph recordings were obtained during the whole procedure. Three hours after this operation, the heart was harvested for gross and histological examination. RESULTS: In all canines, the catheter provided the structural support and helped guide proper needle position within the septum. The microbubble further allowed the confirmation of the needle location through focal echo-density enhancement. Different amounts of ethanol infusion produced a dose-related effect on myocardial ablation. Macroscopic examination showed that the target myocardium became pale with a distinct border between lesions and normal tissue. Hematoxylin and eosin staining further confirmed necrosis within the injection region. CONCLUSIONS: Transendocardial ethanol injection at the interventricular septum resulted in controlled myocardial infarction. In addition, the injection depth could be visually followed using this new system, which may provide a safer and more intuitive method for the treatment of HOCM or other cardiomyopathies.