scholarly journals Monocyte subset distribution and surface expression of HLA-DR and CD14 in patients after cardiopulmonary resuscitation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander Asmussen ◽  
Hans-Jörg Busch ◽  
Thomas Helbing ◽  
Xavier Bemtgen ◽  
Christian Smolka ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Disease Severity ◽  
Ischemia Reperfusion Injury ◽  
Early Stage ◽  
Ischemia Reperfusion ◽  
Surface Expression ◽  
Significant Decline ◽  
Monocyte Subset ◽  
Hla Dr ◽  
Monocyte Subpopulations

AbstractSystemic inflammation is a major feature of the post-cardiac arrest syndrome. The three monocyte subpopulations are thought to play an important role in this inflammatory state because they are endowed with numerous pattern recognition receptors, such as CD14, that have been associated with ischemia–reperfusion injury. By contrast, an exaggerated antiinflammatory response has also been described following cardiac arrest, which may be mediated by downregulation of antigen presentation receptor HLA-DR. We report the composition of monocyte subpopulations and the expression of CD14 and HLA-DR following cardiac arrest. Blood specimens were collected from 32 patients at three timepoints in the first 48 h after cardiac arrest. Monocyte subset composition was determined by flow cytometry based on the expression of CD14, CD16, and HLA-DR. Monocyte subset composition and the expression of CD14 and HLA-DR were correlated with patient outcomes. The results were compared to 19 patients with coronary artery disease. Cardiac arrest patients showed a significant decline in the percentage of nonclassical monocytes. Monocyte CD14 expression was upregulated after 24 h and correlated with the time to return of spontaneous circulation. Downregulation of HLA-DR expression was observed mainly among classical monocytes and significantly correlated with the dose of norepinephrine used to treat shock. Downregulation of HLA-DR among nonclassical and intermediate monocytes was significantly associated with disease severity. Our data demonstrate the disturbance of monocyte subset composition with a significant decline in nonclassical monocytes at an early stage following cardiac arrest. Our findings suggest the simultaneous presence of hyperinflammation, as evidenced by upregulation of CD14, and monocyte deactivation, characterized by downregulation of HLA-DR. The extent of monocyte deactivation was significantly correlated with disease severity.

Abstract 138: Remote Ischemic Postconditioning Alleviates Postresuscitation Inflammatory Response and Pulmonary Edema in a Porcine Model of Cardiac Arrest

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jiefeng Xu ◽  
Sen Ye ◽  
Zilong Li ◽  
Moli Wang ◽  
Zhengquan Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Inflammatory Response ◽  
Pulmonary Edema ◽  
Porcine Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Limb Ischemia ◽  
Multiple Organ ◽  
Control Group ◽  
Lung Water

Introduction: Systemic ischemia-reperfusion injury produced by CA and resuscitation can result in severe post-cardiac arrest syndrome; which includes systemic inflammatory response and multiple organ dysfunction syndrome such as acute pulmonary edema. We previously demonstrated that remote ischemic post-conditioning (RIpostC) improved post-resuscitation myocardial and cerebral function in a rat model of CA. In this study, we investigated the effects of RIpostC on inflammatory response and pulmonary edema after CPR in a porcine model. Hypothesis: RIpostC would alleviate post-resuscitation inflammatory response and pulmonary edema in a porcine model of CA. Methods: Fourteen male domestic pigs weighing 37 ± 2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 10 mins. The animals were then randomized to receive RIpostC or control. Coincident with the start of CPR, RIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. Defibrillation was attempted after 5 mins of CPR. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs. Results: Six of the seven animals in each group were successfully resuscitated. After resuscitation, significantly lower levels of tumor necrosis factor-α and interleukin-6 were measured in the animals that received RIpostC when compared with the control group. Post-resuscitation extra-vascular lung water index was lower in the RIpostC group than in the control group; in which the differences were significant at 2,3 and 4 hrs (Table). Conclusion: In a porcine model of CA, RIpostC significantly alleviates post-resuscitation inflammatory response and pulmonary edema.

