Ivabradine induces an increase in ventricular fibrillation threshold during acute myocardial ischemia: an experimental study.
BACKGROUND
Tachycardia often facilitates ischemic ventricular fibrillation (VF).


OBJECTIVE
This study assessed the impact of ivabradine (IVA), a selective inhibitor of the cardiac pacemaker If current, on ventricular fibrillation threshold (VFT) during acute myocardial ischemia.


METHODS
The experiments were conducted on a total of 54 domestic pigs. Myocardial ischemia was induced in anesthetized pigs by total 1-minute coronary occlusion at baseline and then on 2 occasions after intravenous administration of saline or 0.5 mg/kg of IVA. VF was triggered by electrical stimuli of increasing intensity at a fixed rate. Heart rate (HR), VFT, monophasic action potential duration, and peak of the time derivative of left ventricular pressure (LV dP/dt max) were monitored on each occasion. The activity of mitochondrial succinodehydrogenase was measured on heart sections.


RESULTS
Compared with controls, IVA induced a 31% reduction in HR, a 2.9-fold increase in VFT, and prevented ischemia-induced monophasic action potential duration shortening (+1 +/- 12 vs. -14 +/- 11 milliseconds) without affecting peak LV dP/dt. This beneficial effect on VFT was mainly due to HR reduction and was accompanied by a significant reduction in the hypoxic area (26% +/- 1% vs. 38% +/- 1%, P < 0.0001).


CONCLUSIONS
HR reduction and the decrease in myocardial damage induced by IVA protected against primary ischemic VF without altering myocardial contractility.
Vaillant
Fanny
F
Laboratory of Medical Pharmacology, INSERM ERI 22, Grange Blanche Medical School, Claude Bernard University, Lyon, France.
Timour
Quadiri
Q
Descotes
Jacques
J
Manati
Waheed
W
Belhani
Dalila
D
Bui-Xuan
Bernard
B
Tabib
Alain
A
Bricca
Giampiero
G
Chevalier
Philippe
P
D000200:Action Potentials; D000208:Acute Disease; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D000077550:Ivabradine; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013385:Succinate Dehydrogenase / Q000378:metabolism; D034421:Sus scrofa; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D000077550:Ivabradine; D013385:Succinate Dehydrogenase