Role of Lipids and Lipid Metabolites in Myocardial Ischaemia

Ranolazine:an Antiischemic Drug with a Novel Mechanism of Action

“…In a double-blind, crossover, and randomized study, Cocco et al (16) examined the effect of a single oral administration of ranolazine (10,60,120, or 240 mg) on exercise tolerance in 104 patients who had chronic stable angina and still remained symptomatic despite treatment with a ␤-adrenoceptor antagonist or diltiazem. Their study revealed that ranolazine at a dose of 240 mg improved the duration of exercise and time to 1 mm of ST segment depression, whereas lower doses of ranolazine (30,60, and 120 mg) had no significant effects. Thadani et al (62) reported that low doses of ranolazine (30,60, and 120 mg) failed to produce the antianginal action, even when patients were treated orally with the drug t.i.d.…”

“…Their study revealed that ranolazine at a dose of 240 mg improved the duration of exercise and time to 1 mm of ST segment depression, whereas lower doses of ranolazine (30,60, and 120 mg) had no significant effects. Thadani et al (62) reported that low doses of ranolazine (30,60, and 120 mg) failed to produce the antianginal action, even when patients were treated orally with the drug t.i.d. for 4 w. In another double-blind, crossover, and randomized study, Rousseau et al (54) reported that oral administration of ranolazine (342 mg, t.i.d.)…”

“…Therefore, a shift in the substrate from fatty acids to carbohydrates in the myocardium may be one of the major mechanisms of the antiischemic action of CPT I inhibitors. It should be noted, however, that inhibition of CPT I reduces the ischemia-induced tissue accumulation of long-chain acylcarnitines, which leads to ischemic damage (18,19,60). Therefore, the effect of CPT I inhibitors in reducing the tissue accumulation of long-chain acylcarnitines may also contribute to its antiischemic action (17).…”