Abstract 595: Functional, Histologic, and Radiographic Characteristics of Global Ischemia-reperfusion Brain Injury in a Mouse Model Of Cardiac Arrest

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Akshay Pendyal ◽  
Cameron Dezfulian ◽  
Luhua Zhang ◽  
Jeeva Munasinghe ◽  
Mark T Gladwin
Keyword(s):  
Cardiac Arrest ◽  
Rectal Temperature ◽  
Diffusion Mri ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Global Ischemia ◽  
Neurological Injury ◽  
Strong Trend ◽  
Enhanced Mri ◽  
Neurological Score

Cardiac arrest (CA) and subsequent CPR constitute a clinically relevant form of global ischemia-reperfusion injury (IR). Global IR often results in widespread ischemic brain damage and severe neurologic sequelae. In the present study, we sought to describe the functional, histologic, and radiographic brain changes that occur following CA/CPR. 8–10 week old C57BL/6 mice were subjected to 12 minutes of normothermic cardioplegic CA and resuscitated with chest compressions, mechanical ventilation, and epinephrine. Sham mice underwent surgery, but not CA. At 3 and 24 hours, 10-point functional neurological score and rectal temperature were assessed prior to trans-cardiac perfusion with PBS and 10% buffered formalin. Sectioned brains were stained using hematoxylin and eosin (H/E) and the terminal deoxyuridine triphosphate nick end-labeling (TUNEL) technique. An additional cohort of mice underwent quantitative diffusion MRI at 24 and 72 hours, gadolinium (Gd)-enhanced MRI at 24 hours, and quantitative T2 imaging at 72 hours. Compared to shams, mice undergoing CA/CPR displayed significantly lower functional neurological score at 3 hours (3±2 vs. 10±0; P<.001) and 24 hours (8±1 vs. 10±0, P<.05), and significantly higher rectal temperature at 3 hours (35.8±1.5 vs. 34.1±0.8, P<.001) and lower rectal temperature at 24 hours (33.8±2.5 vs. 37.1±0.8, P=.08). TUNEL and H/E staining revealed injury in the cortex, thalamus, hippocampus, and cerebellum, but neither a consistent pattern nor clear temporal progression was observed. Gd-enhanced MRI revealed increased signal intensity, particularly in the cortex, after CA (3.7×105±0.96×105 vs. 0.66×105±0.017×105, P<.05), consistent with breakdown of the blood-brain barrier. Diffusion MRI revealed a strong trend towards globally decreasing diffusion coefficients at 24 and 72 hours (P=0.14), consistent with widespread cell death. In our model of CA, global IR results in poor neurological function and global injury by MRI that is not reflected by early histology. MRI thus appears to be a more sensitive measure of visualizing neurological injury in the early stages after CA and may predict the delayed neuronal death remarked upon by other authors.

Abstract P15: Periodic Acceleration (pGz) Preconditioning in Swine Increases Endothelial Derived NO and Phosphorylated eNOS via Akt Pathway

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jose A Adams ◽  
Jaqueline Arias ◽  
Jorge Bassuk ◽  
Heng Wu ◽  
Arkady Uryash ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Myocardial Stunning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Spontaneous Circulation ◽  
Akt Pathway ◽  
Phosphorylated Akt ◽  
Manual Chest Compression ◽  
Periodic Acceleration ◽  
Pulsatile Shear Stress

Periodic acceleration (pGz) is the motion of the supine body using a motorized platform (3Hz & ±0.4G). pGz produces pulsatile shear stress increasing release of endothelial derived NO (eNO) which, also decreases myocardial stunning and improves outcomes from ventricular fibrillation (VF) cardiac arrest. Preconditioning with pGz (PRE-pGz) prior to VF cardiac arrest ameliorates global post resuscitation cardiac dysfunction and reduces arrhythmias. To test whether pGz and PRE-pGz increase eNOS and phosphorylated eNOS (p-eNOS) via the PI3-kinase-Akt pathway, anesthetized, intubated male swine (40 –50lbs) were studied. Five animals had no intervention (BL) and 5 received 1 hr pGz preconditioning (pGz) followed by Western Blot of myocardial tissue. Additional animals (10 per group) received 1 hr pGz (PRE-pGz) or no treatment (CPR-CONT). In the latter groups VF was electrically induced and unsupported for 8 min followed by continuous manual chest compression and defibrillation for 10 min or until return of spontaneous circulation (ROSC). PRE-pGz animals showed less hemodynamically significant arrhythmias after ROSC than CPR-CONT (35 vs 7; p<0.05) and less myocardial stunning. eNOS and phosphorylated-eNOS (p-eNOS) significantly increased after pGz and after CPR but were significantly higher in pGz preconditioned animals along with increased phosphorylated Akt (p-Akt). The graph below shows % changes relative to BL (M±SD). *p < 0.01 PRE-pGz vs CPR-CONT. Conclusion: pGz applied prior to ischemia reperfusion injury increases eNOS and p-eNOS expression and increased p-Akt. Thus, pGz preconditioning protects myocardium during I-R in part by activating eNOS through p-Akt

