M1 macrophage-derived exosomes inhibit cardiomyocyte proliferation through delivering miR-155.

BACKGROUND: M1 macrophages are closely associated with cardiac injury after myocardial infarction (MI). Increasing evidence shows that exosomes play a key role in pathophysiological regulation after MI, but the role of M1 macrophage-derived exosomes (M1-Exos) in myocardial regeneration remains unclear. In this study, we explored the impact of M1 macrophage-derived exosomes on cardiomyocytes regeneration in vitro and in vivo. METHODS: M0 macrophages were induced to differentiate into M1 macrophages with GM-CSF (50 ng/mL) and IFN-γ (20 ng/mL). Then M1-Exos were isolated and co-incubated with cardiomyocytes. Cardiomyocyte proliferation was detected by pH3 or ki67 staining. Quantitative real-time PCR (qPCR) was used to test the level of miR-155 in macrophages, macrophage-derived exosomes and exosome-treated cardiomyocytes. MI model was constructed and LV-miR-155 was injected around the infarct area, the proliferation of cardiomyocytes was counted by pH3 or ki67 staining. The downstream gene and pathway of miR-155 were predicted and verified by dual-luciferase reporter gene assay, qPCR and immunoblotting analysis. IL-6 (50 ng/mL) was added to cardiomyocytes transfected with miR-155 mimics, and the proliferation of cardiomyocytes was calculated by immunofluorescence. The protein expressions of IL-6R, p-JAK2 and p-STAT3 were detected by Western blot. RESULTS: The results showed that M1-Exos suppressed cardiomyocytes proliferation. Meanwhile, miR-155 was highly expressed in M1-Exos and transferred to cardiomyocytes. miR-155 inhibited the proliferation of cardiomyocytes and antagonized the pro-proliferation effect of interleukin 6 (IL-6). Furthermore, miR-155 targeted gene IL-6 receptor (IL-6R) and inhibited the Janus kinase 2(JAK)/Signal transducer and activator of transcription (STAT3) signaling pathway. CONCLUSION: M1-Exos inhibited cardiomyocyte proliferation by delivering miR-155 and inhibiting the IL-6R/JAK/STAT3 signaling pathway. This study provided new insight and potential treatment strategy for the regulation of myocardial regeneration and cardiac repair by macrophages.

Effect of Clemastine Fumarate on Perioperative Hemodynamic Instability Mediated by Anaphylaxis During Cardiopulmonary Bypass Surgery.

BACKGROUND Perioperative hemodynamic instability mediated by anaphylaxis is a life-threatening complication in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to evaluate the effect of clemastine fumarate in this specific patient population. MATERIAL AND METHODS We enrolled 100 participants who met the inclusion criteria and randomly allocated them to the treatment group and the placebo group. Participants in the treatment group and the placebo group were treated separately with an injection of clemastine fumarate and saline, respectively. Plasma histamine concentration and blood pressure were quantified at 5 timepoints during the perioperative period, and differences between the 2 groups were assessed by repeated-measures ANOVA. The postoperative complications and in-hospital mortality also were evaluated. All participants were followed up for 7 days after cardiac surgery. RESULTS Plasma histamine concentrations increased in both groups but were statistically significantly lower in the treatment group during the perioperative period (P=0.007). Diastolic blood pressure (P=0.014) and mean arterial pressure (P=0.024) in the treatment group were significantly higher than in the placebo group during the perioperative period. The coefficients of variation for systolic (13.9±4.2% vs 17.2±4.4%, P<0.01) and diastolic (12.9±4.9% vs 15.3±5.2%, P=0.02) blood pressure were significantly lower in the treatment group compared with the placebo group. CONCLUSIONS Pretreatment with clemastine fumarate restrains the increase in histamine concentration and provides safer hemodynamics in patients undergoing cardiac surgery with CPB.

Mir-455-3p-1 represses FGF7 expression to inhibit pulmonary arterial hypertension through inhibiting the RAS/ERK signaling pathway.

