肺动脉高压
Original Research2019 May 7. pii: EIJ-D-18-01082.
JOURNAL:EuroIntervention. Article Link
Rothman A, Jonas M, Castel D et al. Keywords: pulmonary artery denervation; pulmonary hypertension
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.