Que Zhu

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.

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 Denervation for Resistant Hypertension Using High-Intensity Focused Ultrasound

Renal denervation (RDN) has emerged as a promising therapy for patients with resistant hypertension and other diseases related to sympathetic overactivation.1 High-intensity focused ultrasound (HIFU) has been demonstrated to be a novel strategy for effective noninvasive deep tissue ablation in clinical practice.2 The exploration of HIFU has expanded to cardiovascular research, such as noninvasive septal and electrophysiological ablations.3,4 We previously reported that efficient RDN can be achieved using the HIFU procedure with an excellent safety profile in a canine model.5 Thus, the clinical use of HIFU-based RDN to treat resistant hypertension should be investigated. This clinical study was approved by the Institutional Ethical Review Committee at The Second Affiliated Hospital of Chongqing Medical University and was registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR-ONC-13003231). The primary efficacy objective was the change in average 24-hour ambulatory systolic blood pressure at 6 months. The primary safety objective was all adverse events during the study. Eligible patients were treated with HIFU-based RDN from August 2013 to May 2014 with 6 months of follow-up. Written informed consent was obtained from all of the enrolled patients. The enrollment criteria included adult patients with resistant hypertension or patients who could not tolerate antihypertensive medications. The participating patients received stable antihypertensive drug regimen for at least 4 weeks before enrollment and were evaluated by ambulatory blood pressure monitoring to exclude the white coat hypertension and pseudohypertension. A complete listing of the key inclusion and exclusion criteria is shown in Table 1. View this table: Table 1. Key Eligibility Criteria Baseline data collection included the medical history, physical examination, review of medications, ambulatory blood pressure monitoring, office blood pressure (BP), Holter monitoring (including heart rate variability [HRV] analysis), renal artery computed tomography angiography, echocardiography, plasma noradrenaline level, and blood chemistries test (including serum creatinine, …

Effects of transmyocardial jet revascularization with chitosan hydrogel on channel patency and angiogenesis in canine infarcted hearts.

The purpose of this study was to investigate whether transmyocardial jet revascularization (TMJR) with chitosan scaffolds retains channel patency and enhances angiogenesis after acute myocardial infarction (AMI) in a canine model. A total of 32 canines were randomly divided into four groups: myocardial infarction (MI), normal saline (NS), chitosan hydrogel (CH), and chitosan plus growth factor (CH + GF) groups. TMJR was performed surgically using a needle-free injector from the epicardium of canines in the NS, CH, and CH + GF groups; channels were filled with NS, CH, and CH + GF, respectively. After 6 weeks, the patency of the channels and angiogenesis around the channels were assessed by hematoxylin-eosin staining, immunohistochemistry, and Massons trichrome staining. Results suggest that the channels in the CH and CH + GF groups may retain patency with luminal endothelization. Moreover, the vessel densities of the NS, CH, and CH + GF groups were significantly higher than that of the MI group, and that of the CH + GF group was the highest (p < 0.05). This study suggests that TMJR with chitosan scaffolds may help retain transmyocardial channel patency and enhance angiogenesis after AMI in canines.

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.

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 Evans 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.