Protective effect of extracorporeal membrane pulmonary oxygenation combined with cardiopulmonary resuscitation on post-resuscitation lung injury.

BACKGROUND: Cardiac arrest (CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury. METHODS: Sixteen male swine were randomized to CCPR (CCPR; n=8; CCPR alone) and ECPR (ECPR; n=8; extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint. RESULTS: For the two groups, the survival rates between the two groups were not statistically significant (P>0.05), the blood and lung biomarkers were statistically significant (P<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant (P<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group. CONCLUSIONS: ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response post-resuscitation.

Establishment of Cattle Encephalon Glycoside and Ignotin Sustained-Release Drug Loading Nanostructured Lipid Carriers and Effect on the Repair Improving of Retinal Cells with Optic Nerve Injury.

The research aims to explore the preparation and physicochemical properties of cattle encephalon glycoside and ignotin (CEGI) sustained-release drug loading nanostructured lipid carriers (NLC) and to study the enhanced therapeutic efficacy of CEGI-NLC in treatment of retinal degenerative diseases, thereby providing an objective basis and guidance for clinical medication. The results showed that the particle size of drug-loaded microspheres was 333.2 nm and the potential was 24.9 MV, with an entrapment efficiency of (79±5.6)% and a drug loading efficiency of (7.76±2.3)%. The microspheres were spherical and evenly dispersed. The observations showed that drug-loaded microspheres had specific external sustained release characteristics compared with those of CEGI alone. CEGI-NLC can promote the activity of retinal cells. From the 7th to 28th day, the number of cell layers in the outer and inner nuclear layer retina decreased gradually. Electron microscopy observation showed that the apoptotic nuclear was deformed and the internal segment and cilia were broken down. After 14 and 28 days of CEGI-NLC treatment, the number of layers in the retina was thicker and the number of apoptotic cells was lower than those in the control group. The studies proved that CEGI-NLC has a positive effect on promoting the growth and the development of retinal cells as well as alleviating the process of retinal degeneration in RDS mice.

ECMO attenuates inflammation response and increases ATPase activity in brain of swine model with cardiac arrest compared with CCPR.

Extracorporeal membrane oxygenation (ECMO) could increase survival rate and neurological outcomes of cardiac arrest (CA) patients compared with conventional cardiopulmonary resuscitation (CCPR). Currently, the underlying mechanisms how ECMO improves neurological outcomes of CA patients compared with CCPR have not been revealed. A pig model of CA was established by ventricular fibrillation induction and then underwent CCPR or ECMO. Survival and hemodynamics during the 6 h after return of spontaneous circulation (ROSC) were compared. The levels of inflammatory cytokines and Ca2+-ATPase and NA+-K+-ATPase activities were detected. Brain tissues histology and ultra-microstructure in CCPR and ECMO groups were also examined. Results suggested that ECMO significantly improved the survival of pigs compared with CCPR. Heart rate (HR) decreased while cardiac output (CO) increased along with the time after ROSC in both ECMO and CCPR groups. At each time point, HR in ECMO groups was lower than that in CCPR group while CO and mean arterial pressure in ECMO group was higher than CCPR group. In ECMO group, lower levels of IL-1, IL-1ß, IL-6, TNFα, and TGFß, especially IL-1, IL-6, TNFα, and TGFß, were found compared that in CCPR group while no difference of IL-10 between the two groups was observed. Similar with the results from enzyme-linked immunosorbent assay, decreased expressions of IL-6 and TGFß were also identified by Western blotting. And Ca2+-ATPase and NA+-K+-ATPase activities were increased by ECMO compared with CCPR. Hematoxylin and eosin staining and ultra-microstructure examination also revealed an improved inflammation situation in ECMO group compared with CCPR group.

Extracorporeal Membrane Oxygenation Improving Survival and Alleviating Kidney Injury in a Swine Model of Cardiac Arrest Compared to Conventional Cardiopulmonary Resuscitation.

