Abstract 12786: Renal Denervation Reduces Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension
Introduction and Hypothesis: We have previously shown that neurohormonal over-activation (i.e. sympathetic nervous system and renin-angiotensin-aldosteron system) accelerates disease progression in pulmonary arterial hypertension (PAH). Renal denervation is a new clinical modality, which may have therapeutic potential in PAH, as it suppresses both neurohormonal systems. Here, we tested the hypothesis that renal denervation ameliorates pulmonary vascular remodeling in experimental PAH.
Methods: PAH was induced in male Wistar rats by a single injection of monocrotaline (60mg/kg; s.c.). Twelve days later, development of PAH was confirmed by echocardiography. PAH-rats were then randomized for renal denervation or sham operation (n=9 /group). At end-of-study (body mass loss >5%), echocardiography was repeated, with additional right ventricular (RV) pressure-volume measurements and histological analysis was performed on lung tissue.
Results: Renal denervation was successful, indicated by a reduction of the noradrenaline content in the kidneys of >90% (measured by ELISA; p<0.001). In renal denervated PAH-rats, compared to sham operated PAH-rats, echocardiography demonstrated significant reduction in estimated RV systolic pressure (77±1 vs. 95±4 mmHg; p<0.01), total pulmonary vascular resistance (Figure 1A) and RV wall thickness (0.7±0.0 vs. 0.9±0.0 mm; p<0.01). In line, RV pressure-volume analysis showed reduction in RV afterload (arterial elastance: 344±23 vs. 493±59 mmHg/ml; p<0.001) and RV end-diastolic elastance (12±1.9 vs. 22±3 mmHg/ml; p<0.01), whereas RV contractility remained unchanged. The extent of pulmonary vascular remodeling was significantly less in the renal denervated PAH-rats (Figure 1B).
Conclusion: Renal denervation reduces pulmonary vascular remodeling and RV afterload in PAH-rats.
Author Disclosures: D. da Silva Goncalves Bos: None. C. Happé: None. I. Schalij: None. W. Pijacka: None. J. F. Paton: None. H. Bogaard: None. N. Westerhof: None. A. (Bert) van Rossum: None. A. Vonk-Noordegraaf: None. F. de Man: None. M. Handoko: None.
- © 2014 by American Heart Association, Inc.