Study Of Correlation And Mechanism Between Renal Impairment And Atrial Fibrillation Occurrence

Background and ObjectivesThe number of patients with atrial fibrillation (AF) and chronic kidney disease (CKD) are increasing sharply. In recent years, many studies found that there may be a close correlation between these two diseases. Activation and overactivity of sympathetic nervous system (SNS) may be one of the common pathogenic mechanisms in these two kinds of conditions. Hypersympathetic activity induced by renal impairment (RI) may be involved directly in atrial electrophysiological changes and indirectly in the activation of renin-angiotensin-aldosterone system (RAAS) to enhance AF occurrence. Renal denervation (RDN) therapy which is a kind of method to reduce the activity of SNS, may become a breakthrough point for the treatment of AF combined with RI. The present study was designed to clarify of the correlation between RI and AF occurrence through animal experiment, and to explore the possible internal mechanisms, especially the role of SNS. It will provide a new thinking for clinical treatment of AF combined with RI.MethodsPart One:Unilateral RI was induced in beagles by embolization of small branches of the renal artery in the left kidney for 2 weeks using gelatin sponge granules in the model group (n=5). The sham group (n=5) underwent the same procedure, except for embolization. Parameters associated with RI and renal function were tested, cardiac electrophysiological parameters, blood pressure (BP), left ventricular pressure, and AF vulnerability were investigated. The activity of the SNS, RAAS, inflammation, and oxidative stress were measured. Histological studies associated with atrial interstitial fibrosis were performed.Part Two:Unilateral RI was induced in beagles by embolization of small branches of the renal artery in the right kidney using gelatin sponge granules in Model (n=6) and RDN group (n=6). The Sham group (n=6) underwent the same procedure, except for embolization. Then animals in RDN group underwent radiofrequency ablation of the renal sympathetic nerve. Cardiac electrophysiological parameters, BP, left ventricular end-diastolic pressure (LVEDP), AF inducibility, the activity of the SNS, RAAS, inflammation and oxidative stress, and atrial interstitial fibrosis were measured.ResultsPart One:Embolization of small branches of the renal artery in the left kidney led to ischemic RI. The following changes occurred after embolization. (1) Heart rate and P wave duration were increased. (2) BP and left ventricular systolic pressure (LVSP) were elevated. (3) The atrial effective refractory period (AERP) and antegrade Wenckebach point were shortened. (4) Episodes and duration of AF, as well as atrial and ventricular rate during AF were increased in the model group. (5) Plasma levels of norepinephrine, renin, and aldosterone were increased, angiotensin â…¡ and aldosterone levels in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced after 2 weeks of embolization in the model group.Part Two:We observed 5 main findings. (1) Embolization of small branches of the renal artery in the right kidney led to ischemic RI. (2) Heart rate, P wave duration and BP were increased by RI, which were prevented or attenuated by RDN. (3) AERP was shortened and AF inducibility was increased by RI, which were prevented by RDN. (4) Antegrade Wenckebach point was shortened, atrial and ventricular rates during AF were increased by RI, which were attenuated or prevented by RDN. (5) Levels of norepinephrine, renin and aldosterone in plasma, norepinephrine, angiotensin â…¡, aldosterone, interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP) and fibrosis in atrial tissue were elevated by RI, which were attenuated by RDN.Conclusions1. We successfully established an in vivo model of RI with mild renal insufficiency in a large animal and showed that AF was associated with RI with mild renal insufficiency in this model.2. Using this model, we showed that hypersympathetic activity may facilitate the initiation of RI-associated AF because RDN significantly reduces AF inducibility and shortens its duration.3. We also showed in our RI model that hypersympathetic activity may be involved directly in atrial electrophysiological changes and indirectly in the activation of RAAS, atrial inflammation, and fibrosis.