de Miranda Marcos Lopes, Pereira Sandra J, Santos Ana O M T, Villela Nivaldo R, Kraemer-Aguiar Luiz Guilherme, Bouskela Eliete
Department of Internal Medicine, Division of Critical Care, Faculty of Medical Sciences, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil.
Pediatric Cardiac Intensive Care Unit, Perinatal Barra, Rio de Janeiro, RJ, Brazil.
PLoS One. 2015 Feb 3;10(2):e0117004. doi: 10.1371/journal.pone.0117004. eCollection 2015.
Apart from its inotropic property, milrinone has vasodilator, anti-inflammatory and antithrombotic effects that could assist in the reversal of septic microcirculatory changes. This paper investigates the effects of milrinone on endotoxemia-related microcirculatory changes and compares them to those observed with the use of norepinephrine.
After skinfold chamber implantation procedures and endotoxemia induction by intravenous Escherichia coli lipopolysaccharide administration (2 mg.kg-1), male golden Syrian hamsters were treated with two regimens of intravenous milrinone (0.25 or 0.5 μg.kg-1.min-1). Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables. Macro-hemodynamic, biochemical, and hematological parameters and survival rate were also analyzed. Endotoxemic non-treated animals, endotoxemic animals treated with norepinephrine (0.2 μg.kg-1.min-1), and non-endotoxemic hamsters served as controls.
Milrinone (0.5 μg.kg-1.min-1) was effective in reducing lipopolysaccharide-induced arteriolar vasoconstriction, capillary perfusion deficits, and inflammatory response, and in increasing survival. Norepinephrine treated animals showed the best mean arterial pressure levels but the worst functional capillary density values among all endotoxemic groups.
Our data suggests that milrinone yielded protective effects on endotoxemic animals' microcirculation, showed anti-inflammatory properties, and improved survival. Norepinephrine did not recruit the microcirculation nor demonstrated anti-inflammatory effects.
米力农除具有正性肌力作用外,还具有血管舒张、抗炎和抗血栓作用,可能有助于逆转脓毒症时的微循环变化。本文研究米力农对内毒素血症相关微循环变化的影响,并将其与使用去甲肾上腺素时观察到的影响进行比较。
在植入皮褶小室并通过静脉注射大肠杆菌脂多糖(2mg·kg-1)诱导内毒素血症后,对雄性叙利亚金黄地鼠采用两种静脉注射米力农的方案进行治疗(0.25或0.5μg·kg-1·min-1)。通过对皮褶小室标本进行活体显微镜检查,对微血管变量进行定量分析。还分析了宏观血流动力学、生化和血液学参数以及存活率。未治疗的内毒素血症动物、用去甲肾上腺素(0.2μg·kg-1·min-1)治疗的内毒素血症动物以及非内毒素血症仓鼠作为对照。
米力农(0.5μg·kg-1·min-1)可有效减轻脂多糖诱导的小动脉血管收缩、毛细血管灌注不足和炎症反应,并提高存活率。在所有内毒素血症组中,去甲肾上腺素治疗的动物平均动脉压水平最佳,但功能性毛细血管密度值最差。
我们的数据表明,米力农对内毒素血症动物的微循环具有保护作用,具有抗炎特性,并能提高存活率。去甲肾上腺素未改善微循环,也未显示出抗炎作用。