Chen Lan, Liu Chang, Zhang Zhaocai, Zhang Yuping, Feng Xiuqin
Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, Zhejiang, China.
Department of Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
J Intensive Care. 2024 Oct 8;12(1):39. doi: 10.1186/s40560-024-00746-y.
Heatstroke is a life-threatening condition characterized by severe hyperthermia and multiple organ dysfunction. Both normal saline (NS) and lactated Ringer's solution (LR) are commonly used for cooling and volume resuscitation in heatstroke patients; however, their specific impacts on patient outcomes during heatstroke management are poorly understood. Given that the systemic inflammatory response and multiple-organ damage caused by heat toxicity are the main pathophysiological features of heatstroke, the aim of this study was to evaluate the effects of NS and LR on the production of inflammatory cytokines and the functional and structural integrity of renal and cardiac tissues in a rat model of heatstroke.
Fifty-five male Sprague‒Dawley rats were randomly divided into four groups: cold NS or LR infusion postheatstroke (4 ℃, 4 ml/100 g, over 10 min) and NS or LR infusion without heatstroke induction (control groups). Vital signs, arterial blood gases, inflammatory cytokines, and renal and cardiac function indicators, such as serum creatinine and cTnI, were monitored after treatment. Tissue samples were analysed via HE staining, electron microscopy, and fluorescence staining for apoptosis markers, and protein lysates were used for Western blotting of pyroptosis-related proteins.
Compared with LR-treated heatstroke rats, NS-treated heatstroke rats presented lower mean arterial pressures, worsened metabolic acidosis, and higher levels of IL-6 and TNF-α in both the serum and tissue. These rats also presented increased serum creatinine, troponin, catecholamines, and NGAL and reduced renal clearance. Histological and ultrastructural analyses revealed more severe tissue damage in NS-treated rats, with increased apoptosis and increased expression of NLRP3/caspase-1/GSDMD signalling molecules. Similar differences were not observed between the control groups receiving either NS or LR infusion. One NS-treated heatstroke rat died within 24 h, whereas all the LR-treated and control rats survived.
NS resuscitation in heat-exposed rats significantly promotes metabolic acidosis and the inflammatory response, leading to greater functional and structural organ damage than does LR. These findings underscore the necessity of selecting appropriate resuscitation fluids for heatstroke management to minimize organ damage and improve outcomes.
中暑是一种危及生命的病症,其特征为严重体温过高和多器官功能障碍。生理盐水(NS)和乳酸林格氏液(LR)通常都用于中暑患者的降温及容量复苏;然而,在中暑治疗过程中它们对患者预后的具体影响却鲜为人知。鉴于热毒性引起的全身炎症反应和多器官损伤是中暑的主要病理生理特征,本研究旨在评估NS和LR对中暑大鼠模型中炎症细胞因子产生以及肾和心脏组织功能与结构完整性的影响。
55只雄性Sprague-Dawley大鼠被随机分为四组:中暑后输注冷NS或LR(4℃,4ml/100g,超过10分钟)以及未诱导中暑而输注NS或LR的对照组。治疗后监测生命体征、动脉血气、炎症细胞因子以及肾和心脏功能指标,如血清肌酐和肌钙蛋白I(cTnI)。通过苏木精-伊红(HE)染色、电子显微镜检查以及凋亡标志物的荧光染色对组织样本进行分析,并且蛋白质裂解物用于焦亡相关蛋白的蛋白质印迹分析。
与接受LR治疗的中暑大鼠相比,接受NS治疗的中暑大鼠平均动脉压更低、代谢性酸中毒更严重,血清和组织中的白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平更高。这些大鼠血清肌酐、肌钙蛋白、儿茶酚胺和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)也升高,肾清除率降低。组织学和超微结构分析显示接受NS治疗的大鼠组织损伤更严重,凋亡增加,NLRP3/半胱天冬酶-1/GSDMD信号分子表达增加。在接受NS或LR输注的对照组之间未观察到类似差异。一只接受NS治疗的中暑大鼠在24小时内死亡,而所有接受LR治疗的大鼠和对照组大鼠均存活。
热暴露大鼠接受NS复苏显著促进代谢性酸中毒和炎症反应,导致比LR更大的器官功能和结构损伤。这些发现强调了为中暑治疗选择合适的复苏液以尽量减少器官损伤并改善预后的必要性。