Hagiwara Satoshi, Iwasaka Hideo, Hasegawa Akira, Asai Nobuhiko, Noguchi Takayuki
Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi, Yufu City, Oita, Japan.
Crit Care Med. 2009 Jul;37(7):2223-7. doi: 10.1097/CCM.0b013e3181a007c6.
Hyperglycemia is frequently observed in nondiabetic patients during acute illness. Furthermore, intensive insulin therapy significantly reduces mortality and morbidity due to several critical illnesses, including cardiac or infectious diseases. The purpose of this study was to determine whether cardiac function is affected by hyperglycemia and its treatment with insulin.
Lipopolysaccharide (LPS) was administered intravenously to rats, with or without the administration of insulin with glucose.
University Medical Center research laboratory.
Male Wistar rats.
In this study, we determined the effect of hyperglycemia and insulin therapy on cardiac function in an LPS-induced systemic inflammation model.
Levels of serum cytokines, nitrate/nitrite, and high-mobility group box 1 protein after LPS treatment were measured in hyperglycemic rats and those treated with insulin. The following parameters were examined to assess cardiac function in Langendorff-perfused hearts: left ventricular developed pressure, left ventricular end-diastolic pressure, and left ventricular pressure development during isovolumetric contraction (+dP/dtmax) and relaxation (-dP/dtmin). We observed that levels of cytokines, nitrate/nitrite, and high-mobility group box 1 significantly increased. However, treatment of hyperglycemic rats with insulin was associated with significantly less severe disease as assessed by cytokine levels. Furthermore, hyperglycemia was associated with decreased +dP/dtmax and -dP/dtmin in Langendorff-perfused hearts of hyperglycemic rats, whereas insulin treatment improved these parameters.
Hyperglycemia was associated with the induction of various inflammatory mediators and an inhibition of cardiac function. Treatment of hyperglycemia with insulin protected against inflammation and cardiac dysfunction in a rat model of LPS-induced systemic inflammation. This improvement is likely because of the neutralization of deleterious effects associated with hyperglycemia and the specific actions of insulin on the inflammatory response.
在急性疾病期间，非糖尿病患者中经常观察到高血糖。此外，强化胰岛素治疗可显著降低包括心脏或感染性疾病在内的几种危重病的死亡率和发病率。本研究的目的是确定心脏功能是否受高血糖及其胰岛素治疗的影响。
对大鼠静脉注射脂多糖（LPS），同时或不同时给予胰岛素和葡萄糖。
大学医学中心研究实验室。
雄性Wistar大鼠。
在本研究中，我们在LPS诱导的全身炎症模型中确定了高血糖和胰岛素治疗对心脏功能的影响。
在高血糖大鼠和接受胰岛素治疗的大鼠中，测量LPS治疗后血清细胞因子、硝酸盐/亚硝酸盐和高迁移率族蛋白B1的水平。在Langendorff灌注心脏中检查以下参数以评估心脏功能：左心室舒张末压、左心室舒张末压力、等容收缩期左心室压力上升（+dP/dtmax）和舒张期左心室压力下降（-dP/dtmin）。我们观察到细胞因子、硝酸盐/亚硝酸盐和高迁移率族蛋白B1的水平显著升高。然而，根据细胞因子水平评估，用胰岛素治疗高血糖大鼠与疾病严重程度显著减轻相关。此外，高血糖与高血糖大鼠Langendorff灌注心脏中 +dP/dtmax和 -dP/dtmin降低有关，而胰岛素治疗改善了这些参数。
高血糖与多种炎症介质的诱导和心脏功能抑制有关。在LPS诱导的全身炎症大鼠模型中，用胰岛素治疗高血糖可预防炎症和心脏功能障碍。这种改善可能是由于中和了与高血糖相关的有害作用以及胰岛素对炎症反应的特定作用。
