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Hypertension is one of the most common medical conditions amongst people in developed countries, and it can have fatal consequences for the cardiovascular system.
Most patients suffer from resistant hypertension and cannot be treated by common antihypertensive drugs. Recent findings have shown that overactivity of the sympathetic nervous system plays an important role in the development of hypertension.
This has lead scientists to explore and develop new minimal invasive treatment methods to degenerate renal sympathetic nerve fibres located around the renal arteries, thereby preventing this overactivity. One established method is catheter-based radiofrequency ablation. An endovascular catheter is inserted in the femoral artery in the inguinal region and pushed forward to the renal artery. Radiofrequency energy is then applied to the adventitia of the renal artery. However, this approach is unavailable to patients who have certain anatomic characteristics. This has therefore led us to search for new, non-invasive treatment methods for renal denervation.
Magnetic resonance-guided, high-intensity focused ultrasound (MRg HIFUS) is a non-invasive, ablative method that is currently used primarily for the treatment of uterine fibroids. We therefore undertook this study to evaluate the safety and efficacy of MR-guided high-intensity focused ultrasound for renal sympathetic denervation in a porcine model. A total of ten pigs were used in this study, one of which was a sham pig and was not treated. During the MRg HIFUS intervention all pigs were placed under general anaesthesia using propofol. They were then treated with MRg HIFUS along the right renal artery. Two of the pigs were sacrificed straight after the MRg HIFUS treatment, the other eight pigs were sacrificed 28 days later. Both kidneys were removed and homogenized using formic acid. Samples of the kidneys were then examined for their concentration of norepinephrine using high pressure liquid chromatography and electrochemical detection.
Renal arteries and urethras were preserved in formalin, histologically processed, and stained with HE and EvG staining. Degenerative sympathetic nerve fibres could be easily detected after this staining. In three of the nine pigs perivascular oedema indicating thermal tissue damage was diagnosed on the T2w FSE sequences taken after the HIFUS treatment. Furthermore, the norepinephrine concentrations in the treated kidneys of the pigs did not drop significantly, something that would also have indicated the treatment was successful. During the histological examination, perineural fibrosis, indicating degenerated sympathetic nerve fibres, was visible in one of the pigs.
All pigs tolerated the treatment very well and there were no serious complications.
Three of the nine pigs treated displayed superficial skin burns following the MRg HIFUS treatment. The results showed that pigs are not suitable subjects for MRg HIFUS treatment as a result of long lumbar transverse processes and a dominant fascia thoracolumbalis. Nine pigs treated with MRg HIFUS showed changes caused by thermal damage, concentrated around the transverse process of the lumbar vertebrae.
The long transverse processes of the pigs’ lumbar vertebrae complicated the use of a straight ultrasound beam, limited the acoustic window of the HIFUS and caused energy absorption and reflection. The fat tissue in close proximity to the renal arteries also made the use of magnetic resonance thermometry, and therefore temperature mapping in this area, impossible. This study provided evidence that MRg HIFUS could not be used successfully as a treatment method to produce renal denervation in pigs.
In one pig we assume a potential success of renal sympathicolysis.
However, the high potential of this non-invasive therapy technique could still be clearly observed. The minimal and infrequent complications, the safety of the technique, and the visualisation on account of the combination with the MRI are strong arguments for further studies to be conducted that explore the possibility of using MRg HIFUS to induce renal denervation. In such studies, however, pigs should not be used as subjects.