OBJECTIVE: To analyze the effects of miR-455-3p-1 and its possible mechanisms in pulmonary arterial hypertension (PAH). METHODS: A microarray assay was used to examine the expressed genes between normal and PAH. The expressed genes in PAH was assessed by qRT-PCR. The targeted interaction between miRNAs and FGF7 was confirmed using a dual luciferase reporter assay. A CCK-8 assay and cell count were used to analyze the pulmonary artery smooth muscle cells (PASMCs) activity and proliferation level, respectively. Apoptotic PASMCs were detected by flow cytometry. In addition, the mRNA and protein expression levels of RAS/ERK signaling pathway were determined by qRT-PCR and a Western blot assay, respectively. A PAH rat model was used to identify the effects of miR-455-3p-1 in vivo. RESULTS: FGF7 was upregulated in PAH. MiR-455-3p-1 was downregulated in PAH. MiR-455-3p-1 targeted FGF7. MiR-455-3p-1 decreased the expression of FGF7. Moreover, the effect of FGF7 on PASMCs was suppressed by miR-455-3p-1. MiR-455-3p-1 upregulation was associated with reduced mRNA and protein levels of core RAS/ERK signal genes, suggesting the inhibition of the RAS/ERK pathway. Furthermore, miR-455-3p-1 upregulation improved the RVSP, mPAP, ratio of RV/LV + S, CO and RV function of PAH rat model in vivo. CONCLUSION: Our findings illustrate a role for miR-455-3p-1 in modulating FGF7-RAS/ERK signaling and suggest that an agomir of miR-455-3p-1 could inhibit the proliferation of PASMCs and mitigate PAH in vivo.

Long non-coding RNA CASC2 suppresses pulmonary artery smooth muscle cell proliferation and phenotypic switch in hypoxia-induced pulmonary hypertension.

BACKGROUND: In this study, we aimed to investigate whether and how lncRNA CASC2 was involved in hypoxia-induced pulmonary hypertension (PH)-related vascular remodeling. METHODS: The expression of lncRNAs or mRNAs was detected by qRT-PCR, and western blot analysis or immunochemistry was employed for detecting the protein expression. Cell number assay and EdU (5-ethynyl-2'-deoxyuridine) staining were performed to assess cell proliferation. Besides, flow cytometry and wound healing assay were employed for assessments of cell apoptosis and cell migration, respectively. Rat model of hypoxic PH was established and the hemodynamic measurements were performed. Hematoxylin and eosin (HE) and Masson's trichrome staining were carried out for pulmonary artery morphometric analysis. RESULTS: The expression of lncRNA CASC2 was decreased in hypoxia-induced rat pulmonary arterial tissues and pulmonary artery smooth muscle cells (PASMCs). Up-regulation of lncRNA CASC2 inhibited cell proliferation, migration yet enhanced apoptosis in vitro and in vivo in hypoxia-induced PH. Western blot analysis and immunochemistry showed that up-regulation of lncRNA CASC2 greatly decreased the expression of phenotype switch-related marker α-SMA in hypoxia-induced PH. Furthermore, it was indicated by the pulmonary artery morphometric analysis that lncRNA CASC2 suppressed vascular remodeling of hypoxia-induced rat pulmonary arterial tissues. CONCLUSION: LncRNA CASC2 inhibited cell proliferation, migration and phenotypic switch of PASMCs to inhibit the vascular remodeling in hypoxia-induced PH.

Effects of Ulinastatin on In Vitro Storage Lesions of Human Red Blood Cells.

