Levosimendan Prevents Pressure-Overload-induced Right Ventricular Failure.

Abstract

We investigated if chronic levosimendan treatment can prevent and revert pressure-overload-induced right ventricular hypertrophy and failure in rats. Right ventricular hypertrophy and failure was induced in Wistar rats by pulmonary trunk banding (PTB). The PTB rats were treated with levosimendan (3 mg·kg·d) 3 days before surgery [n = 10, prevention (PREV)], 3 weeks after surgery [n = 10, reversal (REV)] or vehicle (n = 10, VEH). Sham-operated rats received vehicle (n = 16, SHAM). Right ventricular function was evaluated 7 weeks after surgery by echocardiography, magnetic resonance imaging, pressure-volume relations, gross anatomy, and histology. PTB induced right ventricular hypertrophy and compensated heart failure evident by reduced cardiac index (CI) without extra cardiac signs of heart failure. Levosimendan treatment prevented deterioration of right ventricular function measured by CI and right ventricular ejection fraction (RVEF) (CI: VEH vs. PREV 281 ± 17 vs. 362 ± 34 mL·min·kg, P ≤ 0.05, RVEF: VEH vs. PREV 57 ± 2% vs. 68 ± 3%, P ≤ 0.01) to values similar to SHAM (CI: 345 ± 21 mL·min·kg, RVEF: 71 ± 2%). RV contractility was improved in the REV group measured by preload recruitable stroke work (VEH vs. REV 39 ± 3 vs. 66 ± 10 mmHg P ≤ 0.05). Chronic treatment with levosimendan prevents the development of right ventricular failure and improves contractility in established pressure-overload-induced right ventricular failure.