Brain and heart injury cause most out-of-hospital cardiac arrest deaths but limited pharmacotherapy exists to protect these tissues. Nitrite is a nitric oxide precursor that is protective in pre-clinical models of ischemic injury and safe in Phase I testing. Protection may occur by cGMP generation via the sGC pathway or through S-nitrosothiol and nitrated conjugated linoleic acid (NO₂-CLA) formation. We hypothesized that nitrite provided during CPR signals through multiple pathways and that activation of signals is associated with OHCA outcome. To this end, we performed a secondary analysis of a phase 1 study of intravenous nitrite administration during resuscitation in adult out-of-hospital cardiac arrest. Associations between whole blood nitrite and derived plasma signals (cGMP and NO₂-CLA) with patient characteristics and outcomes were defined using Chi-square or t-tests and multiple logistic regression. Whole blood nitrite levels correlated inversely with plasma NO₂-CLA (p = 0.039) but not with cGMP. Patients with shockable rhythms had higher cGMP (p = 0.027), NO₂-CLA (p < 0.0001) and trended towards lower nitrite (p = 0.077). Importantly, plasma cGMP and NO₂-CLA levels were higher in survivors (p = 0.033 and 0.019) and in those with good neurological outcome (p = 0.046 and 0.021). Nitrite was lower in patients with good neurologic outcome (p = 0.029). cGMP (OR 4.02; 95% CI 1.04–15.54; p = 0.044) and NO₂-CLA (OR 3.74; 95% CI 1.11–12.65; p = 0.034) were associated with survival. Nitrite (OR 0.20; 95% CI 0.05–0.08; p = 0.026) and NO₂-CLA (OR 3.96; 95% CI 1.01–15.60; p = 0.049) were associated with favorable neurologic outcome. In summary, nitrite administration was associated with increased plasma cGMP and NO₂-CLA formation in selected OHCA patients. Furthermore, patients with the highest levels of cGMP and NO₂-CLA were more likely to survive and experience better neurological outcomes.

脑和心脏损伤导致大多数院外心脏骤停死亡，但保护这些组织的药物疗法有限。亚硝酸盐是一种一氧化氮前体，在缺血性损伤的临床前模型中具有保护作用，在 I 期测试中是安全的。保护可以通过 sGC 途径产生 cGMP 或通过 S-亚硝基硫醇和硝化共轭亚油酸 (NO ₂ -CLA) 形成来实现。我们假设在 CPR 信号期间通过多种途径提供亚硝酸盐，并且信号的激活与 OHCA 的结果相关。为此，我们对成人院外心脏骤停复苏期间静脉注射亚硝酸盐的 1 期研究进行了二次分析。全血亚硝酸盐与衍生血浆信号（cGMP 和 NO ₂-CLA) 与患者特征和结果使用卡方或 t 检验和多元逻辑回归进行定义。全血亚硝酸盐水平与血浆 NO ₂ -CLA 呈负相关（p = 0.039），但与 cGMP 无关。具有可电击节律的患者具有较高的 cGMP (p = 0.027)、NO ₂ -CLA (p < 0.0001) 并趋向于降低亚硝酸盐 (p = 0.077)。重要的是，血浆 cGMP 和 NO ₂ -CLA 水平在幸存者（p = 0.033 和 0.019）和神经系统预后良好的人（p = 0.046 和 0.021）中更高。神经系统预后良好的患者亚硝酸盐含量较低（p = 0.029）。cGMP（OR 4.02；95% CI 1.04–15.54；p = 0.044）和 NO ₂-CLA（OR 3.74；95% CI 1.11–12.65；p = 0.034）与生存率相关。亚硝酸盐（OR 0.20；95% CI 0.05–0.08；p = 0.026）和 NO ₂ -CLA（OR 3.96；95% CI 1.01–15.60；p = 0.049）与良好的神经系统结局相关。总之，亚硝酸盐给药与选定的 OHCA 患者的血浆 cGMP 和 NO _{2 -CLA 形成增加有关。}此外，具有最高水平 cGMP 和 NO ₂ -CLA 的患者更有可能存活并经历更好的神经系统结果。