AIMS Heart disease of different aetiology remains the leading cause of cardiac arrest (CA). Despite efforts to improve the quality of cardiopulmonary resuscitation (CPR), subsequent myocardial and systemic damage after CA still present a major long-term burden. Low-dose carbon monoxide (CO) is known to exert protective effects in cardiovascular pathophysiology but clinical applications are challenged by unfavourable delivery modes. We tested the hypothesis that extracorporeal resuscitation (E-CPR) in combination with controlled fast onset CO delivery results in improved cardiac physiology and haemodynamics. Damage-associated molecular pattern (DAMP) signalling may be part of the molecular mechanism. METHODS AND RESULTS In an established porcine model, E-CPR was performed. While E-CPR leads to similar results as compared to a conventional CPR strategy, CO delivery in combination with E-CPR demonstrated significant cardioprotection. Cardiac performance analysis using echocardiography and thermodilution techniques showed a CO-dependent improved cardiac function compared to severe myocardial dysfunction in CPR and E-CPR (left ventricular ejection fraction: Sham 49 ± 5; CPR 26 ± 2; E-CPR 25 ± 2; CO-E-CPR 31 ± 4; P < 0.05). While sublingual microcirculation was significantly compromised in CPR and E-CPR, CO delivery demonstrated a significant improvement in microvascular function (microvascular flow index: Sham 2.9 ± 0.1; CPR 2.2 ± 0.1; E-CPR 1.8 ± 0.1; CO-E-CPR 2.7 ± 0.1; P < 0.01). Histological and serological myocardial damage markers were significantly reduced (hsTroponin-T Sham 0.01 ± 0.001; CPR 1.9 ± 0.2; E-CPR 3.5 ± 1.2; CO-E-CPR 0.5 ± 0.2 ng/mL; P < 0.05). DAMP signalling was decreased ipse facto leading to influence of cardioprotective heat shock and cyclooxygenase response. CONCLUSIONS CO treatment restores myocardial function and improves systemic macro- and microhaemodynamics in E-CPR through a reduction in DAMPs.

中文翻译：

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一氧化碳可改善猪体外复苏过程中的血流动力学。

目的不同病因的心脏病仍然是心脏骤停（CA）的主要原因。尽管努力改善心肺复苏（CPR）的质量，但CA后继发的心肌和全身损害仍是长期的主要负担。低剂量一氧化碳（CO）在心血管病理生理中发挥保护作用，但临床应用受到不利的给药方式的挑战。我们测试了以下假设，即体外复苏（E-CPR）与受控的快速起效一氧化碳释放相结合，可改善心脏生理和血流动力学。损伤相关分子模式（DAMP）信号可能是分子机制的一部分。方法和结果在建立的猪模型中，进行了E-CPR。尽管与传统的CPR策略相比，E-CPR可获得相似的结果，但CO递送结合E-CPR表现出显着的心脏保护作用。使用超声心动图和热稀释技术进行的心脏功能分析显示，与CPR和E-CPR中严重的心肌功能不全相比，CO依赖的心功能得到改善（左心室射血分数：Sham 49±5； CPR 26±2； E-CPR 25±2；和CO-E-CPR 31±4; P <0.05）。虽然舌下微循环在CPR和E-CPR中显着受损，但CO递送显示出微血管功能的显着改善（微血管流动指数：Sham 2.9±0.1; CPR 2.2±0.1; E-CPR 1.8±0.1; CO-E-CPR 2.7 ±0.1; P <0.01）。组织学和血清学方面的心肌损伤标志物显着降低（hsTroponin-T Sham 0.01±0.001; CPR 1.9±0.2; E-CPR 3.5±1.2; CO-E-CPR 0.5±0.2 ng / mL; P <0.05）。DAMP信号转而降低，从而导致心脏保护性热休克和环氧合酶反应的影响。结论CO治疗可通过减少DAMPs来恢复心肌功能，并改善E-CPR的全身宏观和微观血液动力学。