BACKGROUND: Acute kidney injury (AKI) frequently occurs in cardiopulmonary resuscitation patients. Studies comparing the effects of extracorporeal membrane oxygenation (ECMO) with conventional cardiopulmonary resuscitation (CCPR) on AKI were rare. This study aimed to compare the effects of ECMO with those of CCPR on survival rate and AKI and explore the underlying mechanisms in a swine model of cardiac arrest (CA). METHODS: Sixteen male pigs were treated with ventricular fibrillation to establish CA model and then underwent CCPR (CCPR group, n = 8) or ECMO during cardiopulmonary resuscitation (ECPR group, n = 8). The study endpoints were 6 h after return of spontaneous circulation (ROSC) or death. Serum and urine samples were collected at baseline and during the 6 h after ROSC. The biomarkers of AKI were detected by enzyme-linked immunosorbent assay. The apoptosis of renal tubular epithelial cells was discovered by transmission electron microscope (TEM) and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Apoptosis-related genes were detected by immune-staining and Western blotting. Data were compared by Student's t-test. RESULTS: All pigs in ECPR group were successfully resuscitated with a higher 6-h survival rate (8/8) compared to CCPR group (6/8). The expressions of AKI biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinase2 (TIMP2), insulin-like growth factor-binding protein 7 (IGFBP7), liver fatty acid-binding protein (LFABP), and kidney injury molecule1 (Kim-1) were all increased along with the time after ROSC in both groups and lower in ECPR group compared with CCPR group. Especially, products of urinary TIMP and IGFBP levels (TIMP*IGFBP) were significantly lower at ROSC4 (0.58 ± 0.10 ng2/ml2 vs. 1.18 ± 0.38 ng2/ml2, t = 4.33, P = 0.003) and ROSC6 (1.79 ± 0.45 ng2/ml2 vs. 3.00 ± 0.44 ng2/ml2, t = 5.49, P < 0.001); urinary LFABP was significantly lower at ROSC6 (0.74 ± 0.06 pg/ml vs. 0.85 ± 0.11 pg/ml, t = 2.41, P = 0.033); and urinary Kim-1 was significantly lower at ROSC4 (0.66 ± 0.09 pg/ml vs. 0.83 ± 0.06 pg/ml, t = 3.99, P = 0.002) and ROSC6 (0.73 ± 0.12 pg/ml vs. 0.89 ± 0.08 pg/ml, t = 2.82, P = 0.016). Under light microscope and TEM, the morphological injures in renal tissues were found to be improved in ECPR group. Moreover, apoptosis was also alleviated in ECPR group. CONCLUSIONS: Compared with CCPR, ECMO improves survival rate and alleviates AKI in a swine model of CA. The mechanism of which might be via downregulating AKI biomarkers and apoptosis in kidney.

Association of serum biomarkers with outcomes of cardiac arrest patients undergoing ECMO.

BACKGROUND: Recently, a series of studies have been conducted to investigate the association of the common biochemical biomarkers, such as serum lactate and creatinine, with clinical outcomes in cardiac arrest patients treated with extracorporeal membrane oxygenation (ECMO), however, the results were not consistent and the sample size of primary studies is limited. In the present study, we performed a systematic review and meta-analysis to summarize the associations. METHODS: Relevant studies in English databases (PubMed, ISI web of science, and Embase) and Chinese databases (Wanfang and CNKI) up to January 2018 were systematically searched. Crude ORs or HRs from the included studies were extracted and pooled to summarize the associations of lactate and creatinine with clinical outcomes including survival and neurological outcomes in ECMO treated cardiac arrest patients. RESULTS: 17 papers containing 903 cases were included in the present meta-analysis study. After pooling all the eligible studies, we identified the significant associations of high lactate level with poor survival (N=13, OR=1.335, 95%CI=1.167-1.527, P<0.001) and poor neurological outcome (N=2, HR=1.058, 95%CI=1.020-1.098, P=0.002) in CA patients treated with ECMO and a slight significant association of high creatinine with poor survival was also found (N=7, OR=1.010, 95%CI=1.002-1.018, P=0.015). CONCLUSIONS: High serum lactate level was associated with poor survival and poor neurological outcome in CA patients treated with ECMO. Further well-designed studies with larger sample size should be conducted to confirm the results.