BACKGROUND: The study aimed to investigate the influence of in vitro storage on erythrocyte complement receptor one (E-CR1), cell shrinkage and eryptosis of human red blood cells (RBCs), and to assess the possible effects of ulinastatin (UTI) on them. METHODS: After collection, RBCs were treated with saline (control group) and different concentrations of UTI (5,000 U/mL, 10,000 U/mL, and 50,000 U/mL in Group C1, Group C2, and Group C3, respectively). E-CR1, cell size, and phosphatidylserine (PS) exposure and intracellular Ca2+ concentration were analyzed by flow cytometer every 7 days up to Day 35. RESULTS: E-CR1 level and cell size of all groups decreased during storage. In the control group, E-CR1 began to decrease on Day 28 and cells shrank on Day 21. The E-CR1 level of Group C2 was significantly higher than that of the control group beginning on Day 21. The cells of Group C1 and Group C2 began to shrink remarkably on Day 21, and those of Group C3 on Day 35. PS-exposure levels of 4 groups started to increase on Day 7 (p < 0.05), while from Day 14 to 35 those of Group C3 were significantly lower than the control group (p < 0.05). The intracellular Ca2+ levels of the control group started to increase significantly on Day 7, one week earlier than the experimental groups. From Day 21 to 35, the intracellular Ca2+ levels of Group C2 and C3 were significantly lower than those of the control group (p < 0.05). CONCLUSIONS: RBCs underwent E-CR1 loss, cell shrinkage, and eryptosis during in vitro storage, which could be attenuated by UTI.

Age-associated differences in response to sevoflurane postconditioning in rats.

BACKGROUND: Experimental evidence suggests that anesthetic preconditioning and postconditioning could effectively attenuate myocardial ischemia/reperfusion (I/R) injury. In this study, we aimed at investigating whether there are age-associated differences in response to sevoflurane postconditioning during myocardial I/R injury in young and old rats, and explore the underlying molecular mechanisms. METHODS: Young and old rats were subjected to 30 min myocardial ischemia, followed by 2 h of reperfusion, with or without sevoflurane postconditioning. RESULTS: Both 1 and 2 minimal aveolar concentration (MAC) sevoflurane postconditioning reduced infarct size (IS) (34 ± 3% and 32 ± 2% vs. 58 ± 5%, p < 0.05) and apoptotic index (8 ± 1% and 7 ± 1% vs. 15 ± 2%, p < 0.05) in young rats, compared to young control group. In contrast, they could not reduce IS (45 ± 3% and 43 ± 3% vs. 47 ± 3%, p > 0.05) and apoptotic index (28 ± 3% and 25 ± 2%, vs. 26 ± 2%, p > 0.05) in old rats, compared to old control group. Mechanistically, we found that the phosphorylation of both Akt and ERK1/2 but not STAT3 was substantially enhanced after sevoflurane postconditioning in young rats, compared to young control group, but not in old rats, relative to old control group. CONCLUSION: There are age-related differences after exposure to sevoflurane postconditioning that protects young, but not old rat hearts against I/R injury, which may be at least associated with the inability to activate Akt and ERK1/2.

A Novel Combined-Catheter to Monitor Left and Right Atrial Pressures: A Simple and Reliable Method for Pediatric Cardiac Surgery.

OBJECTIVE: To introduce a novel combined-catheter to monitor left and right atrial pressures. DESIGN: Prospective observational study. SETTING: Fuwai Hospital, China. PATIENTS: A total of 113 pediatric patients (77 men), median age 10.3 months, admitted between July 10, 2014, and February 5, 2015, were divided into two groups: the novel-catheter group and the traditional-method group. INTERVENTIONS: All patients received routine anesthesia and surgery. Left atrial pressure and central venous pressure (an estimate of right atrial pressure), measured through a catheter needle during surgery, were identified as the "gold standard." A novel combined-catheter, composed of a reformed triple-lumen catheter with a microtube inserted within its central cavity, was used in the novel-catheter group. A traditional triple-lumen catheter to monitor central venous pressure plus another single-lumen catheter to monitor left atrial pressure were used in the traditional-method group. MEASUREMENTS AND MAIN RESULTS: The novel combined-catheter could accurately monitor left atrial pressure and central venous pressure. Pressure values measured by the novel catheter correlated well with the gold standard (left atrial pressure, R = 0.98; central venous pressure, R = 0.99). Bland-Altman analyses revealed good agreement between pressures measured by the novel catheter and the gold standard. The absolute value of maximum difference was 0.67 mm Hg for left atrial pressure and 0.33 mm Hg for central venous pressure, which are acceptable in clinical practice. Left atrial pressure-monitoring catheter displaced into the right atrium occurred significantly less frequently in the novel-catheter group when compared with the traditional-method group (5 and 12 cases, respectively). CONCLUSIONS: This novel combined-catheter was safe and reliable at monitoring left and right atrial pressures, and infusion involved only one catheter without the disadvantages of the traditional method. This new novel method may be particularly useful in pediatric open-heart surgery.

