Cavalca Viviana, Tremoli Elena, Porro Benedetta, Veglia Fabrizio, Myasoedova Veronika, Squellerio Isabella, Manzone Daniela, Zanobini Marco, Trezzi Matteo, Di Minno Matteo Nicola Dario, Werba José Pablo, Tedesco Calogero, Alamanni Francesco, Parolari Alessandro
Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milan, Italy.
Interact Cardiovasc Thorac Surg. 2013 Dec;17(6):923-30. doi: 10.1093/icvts/ivt386. Epub 2013 Sep 7.
We investigated whether oxidative stress and the arginine/nitric oxide pathway differ in control subjects and in adult patients who are candidates for the three most common cardiac surgical operations: coronary bypass surgery, aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral valve repair for degenerative mitral insufficiency.
In this prospective observational study, we studied 165 consecutive patients undergoing surgery from January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with cardiovascular risk factors similar to surgery patients were also studied (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors involved in nitric oxide synthesis (arginine, symmetric and asymmetric dimethylarginine) were measured before surgery. Analysis of variance general linear models and principal component analysis were used for statistical analysis.
Surgical patients had increased levels of oxidative stress and decreased levels of antioxidants. Increased levels of nitric oxide inhibitor asymmetric dimethylarginine were detected in surgical candidates, suggesting arginine/nitric oxide pathway impairment. Concerning the differences among surgical procedures, higher oxidative stress and a major imbalance of the ratio between substrate and inhibitors of nitric oxide synthesis were evidenced in patients who were candidates for mitral valve repair with respect to coronary bypass surgery patients and patients with calcific non-rheumatic aortic stenosis.
Patients undergoing cardiac surgery have increased oxidative stress and a trend towards an impaired arginine/nitric oxide pathway with respect to Controls. Patients affected by mitral valve regurgitation show more pronounced perturbations in these pathways. The clinical implications of these findings need to be investigated.
我们研究了氧化应激以及精氨酸/一氧化氮途径在对照组与成年患者中是否存在差异,这些成年患者是三种最常见心脏外科手术的候选对象,即冠状动脉搭桥手术、因钙化性非风湿性主动脉瓣狭窄进行主动脉瓣置换术或因退行性二尖瓣关闭不全进行二尖瓣修复术。
在这项前瞻性观察研究中,我们研究了2011年1月至6月期间连续接受手术的165例患者(冠状动脉搭桥手术,n = 63;因钙化性非风湿性主动脉瓣狭窄进行主动脉瓣置换术,n = 51;因退行性二尖瓣关闭不全进行二尖瓣修复术,n = 51)。还研究了33名具有与手术患者相似心血管危险因素的健康受试者(对照组)。在手术前测量氧化应激(还原型谷胱甘肽与氧化型谷胱甘肽的比率以及尿中异前列腺素)、抗氧化剂(α-和γ-生育酚)以及参与一氧化氮合成的因子(精氨酸、对称和不对称二甲基精氨酸)。采用方差分析一般线性模型和主成分分析进行统计分析。
手术患者的氧化应激水平升高,抗氧化剂水平降低。在手术候选者中检测到一氧化氮抑制剂不对称二甲基精氨酸水平升高,提示精氨酸/一氧化氮途径受损。关于手术方式之间的差异,与冠状动脉搭桥手术患者和钙化性非风湿性主动脉瓣狭窄患者相比,二尖瓣修复术候选患者的氧化应激水平更高,一氧化氮合成底物与抑制剂之间的比率失衡更严重。
与对照组相比,接受心脏手术的患者氧化应激增加,精氨酸/一氧化氮途径有受损趋势。受二尖瓣反流影响的患者在这些途径中表现出更明显的紊乱。这些发现的临床意义需要进一步研究。