Ondracek A S, Hofbauer T M, Wurm R, Arfsten H, Seidl V, Früh A, Seidel S, Hubner P, Mangold A, Goliasch G, Heinz G, Lang I M, Sterz F, Adlbrecht C, Distelmaier K
Department of Internal Medicine II, Medical University of Vienna, Austria.
Department of Neurology, Medical University of Vienna, Austria.
Resuscitation. 2020 Jun;151:26-32. doi: 10.1016/j.resuscitation.2020.03.006. Epub 2020 Apr 3.
Despite an increased rate of return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) patients, almost half of patients do not survive up to hospital discharge. Understanding pathophysiological mechanisms of post-cardiac arrest syndrome is essential for developing novel therapeutic strategies. During systemic inflammatory responses and concomitant cell death, double-stranded (ds) DNA is released into circulation, exerting pro-inflammatory effects. Deoxyribonuclease (DNase) degrades dsDNA. The role of DNase activity in OHCA survivors and impact on clinical outcome has not been analyzed yet.
In a prospective, single-center study, dsDNA and DNase activity were determined at hospital admission (acute phase) and 24 h (subacute phase) after ROSC. The ratio between dsDNA levels and DNase activity was calculated to determine the extent of dsDNA release in relation to the patients' capacity of degradation. Thirty-day mortality was defined as study end point.
We enrolled 64 OHCA survivors, of whom 26.6% (n = 17) died within 30 days. A peak of circulating dsDNA was observed at admission which decreased within 24 h. DNase activity did not differ between acute and subacute phase, while dsDNA load per DNase activity significantly decreased. The ratio between dsDNA levels and DNase activity in the subacute phase was the strongest predictor of 30-day mortality with an adjusted HR per 1 SD of 3.59 (95% CI, 1.80-7.18, p < 0.001).
Disproportionally increased dsDNA levels uncompensated by DNase activity are a strong predictor of mortality in OHCA survivors. This pilot study points to a potentially protective effect of DNase activity in patients undergoing cardiac arrest.
尽管院外心脏骤停（OHCA）患者自主循环恢复（ROSC）率有所提高，但几乎一半的患者未能存活至出院。了解心脏骤停后综合征的病理生理机制对于开发新的治疗策略至关重要。在全身炎症反应和伴随的细胞死亡过程中，双链（ds）DNA释放到循环中，发挥促炎作用。脱氧核糖核酸酶（DNase）可降解dsDNA。尚未分析DNase活性在OHCA幸存者中的作用及其对临床结局的影响。
在一项前瞻性单中心研究中，于患者入院时（急性期）及ROSC后24小时（亚急性期）测定dsDNA和DNase活性。计算dsDNA水平与DNase活性之间的比值，以确定dsDNA释放程度与患者降解能力的关系。将30天死亡率定义为研究终点。
我们纳入了64名OHCA幸存者，其中26.6%（n = 17）在30天内死亡。入院时观察到循环dsDNA达到峰值，24小时内下降。急性期和亚急性期的DNase活性无差异，而每单位DNase活性的dsDNA负荷显著降低。亚急性期dsDNA水平与DNase活性的比值是30天死亡率的最强预测指标，每增加1个标准差，校正后的风险比为3.59（95%可信区间，1.80 - 7.18，p < 0.001）。
未被DNase活性代偿的dsDNA水平不成比例增加是OHCA幸存者死亡率的有力预测指标。这项初步研究表明DNase活性对心脏骤停患者可能具有保护作用。