Comparison of cardio-protective effects induced by different modalities of sevoflurane conditioning in isolated rat hearts.

OBJECTIVE: To examine whether the combination of anesthetic preconditioning and anesthetic postconditioning could elicit additional cardio-protection as compared to either anesthetic preconditioning or anesthetic postconditioning alone and its underlying mechanism. METHODS: Isolated rat hearts were randomized into one of four groups: CTRL group (30 min of ischemia followed by 120 min of reperfusion alone); SpreC group (3% sevoflurane preconditioning was administered for 15 min followed by 10 min of washout before ischemia); SpostC group (3% sevoflurane postconditioning was administered during the first 15 min of reperfusion after ischemia); SpreC+SpostC group (the protocols of SpreC and SpostC were combined). Hemodynamics, myocardial infarct size, lactate dehydrogenase and creatine kinase-MB in collected effluent, phosphorylation of PKB/Akt and ERK 1/2 and content of nicotinamide adenine dinucleotide in the left ventricular tissue were compared among the four groups. RESULTS: When compared with unprotected Control hearts, those in the sevoflurane-treated groups (SpreC, SpostC and SpreC+SpostC) showed significantly better functional recovery, reduced myocardial infarct size and decreased lactate dehydrogenase and creatine kinase-MB release. Comparison of the above-mentioned variables among the three sevoflurane-treated groups showed that maximal cardio-protection was obtained in the SpreC+SpostC group. Both SpreC and SpreC+SpostC induced a biphasic response in protein kinase B (PKB/Akt) and extracellular signal-regulated kinase (ERK 1/2) phosphorylation, while SpostC induced only one phase. The effects on phosphorylation of both PKB/Akt and ERK 1/2 induced by SpreC and SpostC were found to be additive during reperfusion. The combination of SpreC and SpostC also had additive effects on inhibiting mitochondrial permeability transition pore (mPTP) opening induced by ischemia-reperfusion. CONCLUSION: These findings suggested that the cardio-protection induced by SpreC and SpostC could be additive via the involvement of PKB/Akt, ERK 1/2 and mPTP.

Delayed remote preconditioning induces cardioprotection: role of heme oxygenase-1.

BACKGROUND: The role of heme oxygenase-1 (HO-1) in the cardioprotection induced by delayed remote ischemic preconditioning (DRIPC) has not been investigated. Therefore, this study was designed to investigate whether HO-1 is involved in DRIPC-mediated cardioprotection in an isolated perfused rat heart model. MATERIALS AND METHODS: Isolated rat hearts were subjected to 30 min ischemia followed by 60 min reperfusion. DRIPC (four cycles 5-min occlusion and 5-min reflow at the unilateral hind limb once per day for 1, 2, or 3 d before heart isolation, abbreviated as D1RIPC, D2RIPC, or D3RIPC respectively). Infarct size, myocardial troponin levels, and heart function were measured. The protein and messenger RNA levels of HO-1 were determined. RESULTS: DRIPC facilitated postischemic cardiac functional recovery and decreased cardiac enzyme release. The infarct size-limiting effect of DRIPC was more pronounced in the D3RIPC group (10.22 ± 2.57%) than the D1RIPC group (22.34 ± 4.02%, P < 0.001) or the D2RIPC group (14.60 ± 3.13%, P = 0.034). These effects in the D1RIPC group could be blocked by Zinc Protoporphyrin IX (ZnPP) (an HO-1 specific inhibitor). DRIPC-mediated cardioprotection was associated with enhanced HO-1 protein expression (D1RIPC, 0.11 ± 0.03; versus 0.15 ± 0.06 in the D2RIPC group, P = 0.06; versus 0.20 ± 0.04 in the D3RIPC group, P = 0.04) and messenger RNA levels of HO-1 expression. CONCLUSIONS: Our findings suggest that HO-1 is involved in the cardioprotection induced by DRIPC, and that increase in the number of preconditioning stimuli may enhance cardioprotective effects accompanied with increased HO-1 level.

