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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.

The present study aimed to explore the protective effects of extracorporeal membrane oxygenation (ECMO) on intestinal mucosal injury following cardiopulmonary resuscitation (CPR), and to assess the potential mechanisms involved. A total of 24 healthy adult domestic pigs were selected as the study subjects. A ventricular fibrillation model was induced through programmed electric stimulation. Subsequently, the animals were randomly divided into conventional CPR and CPR+ECMO groups (n=12 per group). The mortality and hemodynamic parameters of the two groups were compared. The expression levels of inflammatory cytokines in the serum and intestinal mucosa were detected by ELISAs. The intestinal mucosa was subjected to hematoxylin and eosin, and immunohistochemical staining, followed by electron microscopy, to assess the degree of apoptosis and necrosis. The animals in both groups recovered from the programmed ventricular fibrillation. In the CPR group, two animals died at 2 h and two more animals died a further 2 h later, resulting in a 33.3% mortality rate, whereas no cases of mortality were observed in the CPR+ECMO group. Compared with the animals in the CPR group, the hemodynamic parameters of the animals in the CPR+ECMO group revealed significantly improved outcomes. Multiple inflammatory factors (tumor necrosis factor α, interleukin-1 and interleukin-6), myeloperoxidase and malondialdehyde levels were decreased, whereas Na/Ca-ATPase and superoxide dismutase levels were elevated in the intestinal mucosa of animals in the CPR+ECMO group compared with those in the CPR group. Additionally, pathological staining demonstrated that the intestinal mucosa tissue in the CPR+ECMO group exhibited less apoptosis, necrosis and inflammatory cell infiltration, which was further supported by a decrease in Bax expression and an increase in Bcl-2 expression. Overall, ECMO after CPR reduced the intestinal mucosal barrier injury after spontaneous circulation recovery, and the mechanism involved decreased inflammation and apoptosis.

Introduction Despite decades of improved strategy in conventional cardiopulmonary resuscitation (CCPR), survival rates of favorable neurological outcome after cardiac arrest (CA) remains poor. It is indicated that the survival rate of successful resuscitation of extracorporeal membrane oxygenation (ECMO) is superior to that of CCPR. But the effect of ECMO in heart is unclear. We aimed to investigate whether ECMO produces cardiac protection by ameliorating post-ischemia reperfusion myocardial injury and myocardial apoptosis. Methods After undergoing 8-min untreated ventricle fibrillation (VF) and 6-min basic life support, 20 male pigs were ultimately used in this study and randomly divided into two groups: CCPR group (n = 10) and extracorporeal CPR (ECPR) group (n = 10). Hemodynamics and blood samples were obtained at baseline and 1, 2, 4, and 6 h during resuscitation. The successfully resuscitated pigs were sacrificed at 6 h after return of spontaneous circulation (ROSC), and the hearts were removed and analyzed under electron microscopy, and immunohistochemistry, quantitative real-time polymerase chain reaction, and immunofluorescence staining assay were performed to evaluate myocardial injury and myocardial apoptosis. Results There were no significant differences at basic hemodynamic status between the two groups. The survival rate of ECPR was significantly higher than CCPR group (10/10 [100%] vs. 4/10 [40%], P = 0.04). Compared to CCPR group, ECPR group exhibited a better outcome in hemodynamic function. Cardiac function was significantly impaired after ROSC in both groups, but left ventricular ejection fraction (LVEF) was significantly elevated in ECPR group than CCPR group. The expression of myocardial injury biomarkers (CK-MB, cTNI, H-FABP), endothelial injury biomarker (sP-selectin), and cardiac function biomarker (BNP) were remarkably increased after ROSC in both groups, but low levels in ECPR group than in CCPR group. Cardiomyocytes injury was attenuated in ECPR group under transmission electron microscopy (TEM). Typical apoptotic nuclei of cardiomyocytes were significantly reduced and oxidative damage were attenuated in ECPR group. Conclusions During prolonged VF-induced CA, ECPR contributes to improving hemodynamics, attenuating myocardial ischemia-reperfusion injury, ameliorating myocardial ultra structure, improving cardiac function, and elevating survival rate by preventing oxidative damage, regulating energy metabolism, inhibiting cardiomyocyte apoptosis. Electronic supplementary material The online version of this article (10.1186/s13049-019-0653-z) contains supplementary material, which is available to authorized users.

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-1β, IL-6, TNFα, and TGFβ, especially IL-1, IL-6, TNFα, and TGFβ, 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 TGFβ 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.

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

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. Key words: Acute Kidney Injury ; Cardiac Arrest; Cardiopulmonary Resuscitation; Extracorporeal Membrane Oxygenation; Swine