Department of Surgery, Maastricht University Medical Center Maastricht, Netherlands ; NUTRIM School for Nutrition, Toxicology & Metabolism, Maastricht University Medical Center Maastricht, Netherlands.
Central Diagnostic Laboratory, Maastricht University Medical Center Maastricht, Netherlands.
Front Physiol. 2014 Sep 8;5:340. doi: 10.3389/fphys.2014.00340. eCollection 2014.
Acute kidney injury (AKI) and intestinal injury negatively impact patient outcome after cardiac surgery. Enhanced nitric oxide (NO) consumption due to intraoperative intravascular hemolysis, may play an important role in this setting. This study investigated the impact of hemolysis on plasma NO consumption, AKI, and intestinal tissue damage, after cardiac surgery.
Hemolysis (by plasma extracellular (free) hemoglobin; fHb), plasma NO-consumption, plasma fHb-binding capacity by haptoglobin (Hp), renal tubular injury (using urinary N-Acetyl-β-D-glucosaminidase; NAG), intestinal mucosal injury (through plasma intestinal fatty acid binding protein; IFABP), and AKI were studied in patients undergoing off-pump cardiac surgery (OPCAB, N = 7), on-pump coronary artery bypass grafting (CABG, N = 30), or combined CABG and valve surgery (CABG+Valve, N = 30).
FHb plasma levels and NO-consumption significantly increased, while plasma Hp concentrations significantly decreased in CABG and CABG+Valve patients (p < 0.0001) during surgery. The extent of hemolysis and NO-consumption correlated significantly (r (2) = 0.75, p < 0.0001). Also, NAG and IFABP increased in both groups (p < 0.0001, and p < 0.001, respectively), and both were significantly associated with hemolysis (R s = 0.70, p < 0.0001, and R s = 0.26, p = 0.04, respectively) and NO-consumption (Rs = 0.55, p = 0.002, and R s = 0.41, p = 0.03, respectively), also after multivariable logistic regression analysis. OPCAB patients did not show increased fHb, NO-consumption, NAG, or IFABP levels. Patients suffering from AKI (N = 9, 13.4%) displayed significantly higher fHb and NAG levels already during surgery compared to non-AKI patients.
Hemolysis appears to be an important contributor to postoperative kidney injury and intestinal mucosal damage, potentially by limiting NO-bioavailability. This observation offers a novel diagnostic and therapeutic target to improve patient outcome after cardiothoracic surgery.
急性肾损伤（AKI）和肠道损伤会对心脏手术后患者的预后产生负面影响。术中血管内溶血导致的一氧化氮（NO）消耗增加可能在这种情况下发挥重要作用。本研究调查了心脏手术后溶血对血浆 NO 消耗、AKI 和肠道组织损伤的影响。
研究了接受非体外循环心脏手术（OPCAB，N = 7）、体外循环冠状动脉旁路移植术（CABG，N = 30）或 CABG 联合瓣膜手术（CABG+Valve，N = 30）的患者的溶血（通过血浆细胞外（游离）血红蛋白；fHb）、血浆 NO 消耗、血浆 Hp 对 fHb 的结合能力（触珠蛋白；Hp）、肾小管损伤（通过尿 N-乙酰-β-D-氨基葡萄糖苷酶；NAG）、肠道黏膜损伤（通过血浆肠脂肪酸结合蛋白；IFABP）和 AKI。
在 CABG 和 CABG+Valve 患者的手术过程中，fHb 血浆水平和 NO 消耗显著增加，而 Hp 浓度显著降低（p < 0.0001）。溶血和 NO 消耗之间存在显著相关性（r（2）= 0.75，p < 0.0001）。此外，两组患者的 NAG 和 IFABP 均增加（p < 0.0001 和 p < 0.001），且均与溶血（Rs = 0.70，p < 0.0001 和 Rs = 0.26，p = 0.04）和 NO 消耗（Rs = 0.55，p = 0.002 和 Rs = 0.41，p = 0.03）显著相关，即使在多变量逻辑回归分析后也是如此。OPCAB 患者未显示出 fHb、NO 消耗、NAG 或 IFABP 水平增加。发生 AKI 的患者（n = 9，13.4%）在手术期间与非 AKI 患者相比，fHb 和 NAG 水平明显升高。
溶血似乎是术后肾损伤和肠道黏膜损伤的一个重要原因，可能是通过限制 NO 的生物利用度。这一观察结果为改善心胸外科手术后患者的预后提供了一个新的诊断和治疗靶点。
