Effects Of Renal Impairment On Blood Coagulation And Endothelial Function Of Atrial Fibrillation In Canines

Background and ObjectivesThe incidence of atrial fibrillation(AF) increased with the age. Stroke was the most common and severe complications of AF, and nearly 20% of stroke caused by AF. In contrast with patients without AF, patients with AF increased the risk of stroke by 4～5 times. Recently, the incidence of chronic renal impairment (RI) increased significantly and RI could raise the risk of thrombosis and bleeding. The incidence of AF complicated with RI also increased significantly, and there was no universal standard for scoring and monitoring on anticoagulant of patients with AF and RI. The main purpose of this study is to observe the effects of RI on blood coagulation and endothelial function of AF through animal experiment. This study has important implications for understand the changes of blood coagulation and endothelial function in patients with AF and RI, and it will provide references for anticoagulant therapy of the population that AF combined with RI.MethodsPart One:Animals were randomly divided into model group (n=10), pacing group (n=5) and blank control group (n=5). Acute RI was induced in beagles by embolization of unilateral main renal artery for 1 month using gelatin sponge granules in the model group. The pacing group and 5 beagles of model group were stimulated right atrium for 3 hours rapidly to establish AF model. The parameters associated with renal function and RI were tested and cardiac electrophysiological parameters, AF vulnerability were investigated in the model group with means of before-after contrast. Parameters associated with endothelial function and blood coagulation, the activity of renin-angiotensin-aldosterone system (RAAS), inflammation and oxidative stress were measured in the model group and the pacing group.Part Two:Animals were randomly divided into model group (n=10), pacing group (n=5) and blank control group (n=5). The pacing group and the control group were as same as the part one. Chronic RI was induced in beagles by embolization of unilateral main renal artery for 3 month using gelatin sponge granules in the model group. The pacing group and 5 beagles of model group were stimulated right atrium for 3 hours rapidly to establish AF model. The parameters associated with renal function and RI were tested and cardiac electrophysiological parameters, AF vulnerability were investigated in the model group with means of before-after contrast. Parameters associated with endothelial function and coagulation, the activity of RAAS, inflammation, and oxidative stress were measured in the model group and the pacing group.ResultsPart One:Embolization of unilateral main renal artery for 1 month led to acute ischemic RI with moderate renal insufficiency. The AF model were established successfully. The following changes were investigated after embolization and stimulation. (1) The antegrade Wenkebach point and the atrial effective refractory period (AERP) were shortened. (2) The inducibility of AF increased. (3) Compared with the pacing group, endothelial dysfunction of acute RI with AF were soft, procoagulant substances decreased, fibrinolysis activity increased, the activity of inflammation and oxidative stress decreased.Part Two:Embolization of unilateral main renal artery for 3 months led to chronic ischemic RI with moderate renal insufficiency. The following changes were investigated after embolization and stimulation. (1) The antegrade Wenkebach point and the AERP were shortened. (2) The inducibility of AF increased. (3) Compared with the pacing group, endothelial dysfunction of chronic RI with AF were severe, procoagulant substances increased, fibrinolysis activity decreased, the activity of inflammation strengthened, RAAS were activated. (4) Compared with acute RI with AF, endothelial dysfunction of chronic RI with AF were severe, procoagulant substances increased, fibrinolysis activity decreased, the activity of inflammation and oxidative stress strengthened, RAAS were activated.Conclusions1. We established in vivo model of acute and chronic RI with moderate renal insufficiency in a large animal and then established AF model successfully.2. Using these models, we showed that endothelial dysfunction in acute moderate renal insufficiency complicated with AF were soft, the risk of bleeding increased, the risk of thrombosis decreased.3. Endothelial dysfunction in chronic moderate renal insufficiency with AF were severe, the risk of thrombosis increased, the risk of bleeding decreased.