Development and Evaluation of a Disease Large Animal Model for Preclinical Assessment of Renal Denervation Therapies

Animals

Armando Tellez¹  ArmandoPérez de Prado²  AnaIsabel Cortina-Rivero²  Carlos Cuellas-Ramón²  Felipe Fernández-Vázquez²  Marta Regueiro-Purriños²  María López-Benito²  JoséManuel Gonzalo-Orden²  Rodrigo Estévez-Loureiro²  José R Altonaga²  Claudia Pérez-Martínez²  David Viñuela-Baragaño² 

[1] Alizée Pathology LLC., Thurmont, MD 21788, USA;Fundación Investigación Sanitaria de León, Hospital Universitario de León—Instituto de Biomedicina (IBIOMED), Universidad de León, 24071 León, Spain;

关键词: hypertension;    DOCA;    renal denervation;    radiofrequency;    swine;    histology;   

DOI  :  10.3390/ani10091446

来源: DOAJ

【 摘 要 】

New-generation catheters-based renal denervation (RDN) is under investigation for the treatment of uncontrolled hypertension (HTN). We assessed the feasibility of a large animal model of HTN to accommodate the human RDN devices. Ten minipigs were instrumented to measure blood pressure (BP) in an awake-state. HTN was induced with subcutaneous 11-deoxycorticosterone (DOCA, 100 mg/kg) implants. Five months after, the surviving animals underwent RDN with the Symplicity^® system. Norepinephrine (NE) renal gradients were determined before and 1 month after RDN. Renal arteries were processed for histological (hematoxylin-eosin, Movat pentachrome) and immunohistochemical (S100, tyrosine-hydroxylase) analyses. BP significantly rose after DOCA implants. Six animals died prematurely, mainly from infectious causes. The surviving animals showed stable BP levels after 5 months. One month after RDN, nerve damage was showed in three animals, with impedance drop >10%, NE gradient drop and reduction in BP. The fourth animal showed no nerve damage, impedance drop <10%, NE gradient increase and no change in BP. In conclusion, the minipig model of DOCA-induced HTN is feasible, showing durable effects. High mortality should be addressed in next iterations of this model. RDN may partially offset the DOCA-induced HTN. Impedance drop and NE renal gradient could be markers of RDN success.

【 授权许可】

Unknown