Levosimendan Enhances Force Generation of Diaphragm Muscle from Patients with Chronic Obstructive Pulmonary Disease

Rationale: Levosimendan is clinically used to improve myocardial contractility by enhancing calcium sensitivity of force generation. The effects of levosimendan on skeletal muscle contractility are unknown. Patients with chronic obstructive pulmonary disease (COPD) suffer from diaphragm weakness, which is associated with decreased calcium sensitivity. Objectives: To investigate the effects of levosimendan on contrac-tility of diaphragm fibers from patients with COPD. Methods: Muscle fibers were isolated from diaphragm biopsies obtained from thoracotomized patients with and without COPD (both groups n 5 5, 10 fibers per patient). Diaphragm fibers were skinned and activated with solutions containing incremental cal-cium concentrations and 10 mM levosimendan or vehicle (0.02% dimethyl sulfoxide). Developed force was measured at each step and force versus calcium concentration relationships were derived