Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits

Abstract

Levosimendan has a calcium-sensitizing effect in the myocardium and opens ATP-sensitive potassium channels (K_ATP) in vascular smooth muscle. Because airway smooth muscle also expresses K_ATP, we characterized the protective potential of levosimendan against increased airway and respiratory tissue resistances. Animals were administered levosimendan alone (<i>group L</i>), levosimendan after pretreatment with a K_ATP channel blocker (glibenclamide, <i>group LG</i>), glibenclamide only (<i>group G</i>), or solvent alone (dextrose, <i>group C</i>). Airway resistance (R_aw), tissue damping, and elastance were determined by forced oscillations under baseline conditions and following provocation tests with intravenous methacholine (MCh). Cardiac output (CO) was assessed by transpulmonary thermodilution. The same sequence of measurements was then repeated during intravenous infusion of levosimendan in <i>groups L</i> and <i>LG</i> or glucose in <i>groups G</i> and <i>C</i> Sham treatments in <i>groups C</i> and <i>G</i> had no effect on lung responsiveness. However, levosimendan treatment in <i>group L</i> elevated CO and inhibited the MCh-induced airway responses [R_aw changes of 87.8 ± 83% (SD) vs. 24.4 ± 16% at 4 μg·kg^-1·min^-1 MCh, <i>P</i> < 0.001], and in G (35.2 ± 12.7 vs. 25.2 ± 12.9%, <i>P</i> < 0.05). The preventive affect of levosimendan against lung constriction vanished in the LG group. Levosimendan exerts a K_ATP-mediated potential to prevent bronchoconstriction and may prohibit adverse lung peripheral changes both in the small bronchi and the pulmonary parenchyma. The identification of a further pleiotropic property of levosimendan that is related to the pulmonary system is of particular importance for patients with decreased cardiorespiratory reserves for which simultaneous circulatory support is complemented with prevention of adverse respiratory events.