Number of Circulating CD73‐Expressing Lymphocytes Correlates With Survival After Cardiac Arrest

Abstract

Background Patients resuscitated from cardiac arrest ( CA ) have highly variable neurological, circulatory, and systemic ischemia‐reperfusion injuries. After the initial hypoxic‐ischemic insult, a cascade of immune and inflammatory responses develops and is often fatal. The role of the immune response in pathophysiological characteristics and recovery is not well understood. We studied immune cell activity and its association with outcomes in a cohort of CA survivors. Methods and Results After informed consent, we collected blood samples at intervals over a week after resuscitation from CA . We examined the expression of CD 39 and CD 73 (alias 5′‐nucleotidase), production of tumor necrosis factor‐α, generation of reactive oxygen species, and secretion of vascular endothelial growth factor by circulating myeloid and lymphoid cells, in comparison to cells obtained from control subjects before coronary artery bypass grafting surgery. The number of circulating total and CD 73‐expressing lymphocytes correlated with survival after CA . Incubation of immune cells, obtained from post‐ CA subjects, with AMP , a substrate for CD 73, resulted in inhibition of tumor necrosis factor‐α production and generation of reactive oxygen species. This effect was blocked by adenosine 5′‐(α, β‐methylene) diphosphate, a specific inhibitor of CD 73 and ZM 241385, an A2 adenosine receptor antagonist. We also found that AMP ‐dependent activation of CD 73 induces production of vascular endothelial growth factor. Conclusions CD 73‐expressing lymphocytes mediate cellular protection from inflammation after CA through inhibition of proinflammatory activation of myeloid cells and promotion of vascular endothelial growth factor secretion. The contribution of CD 73 lymphocytes in the regulation of acute inflammation and tissue injury after CA warrants further study.

Single-cell transcriptomics reveal hyperacute cytokine and immune checkpoint axis in patients with poor neurological outcomes after cardiac arrest

“…Our study corroborated some findings from the limited immunophenotyping of prior studies in clinical CA (Asmussen et al, 2021; Kim et al, 2018; Miyatake et al, 2019; Ryzhov et al, 2019; Villois et al, 2017; Wei ser et al, 2017). For example, a prior study (Asmussen et al, 2021) associated reduced expression of HLA-DR on monocytes with poor outcomes after CA.…”

Fingerprint of Circulating Immunocytes as Biomarkers for the Prognosis of Brain Inflammation and Neuronal Injury after Cardiac Arrest

“…Only 5–9% of peripheral blood cells in mice are granulocytes, of which the large majority are neutrophils, accounting for 30–40% of the mouse white blood cells . The plasticity of these myeloid-derived populations correlates with survival and controls the body’s immune defense. , In this study, the myeloid-derived CD11b + CD11c + and CD11b – CD11c + DCs and CD11b + Ly6C + Ly6G + PMN-MDSCs were upregulated in the blood after CAR. PMN-MDSCs are pathologically activated neutrophils and monocytes, which play a role in the immune response to injuries.…”

High platelet-lymphocyte ratio is a risk factor for 30-day mortality in in-hospital cardiac arrest patients: a case-control study

“…These ndings are inconsistent with the results of our study. First, these discrepancies can be explained by the heterogeneity of the study population; 80% of the patients had OHCA in Ryzhov's study [30], while the target population of our study was IHCA patients. In addition, the use of drugs in the early stage after cardiac arrest may affect the dynamic changes of related indicators; for example, corticosteroids can lead to lymphopenia after cardiac arrest [23].…”

“…Many recent studies on sepsis and other severe diseases [27][28][29] have shown that the NLR, PLR and SII can continue to decrease in the early stage of disease, which is consistent with the conclusion of our study. However, Ryzhov et al [30] showed that the AMC increases brie y within 6 h after ROSC, the ALC shows a persistent decrease 6-72 h after ROSC, and the ANC and WBC count increase signi cantly within 48 h and 72-168 h after ROSC. These ndings are inconsistent with the results of our study.…”