Merchant Sanah, Nadaraj Sumekala, Chowdhury Devyani, Parnell Vincent A, Sison Cristina, Miller Edmund J, Ojamaa Kaie
Department of Pediatrics, Schneider Choldren's Hospital, New Hyde Park, New York, USA.
Mol Med. 2008 Mar-Apr;14(3-4):124-30. doi: 10.2119/2007-00086.Merchant.
Macrophage migration inhibitory factor (MIF), a proinflammatory mediator, has been shown to be elevated following heart surgery in adults and may be associated with several postoperative complications, including cardiac and pulmonary dysfunction. In this study, we aimed to measure perioperative plasma MIF, interleukin (IL)-8, and free T4 in 20 children age <4 years undergoing surgical repair of congenital heart lesions with left ventricular volume overload, and to determine whether the response of these mediators determined postoperative outcomes. Plasma samples were obtained preoperatively, immediately on arrival in the pediatric intensive care unit (PICU), and at 12, 24, and 48 h. Patients were continuously monitored in the PICU, and data were recorded daily for therapeutic and monitoring procedures that reflected the invasiveness, intensity, and complexity of care rendered (therapeutic interventional scoring system, TISS). Preoperative plasma MIF, IL-8, and free T4 were not different from age-matched healthy children. However, plasma MIF and IL-8 increased significantly 2 h after completion of cardiopulmonary bypass, and then normalized within 24 h. Peak postoperative levels of MIF (48 +/- 24 ng/mL) and IL-8 (79 +/- 57 pg/mL) correlated significantly with duration of cardiopulmonary bypass. The magnitude of the postoperative increase in plasma MIF was associated with increased number of days required for mechanical ventilation (r = 0.553; P = 0.012), and peak plasma IL-8 correlated significantly with the fraction of inhaled oxygen (FiO(2)) required immediately after surgery (r = 0.510; P = 0.02). Higher circulating MIF levels correlated significantly with increased inotropic support requirements on the second postoperative day, whereas higher postoperative IL-8 levels were associated with higher TISS scores, suggesting increased need for postoperative medical care. These data suggest a potential negative effect of high circulating levels of MIF in the immediate postoperative period on respiratory and cardiovascular functions, and support the development of therapeutic strategies targeting MIF function in this clinical setting.
巨噬细胞移动抑制因子(MIF)是一种促炎介质,研究表明,成人心脏手术后其水平会升高,且可能与多种术后并发症相关,包括心脏和肺功能障碍。在本研究中,我们旨在检测20名年龄小于4岁、因左心室容量超负荷接受先天性心脏病手术修复的儿童围手术期血浆中的MIF、白细胞介素(IL)-8和游离T4,并确定这些介质的反应是否能决定术后结果。术前、抵达儿科重症监护病房(PICU)即刻以及术后12、24和48小时采集血浆样本。患者在PICU接受持续监测,每天记录反映所提供治疗的侵入性、强度和复杂性的数据(治疗干预评分系统,TISS)。术前血浆MIF、IL-8和游离T4与年龄匹配的健康儿童无差异。然而,体外循环结束后2小时血浆MIF和IL-8显著升高,然后在24小时内恢复正常。术后MIF(48±24 ng/mL)和IL-8(79±57 pg/mL)的峰值水平与体外循环持续时间显著相关。术后血浆MIF升高的幅度与机械通气所需天数增加相关(r = 0.553;P = 0.012),血浆IL-8峰值与术后即刻所需吸入氧分数(FiO₂)显著相关(r = 0.510;P = 0.02)。术后第二天循环MIF水平较高与强心支持需求增加显著相关,而术后IL-8水平较高与TISS评分较高相关,表明术后医疗需求增加。这些数据表明术后即刻循环中高MIF水平对呼吸和心血管功能有潜在负面影响,并支持在这种临床环境中制定针对MIF功能的治疗策略。