Fischer Matthew A, Howard-Quijano Kimberly, Zong Nobel Chenggong, Youn Ji Youn, Liu Norika Mengchia, Scovotti Jennifer, Grogan Tristan, Mahajan Aman, Cai Hua
Department of Anesthesiology & Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Department of Anesthesiology & Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Antioxidants (Basel). 2024 Aug 9;13(8):971. doi: 10.3390/antiox13080971.
Postoperative atrial fibrillation (POAF) and acute kidney injury (AKI) are common yet significant complications after cardiac surgery, with incidences of up to 40% for each. Here, we assessed plasma nitrite and serum interleukin-6 (IL-6) levels before and after cardiac surgery to quantify the extent to which oxidative stress and inflammation contribute to POAF and AKI occurrence. We prospectively enrolled 206 cardiac surgical patients. Plasma nitrite and serum IL-6 levels were determined preoperatively and at 24 h, 48 h and 72 h postoperatively. The patients had continuous EKG monitoring for occurrence of POAF, while daily serum creatinine was measured for determination of stage 1 + AKI. Postoperatively, 78 (38%) patients experienced AF, and 47 (23%) patients experienced stage 1 + AKI. : Age, ACE-inhibitor use, valve surgery and percent change in baseline plasma nitrite at 24 h postoperatively were associated with POAF in multiple logistic regression analysis. The inclusion of this new biomarker significantly improved the POAF prediction model (AUC 0.77 for clinical risk factors alone, to AUC 0.81). : A history of diabetes mellitus was associated with AKI in multiple logistic regression analysis, and the addition of preoperative IL-6 levels improved the prediction model for AKI occurrence (AUC 0.69 to AUC 0.74). We previously observed selective upregulation of NADPH oxidase isoform 4 (NOX4) in patients with AF, a critical causal role of NOX4 for AF in zebrafish and a robust inhibitory effect of nitric oxide (NO) on NOX4. Our data innovatively demonstrate that a reduction in circulating nitrite levels, likely implicative of elevated NOX4-mediated oxidative stress, independently associates with POAF and improves POAF prediction, whereas the inclusion of circulating IL-6 levels improves the prediction model for AKI. Therefore, therapeutic strategies to mitigate these pathophysiological sequalae of surgical stress may reduce the incidence of severe postoperative complications of POAF and AKI.
术后心房颤动（POAF）和急性肾损伤（AKI）是心脏手术后常见且严重的并发症，二者发生率均高达40%。在此，我们评估了心脏手术前后血浆亚硝酸盐和血清白细胞介素-6（IL-6）水平，以量化氧化应激和炎症对POAF和AKI发生的影响程度。我们前瞻性纳入了206例心脏手术患者。术前及术后24小时、48小时和72小时测定血浆亚硝酸盐和血清IL-6水平。对患者进行连续心电图监测以观察POAF的发生情况，同时每日测定血清肌酐以确定1期+AKI。术后，78例（38%）患者发生房颤，47例（23%）患者发生1期+AKI。在多因素逻辑回归分析中，年龄、使用血管紧张素转换酶抑制剂、瓣膜手术以及术后24小时基线血浆亚硝酸盐的变化百分比与POAF相关。纳入这一新生物标志物显著改善了POAF预测模型（仅临床危险因素时AUC为0.77，加入新标志物后AUC为0.81）。在多因素逻辑回归分析中，糖尿病病史与AKI相关，加入术前IL-6水平可改善AKI发生的预测模型（AUC从0.69提高到0.74）。我们之前观察到房颤患者中NADPH氧化酶亚型4（NOX4）选择性上调，NOX4在斑马鱼房颤中起关键因果作用，一氧化氮（NO）对NOX4有强大抑制作用。我们的数据创新性地表明，循环亚硝酸盐水平降低可能意味着NOX4介导的氧化应激升高，这与POAF独立相关并改善了POAF预测，而加入循环IL-6水平则改善了AKI的预测模型。因此，减轻手术应激这些病理生理后果的治疗策略可能会降低POAF和AKI等严重术后并发症的发生率。
