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  • Title: Ivabradine but not propranolol delays the time to onset of ischaemia-induced ventricular fibrillation by preserving myocardial metabolic energy status.
    Author: Vaillant F, Dehina L, Dizerens N, Bui-Xuan B, Tabib A, Lauzier B, Chevalier P, Descotes J, Timour Q.
    Journal: Resuscitation; 2013 Mar; 84(3):384-90. PubMed ID: 22940600.
    Abstract:
    OBJECTIVE: Heart rate reduction (HRR) has shown a beneficial impact on the prevention of ventricular fibrillation, which could be explained by increased myocardial blood flow and preservation of mitochondrial structure. Here, we assessed the HRR impact on time to onset of ventricular fibrillation (TOVF) and myocardial metabolic energy status. METHODS AND RESULTS: An acute myocardial ischaemia was induced in pigs until ventricular fibrillation onset and TOVF was then measured. High-energy phosphates were measured in ventricular samples from the ischaemic region by nuclear magnetic resonance. Saline, ivabradine (IVA, a selective heart rate-lowering agent) and propranolol (PROPRA, a β-blocker) were administered intravenously, 30 and 60 min respectively prior to ischaemia to ensure stable HRR. To study specifically the HRR impact, another set of animals received IVA and was submitted to rapid atrial pacing (200 bpm) to abolish HRR. IVA and PROPRA induced a similar HRR (IVA: 22-26%, PRORA: 20-21%, p<0.01 vs. control), which was associated with a significant increase in TOVF with IVA (2325s) compared to PROPRA (682s) and saline (401s). This effect was abolished by atrial pacing performed during ischaemia and throughout the entire experimental session. Only IVA partially prevented the decrease in phosphocreatine-to-ATP ratio (CrP/ATP) ratio and the ADP accumulation at the onset of ventricular fibrillation. Finally, CrP/ATP ratio levels were correlated with TOVF (r=0.74, p<0.001). CONCLUSION: Unlike PROPRA, IVA delayed the time to onset of ischaemia-induced ventricular fibrillation by preserving myocardial energy status, supporting the pertinence of IVA in the management of patients with coronary artery disease.
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