Transmembrane ionic currents in atrial myocytes in sinus rhythm and chronic atrial fibrillation in human and animal models View Homepage


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2010-2014

FUNDING AMOUNT

13994000.0 HUF

ABSTRACT

We have developed a new tachypaced chronic atrial fibrillation dog model (ATR). In dog ATR atrial myocytes Ito slightly downregulated, while IK1 upregulated. We have reported the clear presence of a ligand independent constitutively activated IKACh current in the dog ATR cells, which plays an important role in the atrial remodelling. We have investigated the effects of a novel IKur blocker substance XEND010, and we have concluded that due to its selectively IKur blocking effects, possess a strong Class III atrial selective antiarrhythmic potency. We have reported that administration of extremely high concentration of diclofenac (as for top athletes) attenuated RR, which may increase proarrhythmic tendency. We have showed that the racemic R-L3 compound, ZS 1271B is a potent IKs activator, which make it suitable for testing the antiarrhythmic property of the IKs activator drugs. We have observed that the antianginal drugs ivabradine and ranolazine possess also strong use dependent Na-channel blocking properties. We have reported that the Ca activated K+ channels contributed importantly to cardiac repolarization remodelling. By testing the novel NCX blocker drug ORM-10103, we clearly demonstrated that NCX blockade indeed have strong antiarrhythmic effect. We have reported that repolarization reserve in human myocardium is less than that observed in the dog, ie., the proarrhythmic effect several cardiac drugs can be underestimated in human based on experiments performed in dog. More... »

URL

http://nyilvanos.otka-palyazat.hu/index.php?menuid=930&num=82079&lang=EN

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