Melatonin improves survival and functional impairment including hemolysis, thrombocytopenia, and hypotension when administered in a prophylactic manner or early after initiation of sepsis or endotoxemia. In the present study, melatonin was given not before first symptoms of systemic inflammation became manifest. Lipopolysaccharide was infused at a rate of 0.5 mg/kg × h to induce systemic inflammation in male Wistar rats. Melatonin (single dose 3 mg/kg × 15 min) was intravenously administered 180 and 270 min after starting of the lipopolysaccharide infusion. Systemic and vital parameters (e.g., systemic blood pressure and breathing rate) as well as blood and plasma parameters (acid-base parameters; electrolytes; parameters of tissue injury such as glucose concentration, lactate concentration, hemolysis, and aminotransferase activities; parameters of thromboelastometry; and platelet count) were determined in regular intervals. Infusion of lipopolysaccharide led to characteristic symptoms of severe systemic inflammation including hypotension, metabolic acidosis and hypoglycemia, electrolyte and hemostatic disturbances, thrombocytopenia, and hemolysis. Melatonin neither decreased mortality nor reduced lipopolysaccharide-dependent changes to vital, blood, and plasma parameters. Even though melatonin may have a beneficial effect in early stages of systemic inflammation, it can hardly be an option in therapy of manifest sepsis or endotoxemia in an intensive care unit.

译文

褪黑素以预防性方式或在脓毒症或内毒素血症开始后的早期给药,可改善生存和功能障碍,包括溶血,血小板减少和低血压。在本研究中,褪黑激素未在系统性炎症的最初症状显现之前就给予。以0.5 mg / kg×h的速度注入脂多糖以诱导雄性Wistar大鼠全身性炎症。开始注入脂多糖后180和270分钟静脉注射褪黑激素(单次剂量3 mg / kg×15分钟)。全身和生命参数(例如全身血压和呼吸频率)以及血液和血浆参数(酸碱参数;电解质;组织损伤参数,例如葡萄糖浓度,乳酸浓度,溶血和转氨酶活性;血栓弹力测定法参数;以及血小板计数)是定期确定的。输注脂多糖会导致严重的全身性炎症,包括低血压,代谢性酸中毒和低血糖,电解质和止血失调,血小板减少和溶血。褪黑激素既不能降低死亡率,也不能降低脂多糖依赖性的生命,血液和血浆参数变化。即使褪黑激素在全身性炎症的早期阶段可能具有有益的作用,但在重症监护病房治疗明显的败血症或内毒素血症时,它几乎不是一种选择。

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