Diamond Joshua M, Porteous Mary K, Roberts L Jackson, Wickersham Nancy, Rushefski Melanie, Kawut Steven M, Shah Rupal J, Cantu Edward, Lederer David J, Chatterjee Shampa, Lama Vibha N, Bhorade Sangeeta, Crespo Maria, McDyer John, Wille Keith, Orens Jonathan, Weinacker Ann, Arcasoy Selim, Shah Pali D, Wilkes David S, Hage Chadi, Palmer Scott M, Snyder Laurie, Calfee Carolyn S, Ware Lorraine B, Christie Jason D
Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee.
J Heart Lung Transplant. 2016 Apr;35(4):500-507. doi: 10.1016/j.healun.2015.12.012. Epub 2016 Jan 7.
Donor smoking history and higher fraction of inspired oxygen (FIO2) at reperfusion are associated with primary graft dysfunction (PGD) after lung transplantation. We hypothesized that oxidative injury biomarkers would be elevated in PGD, with higher levels associated with donor exposure to cigarette smoke and recipient hyperoxia at reperfusion.
We performed a nested case-control study of 72 lung transplant recipients from the Lung Transplant Outcomes Group cohort. Using mass spectroscopy, F2-isoprostanes and isofurans were measured in plasma collected after transplantation. Cases were defined in 2 ways: grade 3 PGD present at day 2 or day 3 after reperfusion (severe PGD) or any grade 3 PGD (any PGD).
There were 31 severe PGD cases with 41 controls and 35 any PGD cases with 37 controls. Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (28.6 pg/ml vs 19.8 pg/ml, p = 0.03). Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (29.6 pg/ml vs 19.0 pg/ml, p = 0.03) among patients reperfused with FIO2 >40%. Among recipients of lungs from donors with smoke exposure, plasma F2-isoprostane (38.2 pg/ml vs 22.5 pg/ml, p = 0.046) and isofuran (66.9 pg/ml vs 34.6 pg/ml, p = 0.046) levels were higher in severe PGD compared with control subjects.
Plasma levels of lipid peroxidation products are higher in patients with severe PGD, in recipients of lungs from donors with smoke exposure, and in recipients exposed to higher Fio2 at reperfusion. Oxidative injury is an important mechanism of PGD and may be magnified by donor exposure to cigarette smoke and hyperoxia at reperfusion.
供体吸烟史以及再灌注时较高的吸入氧分数(FIO2)与肺移植后的原发性移植物功能障碍(PGD)相关。我们推测氧化损伤生物标志物在PGD中会升高,且较高水平与供体接触香烟烟雾以及受体再灌注时的高氧状态有关。
我们对来自肺移植结果研究组队列的72例肺移植受者进行了一项巢式病例对照研究。使用质谱法测量移植后采集的血浆中的F2-异前列腺素和异呋喃。病例以两种方式定义:再灌注后第2天或第3天出现3级PGD(严重PGD)或任何3级PGD(任何PGD)。
有31例严重PGD病例和41例对照,以及35例任何PGD病例和37例对照。与对照组相比,严重PGD病例的血浆F2-异前列腺素水平更高(28.6 pg/ml对19.8 pg/ml,p = 0.03)。在FIO2>40%进行再灌注的患者中,严重PGD病例的血浆F2-异前列腺素水平也高于对照组(29.6 pg/ml对19.0 pg/ml,p = 0.03)。在接受有吸烟暴露供体肺的受者中,与对照受试者相比,严重PGD患者的血浆F2-异前列腺素(38.2 pg/ml对22.5 pg/ml,p = 0.046)和异呋喃(66.9 pg/ml对34.6 pg/ml,p = 0.046)水平更高。
严重PGD患者、接受有吸烟暴露供体肺的受者以及再灌注时暴露于较高Fio2的受者的血浆脂质过氧化产物水平更高。氧化损伤是PGD的重要机制,并且可能因供体接触香烟烟雾和再灌注时的高氧状态而加剧。