Shoaib Muhammad, Nishikimi Mitsuaki, Choudhary Rishabh C, Yagi Tsukasa, Hayashida Kei, Yin Tai, Espin Blanca B, Becker Lance B, Kim Junhwan
Laboratory for Critical Care Physiology, The Feinstein Institutes for Medical Research, Manhasset, NY, United States.
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States.
Front Pharmacol. 2025 Aug 21;16:1587776. doi: 10.3389/fphar.2025.1587776. eCollection 2025.
Cardiac arrest (CA) results in a loss of blood circulation, leading to whole-body ischemia-reperfusion injuries. A deficiency in plasma lysophosphatidylcholine (LPC) levels has been observed in both human patients and rat models and is implicated in organ dysfunction following CA. Building on previous findings from a mild injury model, this study explored the therapeutic potential of LPC supplementation in a severe 12-min rat CA model. The study also compared the effects of combining multiple LPC species with individual species to better determine the most effective strategy and enhance the translational potential of LPC therapy for CA treatment. We found that LPC supplementation, particularly with LPC(18:1) alone and in combination with other LPC species, significantly improved 72-h survival rates. However, combination therapy offered superior protection compared to single LPC species, as assessed by modified neurological deficit score (mNDS). Additionally, combination therapy reduced troponin I levels, indicating cardioprotection, and facilitated the return of the N10 peak in somatosensory evoked potentials, suggesting preserved nervous system integrity. While individual LPC species offered some benefits, combination therapy yielded superior results. The significant improvements in outcomes observed in this severe model highlight the robustness of LPC therapy and its potential to treat CA patients with varying injury severities. Specifically, the use of LPC in combination emerges as a promising strategy for mitigating organ damage and enhancing recovery outcomes post-CA.
心脏骤停（CA）会导致血液循环丧失，进而引发全身缺血再灌注损伤。在人类患者和大鼠模型中均观察到血浆溶血磷脂酰胆碱（LPC）水平不足，且这与CA后的器官功能障碍有关。基于先前轻度损伤模型的研究结果，本研究探索了在严重的12分钟大鼠CA模型中补充LPC的治疗潜力。该研究还比较了多种LPC种类与单一LPC种类联合使用的效果，以更好地确定最有效的策略，并提高LPC治疗CA的转化潜力。我们发现，补充LPC，特别是单独使用LPC（18:1）以及与其他LPC种类联合使用时，能显著提高72小时生存率。然而，通过改良神经功能缺损评分（mNDS）评估，联合治疗比单一LPC种类提供了更好的保护。此外，联合治疗降低了肌钙蛋白I水平，表明具有心脏保护作用，并促进了体感诱发电位中N10波峰的恢复，提示神经系统完整性得以保留。虽然单一LPC种类有一定益处，但联合治疗效果更佳。在这个严重模型中观察到的结果显著改善，凸显了LPC治疗的有效性及其治疗不同损伤严重程度CA患者的潜力。具体而言，联合使用LPC成为减轻器官损伤和改善CA后恢复结果的一种有前景的策略。
