a Biochemistry and Molecular Biology, Interdisciplinary Research Center , Justus Liebig University , Giessen , Germany.
b Clinic for Heart, Pediatric Heart and Vascular Surgery, Faculty of Medicine , UKGM , Giessen , Germany.
Redox Rep. 2018 Dec;23(1):83-93. doi: 10.1080/13510002.2017.1418620. Epub 2017 Dec 19.
Redox regulation plays a crucial role in balancing the cardiovascular system. In this prospective study we aimed to identify currently unknown correlations valuable to cardiovascular research and patient management.
Blood samples from 500 patients were collected directly before cardiosurgical interventions (Ethics Committee reference number 85/11). Four central redox parameters were determined together with about 30 clinical, anthropometric, and metabolic parameters.
Creatinine levels and pulmonary hypertension were significant predictors of the total antioxidant status (TAOS) in the patients; total glutathione levels were linked to C-peptide, and creatinine, gender, and ventricular arrhythmia influenced nitrate/nitrite levels. Notably, significant interactions were found between medication and redox parameters. Calcium channel blockers (CCBs) were positive predictors of total glutathione levels, whereas angiotensin-converting enzyme inhibitors and CCBs were negative predictors of NOx levels. Age showed the highest correlation with the duration of the intensive care stay, followed by NOx levels, creatinine, TAOS, and C-reactive protein.
In this prospective study we determined multiple correlations between redox markers and parameters linked to cardiovascular diseases. The data point towards so far unknown interdependencies, particularly between antihypertensive drugs and redox metabolism. A thorough follow-up to these data has the potential to improve patient management.
A: absorption; ΔA: absorption difference; ABTS: 2,2'-azino-di(3-ethylbenzothiazoline sulfonate); ACE: angiotensin-converting enzyme; AO: antioxidant; ARB: angiotensin receptor blocker; BMI: body mass index; CAD: coronary artery disease; CCB: calcium channel blocker; CDC: coronary heart diseases; COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; CVD: cardiovascular diseases; Cu-OOH: cumene hydroperoxide; D: dilution factor; DAN: 2,3-diaminonaphtalene; DMSO: dimethylsulfoxide; DNA: deoxyribonucleic acid; DTNB: 5,5-dithiobis(2-nitrobenzoate); ε: extinction coefficient; EDRF: endothelium-derived relaxing factor; fc: final concentration; GPx: glutathione peroxidases; (h)GR: (human) glutathione reductase; GSH: (reduced) glutathione; GSSG: glutathione disulfide; GST: glutathione-S-transferase; Hb: hemoglobin; HDL: high-density lipoprotein; Hk: hematocrit; HO: hydrogen peroxide; ICS: intensive care stay; LDH: lactate dehydrogenase; LDL: low-density lipoprotein; MI: myocardial infarction; NED: N-(1-naphthyl)-ethylendiamine-dihydrochloride; NOS: nitric oxide synthase; NOx: nitrate/nitrite; NR: nitrate reductase; PBS: phosphate buffered saline; PCA: principle component analysis; PH: pulmonary hypertension; ROS: reactive oxygen species; RNS: reactive nitrogen species; RT: room temperature (25°C); SA: sulfanilamide; SOD: superoxide dismutase; SSA: sulfosalicylic acid; TAC: total antioxidant capacity; TAOS: total antioxidant status; TEAC: trolox equivalent antioxidative capacity; TG: triglycerides; tGSH: total glutathione; TNB-: 2-nitro-5-thiobenzoate; U: unit; UV: ultraviolet; VA: volume activity; Wc: working concentration; WHR: waist-hip ratio.
氧化还原调节在平衡心血管系统中起着至关重要的作用。在这项前瞻性研究中,我们旨在确定目前对心血管研究和患者管理有价值的未知相关性。
在心脏外科手术干预前直接采集了 500 名患者的血液样本(伦理委员会参考号 85/11)。同时测定了 4 个中心氧化还原参数以及约 30 个临床、人体测量和代谢参数。
肌酐水平和肺动脉高压是患者总抗氧化状态(TAOS)的显著预测因素;总谷胱甘肽水平与 C 肽有关,肌酐、性别和室性心律失常影响硝酸盐/亚硝酸盐水平。值得注意的是,在药物和氧化还原参数之间发现了显著的相互作用。钙通道阻滞剂(CCB)是总谷胱甘肽水平的正预测因子,而血管紧张素转换酶抑制剂和 CCB 是 NOx 水平的负预测因子。年龄与重症监护停留时间的相关性最高,其次是 NOx 水平、肌酐、TAOS 和 C 反应蛋白。
在这项前瞻性研究中,我们确定了氧化还原标志物与心血管疾病相关参数之间的多种相关性。这些数据指向迄今为止未知的相互依存关系,特别是在抗高血压药物和氧化还原代谢之间。对这些数据进行深入的随访有可能改善患者的管理。
A:吸收;ΔA:吸收差;ABTS:2,2'-偶氮双(3-乙基苯并噻唑啉-6-磺酸);ACE:血管紧张素转换酶;AO:抗氧化剂;ARB:血管紧张素受体阻滞剂;BMI:体重指数;CAD:冠状动脉疾病;CCB:钙通道阻滞剂;CDC:冠心病;COPD:慢性阻塞性肺疾病;CRP:C 反应蛋白;CVD:心血管疾病;Cu-OOH:枯烯氢过氧化物;D:稀释因子;DAN:2,3-二氨基萘;DMSO:二甲基亚砜;DNA:脱氧核糖核酸;DTNB:5,5-二硫代双(2-硝基苯甲酸);ε:消光系数;EDRF:内皮衍生的松弛因子;fc:最终浓度;GPx:谷胱甘肽过氧化物酶;(h)GR:(人)谷胱甘肽还原酶;GSH:(还原)谷胱甘肽;GSSG:谷胱甘肽二硫化物;GST:谷胱甘肽-S-转移酶;Hb:血红蛋白;HDL:高密度脂蛋白;Hk:红细胞压积;HO:过氧化氢;ICS:重症监护停留时间;LDH:乳酸脱氢酶;LDL:低密度脂蛋白;MI:心肌梗死;NED:N-(1-萘基)-乙二胺二盐酸盐;NOS:一氧化氮合酶;NOx:硝酸盐/亚硝酸盐;NR:硝酸还原酶;PBS:磷酸盐缓冲盐水;PCA:主成分分析;PH:肺动脉高压;ROS:活性氧;RNS:活性氮;RT:室温(25°C);SA:磺胺;SOD:超氧化物歧化酶;SSA:磺基水杨酸;TAC:总抗氧化能力;TAOS:总抗氧化状态;TEAC:trolox 等效抗氧化能力;TG:甘油三酯;tGSH:总谷胱甘肽;TNB-:2-硝基-5-噻吩甲酰基;U:单位;UV:紫外线;VA:体积活性;Wc:工作浓度;WHR:腰臀比。