Skip to Main content Skip to Navigation
Theses

Impact fonctionnel et métabolique d’une réduction de la fréquence cardiaque induite par un inhibiteur du courant If, l’ivabradine : approche expérimentale chez le porc et la souris

Abstract : Ischemic cardiopathies are a major cause of cardiovascular mortality potentially leading tosudden death by ventricular fibrillation (VF). In patients with coronary disease, onetherapeutic goal is to reduce oxygen requirements via slowing of heart rate (SHR). Severalmedicinal drugs, such as beta-blockers and calcium inhibitors can achieve this goal, but canresult in altered cardiac contractility and various adverse effects, which restricts their use. Wefocused our interest on the effects of a selective inhibitor of the pacemaker current If, namelyivabradine (IVA), which can reduce sinusal heart rate. The aim of the present work was toevaluate the impact of SHR on the propensity to VF and to better understand thephysiological and metabolism mechanisms involved. The first study was performed on a pigmodel of acute myocardial ischemia leading to VF. In the second study, the impact of SHRwas evaluated using a mouse model of isolated perfused working heart. Our resultsdemonstrated that IVA induced SHR in both models and this was associated in vivo withenhanced coronary flow, conservation of mitochondrial structure and myocardial energeticstatus, thus reducing the risk of triggering ischemia-induced VF. Moreover, ex vivo, theobserved SHR did not change the selection of substrates for energy production. From atherapeutic point of view, it is critical to improve the conditions within tissues and to reducethe loss of substrates during myocardial ischemia. IVA apparently met this goal. Indeed, viaspecific effects on sinusal automaticity, it can act both preventively and curatively
Document type :
Theses
Complete list of metadatas

Cited literature [242 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-00817208
Contributor : Abes Star :  Contact
Submitted on : Wednesday, April 24, 2013 - 9:57:12 AM
Last modification on : Wednesday, November 20, 2019 - 3:05:04 AM
Long-term archiving on: : Thursday, July 25, 2013 - 4:11:38 AM

File

TH2010_Vaillant_-_Fanny.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-00817208, version 1

Collections

Citation

Fanny Vaillant. Impact fonctionnel et métabolique d’une réduction de la fréquence cardiaque induite par un inhibiteur du courant If, l’ivabradine : approche expérimentale chez le porc et la souris. Médecine humaine et pathologie. Université Claude Bernard - Lyon I, 2010. Français. ⟨NNT : 2010LYO10225⟩. ⟨tel-00817208⟩

Share

Metrics

Record views

474

Files downloads

1402