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Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label，blinded-outcome，randomised trial
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Original Research2019 May 7. pii: EIJ-D-18-01082.

JOURNAL：EuroIntervention. Article Link

Pulmonary Artery Denervation Using Catheter based Ultrasonic Energy

Rothman A, Jonas M, Castel D et al. Keywords: pulmonary artery denervation; pulmonary hypertension

ABSTRACT

AIMS -  Pulmonary arterial hypertension is a devastating disease characterized by pulmonary vascular remodelling and right heart failure. Radio-frequency pulmonary artery denervation (PDN) improves pulmonary hemodynamics in pre-clinical and early clinical studies, however denervation depth is limited. High-frequency non-focused ultrasound can deliver energy to the vessel adventitia, sparing the intima and media. We therefore investigated the feasibility, safety and efficacy of ultrasound PDN.

 

METHODS AND RESULTS -  Histological examination demonstrated that innervation of human pulmonary arteries are predominantly sympathetic (71%), with >40% of nerves at a depth of >4mm. Finite element analysis of ultrasound energy distribution and ex-vivo studies demonstrated generation of temperatures >47ºC to a depth of 10mm. In domestic swine PDN reduced mean pulmonary artery pressure induced by thromboxane A2 in comparison to sham. No adverse events were observed to 95-days. Histological examination identified structural and immunohistological alterations of nerves in PDN treated animals, with sparing of the intima and media and reduced tyrosine hydroxylase staining 95-days post-procedure indicating persistent alteration of the structure of sympathetic nerves.

 

CONCLUSIONS -  Ultrasound PDN is safe and effective in the pre-clinical setting, with energy delivery to a depth that will permit targeting sympathetic nerves in humans.

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