Experimental Hyperlipidemia Causes an Increase in the Electrocardiographic Changes Associated With Amiodarone

To assess the influence of hyperlipidemia (HL) on amiodarone (AM) effect in the heart, rats were pretreated with either 1 g/kg poloxamer 407 (to induce HL) or saline intraperitoneally. At approximately 36 hours afterward, rats were given AM HCl (25, 50, and 100 mg.kg.d) or saline intravenously through implanted venous cannulas for 5 days. Under anesthesia, electrocardiogram (ECG) was recorded using subcutaneous electrodes and blood samples were withdrawn at baseline and 12 hours after the first, middle, and last doses. At the end of the study, heart tissues were collected. Specimens were analyzed for AM and desethylamiodarone. HL by itself did not alter the ECG. Compared with baseline, the end of study prolongation of QTc and PR intervals were significantly (P < 0.05) higher in all AM-treated HL rats. AM plasma and heart concentrations in HL rats after the last dose were significantly (P < 0.05) higher than in normolipidemic rats. Similar to AM, in HL rats, plasma desethylamiodarone after the last dose was significantly higher than in normolipidemic rats. The cholesterol to triglyceride plasma ratio was linearly related to QT interval and plasma and heart AM concentrations. HL increased the ECG effects of AM by increasing heart concentrations.