Abstract 10773: Curcumin Improves the Outcomes of Cardiopulmonary Resuscitation in a Rat Model of Cardiac Arrest

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Zhengfei Yang ◽  
Jiangang Wang ◽  
Lu Yin ◽  
Shen Zhao ◽  
Ziren Tang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Placebo Group ◽  
Rat Model ◽  
Myocardial Function ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Sprague Dawley ◽  
Successful Resuscitation ◽  
Pre Treatment

Introduction: Curcumin has been proven to provide potent protection of vital organs against regional ischemia reperfusion injury. In this study, we investigated the effects of curcumin on the outcomes of CPR in a rat model of cardiac arrest. Hypothesis: Curcumin reduces the severity of post-CPR myocardial dysfunction and prolong the duration of survival. Method: Sixteen male Sprague-Dawley rats weighing between 450-550g were randomized into two groups: 1) Placebo; 2) Curcumin (100 mg/kg) pre-treatment. Ventricular fibrillation (VF) was induced. After 8 mins of VF, CPR was initiated for 8 mins and defibrillation was then attempted. Myocardial function was measured by echocardiography at baseline and hourly for 4 hours following successful resuscitation. The duration of survival was observed for total 72 hours. Result: Six animals in the placebo group and seven in the curcumin group were successfully resuscitated. Post-resuscitation myocardial function was significantly impaired in all animals. However, myocardial function gradually improved 4 hours after resuscitation and was significantly better in the animals pre-treated with curcumin (Figure). Significantly shorter duration of survival of 40±29 hours was observed in the placebo group. Conclusion: In a rat model of cardiac arrest, curcuminim proves post-resuscitation myocardial dysfunction and prolongs the duration of survival.

Potent Therapy and Transcriptional Profile of Combined Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in mice

2020 ◽  
Author(s):  
Yuanyuan Wu ◽  
Weiwei Chen ◽  
Yufang Zhang ◽  
Aifen Liu ◽  
Cheng Yang ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Early Stage ◽  
Synergistic Effects ◽  
Ischemia Reperfusion ◽  
Combined Treatment ◽  
Specific Treatment ◽  
Transcriptional Profile ◽  
Apoptosis And Inflammation ◽  
Active Caspase

Abstract Cause-specific treatment and timely diagnosis are still not available for acute kidney injury (AKI) apart from supportive therapy and serum creatinine measurement. A novel erythropoietin-derived cyclic helix B surface peptide (CHBP) protects kidneys against AKI with different causes, but the underlying mechanism is not fully defined. Herein, we investigated the transcriptional profile of renoprotection induced by CHBP and its potential synergistic effects with siRNA targeting caspase-3, an executing enzyme of apoptosis and inflammation, (CASP3siRNA) on ischemia/reperfusion (IR)-induced AKI. Utilizing a mouse model with 30-min renal bilateral ischemia and 48-h reperfusion, the renoprotection of CHBP or CASP3siRNA was demonstrated in renal function and structure, active caspase-3 and HMGB1 expression. Combined treatment of CHBP and CASP3siRNA further preserved kidney structure, and reduced active caspase-3 and HMGB1. Furthermore, differentially expressed genes (DEGs) were identified with fold change > 1.414 and P < 0.05. In IR kidneys, 281 DEGs induced by CHBP were mainly involved in promoting cell division and improving cellular function and metabolism (up-regulated STAT5B and SLC22A7). The additional administration of CASP3siRNA caused 504 and 418 DEGs in IR + CHBP kidneys with or without NCsiRNA, with 37 genes in common. These DEGs were associated with modulated apoptosis and inflammation (up-regulated BCL6, SLPI and SERPINA3M), and immunity, injury and microvascular homeostasis (up-regulated CFH and GREM1, and down-regulated ANGPTL2). This proof-of-effect study indicated the potent renoprotection of CASP3siRNA upon CHBP at the early stage of IR-induced AKI. Underlying genes, BCL6, SLPI, SERPINA3M, GREM1 and ANGPTL2, might be potential new biomarkers for clinical applications.

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