Protective effect of fenofibrate against ischemia-/reperfusion-induced cardiac arrhythmias in isolated rat hearts.

Autor: Bukhari IA; Department of Pharmacology, College of Medicine, King Saud University P. O. BOX 2454, Riyadh, 11451, Saudi Arabia., Almotrefi AA; Department of Pharmacology, College of Medicine, King Saud University P. O. BOX 2454, Riyadh, 11451, Saudi Arabia., Mohamed OY; Department of Pharmacology, College of Medicine, King Saud University P. O. BOX 2454, Riyadh, 11451, Saudi Arabia., Al-Masri AA; Department of Physiology, Cardiovascular Research Group, College of Medicine, King Saud University P. O. BOX 2454, Riyadh, 11451, Saudi Arabia., Sheikh SA; Department of Pharmacology, College of Medicine, King Saud University P. O. BOX 2454, Riyadh, 11451, Saudi Arabia.
Jazyk: angličtina
Zdroj: Fundamental & clinical pharmacology [Fundam Clin Pharmacol] 2018 Apr; Vol. 32 (2), pp. 141-146. Date of Electronic Publication: 2018 Jan 25.
DOI: 10.1111/fcp.12342
Abstrakt: Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α activator that lowers triglycerides and influences cytochrome P-450 (CYP-450) epoxygenase-dependent arachidonic acid (AA) metabolism. CYP-450 epoxygenase metabolizes AA to epoxyeicosatrienoic acids (EETs). EETs have coronary dilating and cardiac and renal protective properties. Fibrates possess similar properties due to their CYP-450 epoxygenase-inducing properties that lead to increase in endogenous EET production. In the current investigations, fenofibrate (100 mg/kg, orally) for 2 weeks decreased ischemia-/reperfusion (I/R)-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) in the isolated rat hearts. Fenofibrate caused marked inhibition of the reperfusion-induced cardiac arrhythmias. The incidence of reperfusion-induced VF decreased from 80% in the control vehicle-treated animals to 33% in the fenofibrate-treated animals (P < 0.001). PVCs were also significantly (P < 0.01) decreased from 223.2 ± 51 in control vehicle-treated animals to 136.8 ± 22 in fenofibrate-treated animals. Total duration of reperfusion-induced VT decreased from 29.2 ± 6.3 s in control, vehicle-treated animals to 4.8 ± 1.3 s in fenofibrate-treated animals, P < 0.001. Heart rate and perfusion pressure were not significantly affected by fenofibrate pretreatment. Diltiazem, a clinically used anti-arrhythmic agent, produced complete protection against I/R-induced cardiac arrhythmias in this model reducing the incidence of VF from 80% in control, vehicle-treated animals to 10% in diltiazem-treated hearts. These findings indicate that fenofibrate suppresses arrhythmias in isolated rat hearts subjected to I/R-induced injury.
(© 2017 Société Française de Pharmacologie et de Thérapeutique.)
Databáze: MEDLINE
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