Hemodynamic Effects of Late Sodium Current Inhibitors in a Swine Model of Heart Failure.

Objectives: To evaluate possible treatment-related hemodynamic changes, we administered ranolazine or mexiletine to swine with heart failure (HF) and to controls.

Background: Ranolazine and mexiletine potently inhibit depolarizing late Na current (I) and Na entry into cardiomyocytes Blocking Na entry may increase forward-mode Na/Ca exchange and reduce cellular Ca load, further compromising systolic contraction during HF.

Methods And Results: Anesthetized tachypaced HF swine received ranolazine (n = 9) or mexiletine (n = 7) as boluses, then as infusions; the same experiments were performed in 10 nonpaced controls.