(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Arrhythmias--Cardiac

To investigate the effect of fluvastatin on lysophosphatidylcholine (LPC)-induced ventricular arrhythmias and its mechanism.. Twenty male SD rats were randomly allocated into two equal groups, namely LPC treatment group and fluvastatin pretreatment group. Langendorff apparatus was used for cardiac perfusion ex vivo with 5 µmol/L LPC for 5 min followed by washing for 30 min in LPC treatment group, and in fluvastatin pretreatment group, a 30-min perfusion with 10 µmol/L fluvastatin was administered before LPC perfusion. The LPC-induced nonselective cation current (I(NSC)) in the ventricular myocytes was recorded using the whole-cell voltage-clamp method.. Fluvastatin significantly inhibited LPC-induced ventricular tachyarrhythmia/fibrillation and I(NSC). The small G-protein Rho inhibitor (C3) and Rho-kinase inhibitor (Y-27632) in the pipette solution also suppressed LPC-induced I(NSC).. Fluvastatin offers cardiac protection against LPC by inhibiting LPC-induced I(NSC). LPC induces fatal arrhythmia via a Rho/Rho-kinase-mediated pathway.

Topics: Animals; Arrhythmias, Cardiac; Drug Antagonism; Fatty Acids, Monounsaturated; Fluvastatin; Indoles; Ion Channels; Lysophosphatidylcholines; Male; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; rho-Associated Kinases

We have reported that chronically administered pravastatin prevented coronary artery reperfusion-induced lethal ventricular fibrillation (VF) in anesthetized rats without lowering the serum cholesterol level. The present study was undertaken to evaluate whether pravastatin prevents ischemia-induced lethal VF, simultaneously examining myeloperoxidase (MPO) activity in ischemic myocardial tissues. Anesthetized rats were subjected to 30-min ischemia and 60-min reperfusion after chronic administration of pravastatin (0.02, 0.2, and 2 mg/kg), fluvastatin (2 and 4 mg/kg), or vehicle for 22 days, orally, once daily. ECG and blood pressure were continually recorded, and MPO was measured by a spectrophotometer. Pravastatin and fluvastatin significantly (P<0.05) decreased MPO activities, but only pravastatin decreased the incidence of ischemia-induced lethal VF. Both statins had no significant effects on body weight, blood pressure, heart rate, and QT interval as we reported earlier. Our results prove further that pravastatin has benefits to decrease cardiovascular mortality beyond its cholesterol-lowering effect. Pravastatin is more potent than fluvastatin in prevention of arrhythmias. A decrease in the neutrophil infiltration may be partly involved in the inhibitory effect of pravastatin on the ischemia-induced VF.

Topics: Administration, Oral; Anesthesia; Animals; Arrhythmias, Cardiac; Coronary Vessels; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatty Acids, Monounsaturated; Fluvastatin; Hydroxymethylglutaryl CoA Reductases; Indoles; Ischemia; Male; Peroxidase; Pravastatin; Rats; Rats, Sprague-Dawley

Topics: Arrhythmias, Cardiac; Coronary Disease; Electrocardiography; Fatty Acids, Monounsaturated; Fluvastatin; Heart Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Indoles; Lipids; Middle Aged; Treatment Outcome