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Ivabradine Affect Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel In Atrium With Age-Related Atrial Fibrillation Dog

Posted on:2017-03-01Degree:MasterType:Thesis
Country:ChinaCandidate:Y T JiFull Text:PDF
GTID:2284330485457692Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: To explore the effects of Ivabradine on the electrophysiological parameters,the expressions of HCN2 and HCN4 channels mRNAs and proteins levels in the pulmonary vein and atrial tissues in a dog model of age-related atrial fibrillation(AF), and investigate the underlying mechanisms. Methods: Through the external jugular vein to implantation of a pacemakert to generate rapid auricle pacing with the frequency to induce the age-related AF model 6 weeks, randomly divided into 2 groups after successful modeling. Experiment group was capsule Ivabradine 2 weeks. The effects of Ivabradine on the electrophysiological parameters(the induced rate of AF, the duration of AF after induction, effective refractory period of atrial tissues and pulmonary vein), the expressions of HCN2 and HCN4 channels mRNAs and proteins in the pulmonary vein and atrial tissues were measured by PCR and Western blot after two weeks. Observe the morphological changes of left atrial tissues in a dog model of age-related AF by HE staining and Masson staining. Results: Ivabradine could decrease the inducing rate of AF(25% vs 60%, P=0.001), reduce the duration of AF after induction(46.60±5.07 s VS205.40±1.14 s, P=0.001), increase the ERPs of the left superior pulmonary vein(139.00±4.18 ms VS 129.00±4.08 ms, P=0.005) and left atrial(135.00±3.53 ms VS122.00±4.47 ms, P=0.001). Also, the expressions of HCN2 and HCN4 channels mRNAs and proteins decreased significantly in the pulmonary vein and left atrial tissues(P<0.05)between two group. However, Ivabradine does not have an impact on morphology and the inside diameter of left atrial tissues in a dog model of age-related atrial fibrillation.Conclusion: Ivabradine could reduce the expression of HCN channels mRNAs and proteins in the pulmonary vein and atrial tissues of dogs with age-related AF, therebycould effectively reduce the inducing rate of AF. Thus be used as an upstream drug for the prevention of age-related AF.
Keywords/Search Tags:Atrial fibrillation, Ivarbadine, Funny current, Hyperpolarization-Activated Cyclic Nucleotide-Gated channel, Aging
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