Babik Barna, Balogh Adam L, Sudy Roberta, Ivankovitsne-Kiss Orsolya, Fodor Gergely H, Petak Ferenc
Department of Anesthesiology and Intensive Therapy, University of Szeged, Szeged, Hungary; and.
Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary.
Am J Physiol Lung Cell Mol Physiol. 2017 Nov 1;313(5):L950-L956. doi: 10.1152/ajplung.00213.2017. Epub 2017 Aug 24.
Levosimendan has a calcium-sensitizing effect in the myocardium and opens ATP-sensitive potassium channels (K) in vascular smooth muscle. Because airway smooth muscle also expresses K, we characterized the protective potential of levosimendan against increased airway and respiratory tissue resistances. Animals were administered levosimendan alone (), levosimendan after pretreatment with a K channel blocker (glibenclamide, ), glibenclamide only (), or solvent alone (dextrose, ). Airway resistance (R), 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 and or glucose in and Sham treatments in and had no effect on lung responsiveness. However, levosimendan treatment in elevated CO and inhibited the MCh-induced airway responses [R changes of 87.8 ± 83% (SD) vs. 24.4 ± 16% at 4 μg·kg·min MCh, < 0.001], and in G (35.2 ± 12.7 vs. 25.2 ± 12.9%, < 0.05). The preventive affect of levosimendan against lung constriction vanished in the LG group. Levosimendan exerts a K-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.
左西孟旦对心肌有钙增敏作用，并能开放血管平滑肌中的ATP敏感性钾通道（K）。由于气道平滑肌也表达K，我们研究了左西孟旦对气道和呼吸组织阻力增加的保护作用。给动物单独给予左西孟旦（）、用钾通道阻滞剂（格列本脲，）预处理后给予左西孟旦、仅给予格列本脲（）或仅给予溶剂（葡萄糖，）。在基线条件下以及静脉注射乙酰甲胆碱（MCh）激发试验后，通过强迫振荡测定气道阻力（R）、组织阻尼和弹性。通过经肺热稀释法评估心输出量（CO）。然后在静脉输注左西孟旦的过程中，对和重复相同的测量序列，在和中输注葡萄糖。和中的假处理对肺反应性没有影响。然而，中的左西孟旦治疗提高了CO，并抑制了MCh诱导的气道反应[在4μg·kg·min MCh时，R变化为87.8±83%（标准差）对24.4±16%，<0.001]，在G组中为（35.2±12.7对25.2±12.9%，<0.05）。左西孟旦对肺收缩的预防作用在LG组中消失。左西孟旦发挥钾介导的预防支气管收缩的作用，并可能阻止小支气管和肺实质中不良的肺外周变化。确定左西孟旦与肺系统相关的另一种多效性特性，对于心肺储备降低且需要同时进行循环支持和预防不良呼吸事件的患者尤为重要。
