White Jean, Thomas James, Maass David L, Horton Jureta W
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390-9160, USA.
Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H47-58. doi: 10.1152/ajpheart.00833.2002. Epub 2003 Mar 13.
Early fluid resuscitation, antimicrobials, early excision, and grafting have improved survival in the early postburn period; however, a significant incidence of pneumonia-related sepsis occurs after burn injury, often progressing to multiple organ failure. Recent studies have suggested that this initial injury (burn injury) primes the subject, producing an exaggerated response to a second insult, such as pneumonia-related sepsis. We developed an experimental animal model that included a third-degree burn over 40% of the total body surface area, followed by sepsis (intratracheal administration of Streptococcus pneumoniae, 4 x 106 colony-forming unit), which was produced either 48 or 72 h after burn injury in adult male rats. Hearts harvested after either burn alone, sepsis alone, or burn plus sepsis were used to assess either contractile function (Langendorff) or cardiomyocyte secretion of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-10 (ELISA). Experimental groups included the following: 1). sham (sham burn and no sepsis); 2). burn injury alone studied either 24, 48, or 72 h postburn; 3). pneumonia-related sepsis in the absence of burn injury; and 4). pneumonia-induced sepsis studied either 48 or 72 h after an initial burn injury. Burn injury alone (24 h) or sepsis alone produced myocardial contractile defects and increases in pro- and anti-inflammatory cytokine secretion by cardiomyocytes. Sepsis that occurred 48 h postburn exacerbated the cardiac contractile defects seen with either burn alone or sepsis alone. Sepsis that occurred 72 h postburn produced contractile defects resembling those seen in either burn alone or sepsis alone. In conclusion, our data suggest that burn injury primes the subject such that a second insult early in the postburn period produces significantly greater cardiac abnormalities than those seen with either burn alone or sepsis alone.
早期液体复苏、使用抗菌药物、早期切除和植皮改善了烧伤后早期的生存率;然而,烧伤后与肺炎相关的脓毒症发生率很高,常进展为多器官功能衰竭。最近的研究表明,这种初始损伤(烧伤)使机体致敏,对第二次损伤(如与肺炎相关的脓毒症)产生过度反应。我们建立了一种实验动物模型,对成年雄性大鼠造成占全身表面积40%的三度烧伤,随后在烧伤后48或72小时通过气管内注射肺炎链球菌(4×106菌落形成单位)诱导脓毒症。分别在单纯烧伤、单纯脓毒症或烧伤加脓毒症后采集心脏,用于评估收缩功能(Langendorff法)或心肌细胞分泌肿瘤坏死因子-α、白细胞介素(IL)-1β、IL-6和IL-10(酶联免疫吸附测定法)。实验组包括以下几组:1).假手术组(假烧伤且无脓毒症);2).单纯烧伤组,分别在烧伤后24、48或72小时进行研究;3).无烧伤损伤的肺炎相关脓毒症组;4).初次烧伤后48或72小时的肺炎诱导脓毒症组。单纯烧伤(24小时)或单纯脓毒症会导致心肌收缩功能缺陷,并增加心肌细胞促炎和抗炎细胞因子的分泌。烧伤后48小时发生的脓毒症会加剧单纯烧伤或单纯脓毒症时出现的心脏收缩功能缺陷。烧伤后72小时发生的脓毒症产生的收缩功能缺陷与单纯烧伤或单纯脓毒症时相似。总之,我们的数据表明,烧伤使机体致敏,因此在烧伤后早期的第二次损伤会产生比单纯烧伤或单纯脓毒症时明显更严重的心脏异常。