Book of Abstracts - New Frontiers 2022

Abstracts of oral presentations

EFFECT OF RENAL DENERVATION ON LEFT AND RIGHT VENTRICULAR FUNCTION IN TRANSGENIC HYPERTENSIVE RATS WITH HEART FAILURE INDUCED BY VOLUME OVERLOAD M. Miklovič 1,3 , O. Gawryś 1 , P. Kala 2 , Z. Honetschlägerová 1 , Š. Jíchová 1 , Z. Vaňourková 1 , Z. Husková 1 , S. Kikerlová 1 , H. Maxová 3 , D. Sedmera 3 , T. Mráček 4 , V. Melenovský 1 1 Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 2 Motol University Hospital, Prague, Czech Republic; 3 Charles University, Prague, Czech Republic; 4 Czech Academy of Sciences, Prague, Czech Republic Mechanical and chemical removal of neural fibers around renal arteries (RDN) destructs both afferent nerve fibers that regulate central sympathetic nervous outflow and efferent fibers that regulate the renal renin angiotensin system and neprilysin. RDN has known hypotensive effects and experimental data show that this therapy can prolong the survival rate in animal models of heart failure. However, the effect of renal denervation on the function of the right and left ventricle in the course of heart failure is still poorly known. The aim of the study was to determine the effect of renal denervation on the function of the right and left ventricle in hypertensive rats with volume overload induced by aorto-caval fistula (ACF). Methods: In the first week of the experiment, heart failure was induced in Ren-2 transgenic rats (TGR), a model of angiotensin II-dependent hypertension by ACF at the animal age of 8 weeks. Bilateral renal denervation was performed chemically and mechanically in the second week of the experiment. Two weeks after RDN, the functions of the left and right ventricle were measured by simultaneous biventricular pressure-volume analysis, and the animals were examined using echocardiography each week. After in vivo experiments, animals were decapitated and organs were collected for molecular analysis. RDN in ACF rats significantly reduced lungs congestion and both left and right ventricular hypertrophy. In sham-operated rats without heart failure, RDN had an antihypertensive effect, which was reflected in decreased maximum pressure in the left ventricle (by 13.43 mmHg, P < 0.05). In ACF rats, RDN decreased the diameter and filling volumes in both systole and diastole of the left ventricle after two weeks. RDN in ACF rats significantly reduced end-diastolic pressure (by 1.52 mmHg, P < 0.05) and maximum pressure (by 5.71 mmHg, P < 0.05) in the right ventricle but not in the left ventricle. RDN in ACF rats also improved contractility in both ventricles which was observed as an increase in parameters of systolic function ESPVR and PRSW. In ACF rats we observed increased levels of norepinephrine in the kidney and decreased levels in both ventricles of the heart compared with sham-operated rats. We also investigated the norepinephrine metabolizing enzyme monoamine oxidase A, which was shown to be increased in both ventricles of ACF rats compared to sham group. RDN in ACF rats significantly reduced renal norepinephrine levels and increased cardiac norepinephrine levels. Furthermore, we focused on the neprilysin signaling pathway in kidneys and observed inhibition of neprilysin activity after renal denervation in ACF rats. In conclusion, our results showed cardioprotective effects of renal denervation in hypertensive transgenic rats with heart failure. Our data suggest that renal denervation could be a promising method in the treatment of both right and left ventricular heart failure.

Keywords: heart failure, hypertension, renal denervation

Funding:Supported by Ministry of Health, Czech Republic - conceptual development of research organization („Institute for Clinical and Experimental Medicine – IKEM, IN 00023001“), grant nr. AZV NU21-02-00402 and Second Faculty of Medicine, Charles University (GA UK: 304121).

45