Restoration of autophagic flux in myocardial tissues is required for cardioprotection of sevoflurane postconditioning in rats.

AIM: Sevoflurane postconditioning (SpostC) has been shown to protect the heart from ischemia-reperfusion (I/R) injury. In this study, we examined whether SpostC affected autophagic flux in myocardial tissues that contributed to its cardioprotective effects in rats following acute I/R injury. METHODS: SD rats underwent 30 min of left anterior descending coronary artery ligation followed by 120 min of reperfusion. The rats were subjected to inhalation of 2.4% (v/v) sevoflurane during the first 5 min of reperfusion, and chloroquine (10 mg/kg, ip) was injected 1 h before I/R. Myocardial infarct size was estimated using TTC staining. Autophagosomes in myocardial tissues were detected under TEM. Expression of LC3B-II, beclin-1, p62/SQSTM1, cathepsin B, caspase-3 and cleaved PARP was assessed using Western blot analysis. Plasma cardiac troponin I was measured using ELISA. Cardiomyocyte apoptosis was evaluated with TUNEL staining. RESULTS: I/R procedure produced severe myocardium infarct and apoptosis accompanied by markedly increased number of autophagosomes, as well as increased levels of LC3B-II, beclin-1 and p62 in myocardial tissues. SpostC significantly reduced infarct size, attenuated myocardial apoptosis, restored intact autophagic flux and improved the lysosomal function in myocardial tissues. Administration of chloroquine that blocked autophagic flux abrogated the cardioprotective effects of SpostC. CONCLUSION: SpostC exerts its cardioprotective effects in rats following I/R injury via restoring autophagic flux in myocardial tissues.

[Effects of multidisciplinary blood management strategy on transfusion and outcomes in patients undergoing valvular heart surgery].

UNLABELLED: To evaluate the effect of multidisciplinary blood management strategy in adults patients undergoing valvular heart surgery. METHODS: A multidisciplinary patient blood management (PBM) strategy was instituted in Fuwai Hospital since January 2009. It includes Establishment of a multidisciplinary blood transfusion management team and designation of a coordinator; Enactment perioperative transfusion triggers (Hb < 80 g/L) for adults patients undergoing cardiac surgery; recommendation of antifibrinolytics, cell salvage, reduced cardiopulmonary bypass circuit; setting up Blood Consumption Announcement and Scoring System, which regularly publishes notifications of blood volume consumed per case, per single procedure and per surgeon. Clinical date before and after multidisciplinary patient blood management strategy will be presented. RESULTS: A total of 3 951 consecutive patients underwent Valvular Heart Surgery were analyzed. 1 713 cases were in pre-PBM group, and 2 238 cases were in post-PBM group. Both incidence and average units of allogeneic red blood cell transfusion perioperatively in post-PBM group were decreased (28.5% vs 75.3%, P = 0.000, and 1.2 U vs 4.0 U, P = 0.000). The postoperative length of stay in hospital and incidence of pneumonia were reduced in post-PBM group (8.2 d vs 10.5 d, P = 0.02, and 2.7% vs 3.5%, P = 0.04). The post-PBM group had lower in-hospital mortality (0.6% vs 1.2%, P = 0.000). CONCLUSION: Multidisciplinary patient blood management strategy significantly reduced blood transfusion, morbidity and mortality in patients underwent valvular heart surgery. It save plenty of blood resources.

Rhodopseudomonas palustris shapes bacterial community, reduces Cd bioavailability in Cd contaminated flooding paddy soil, and improves rice performance.

Photosynthetic bacteria (PSB) are suitable to live and remediate cadmium (Cd) in the slightly oxygenated or anaerobic flooding paddy field. However, there is currently limited study on the inhibition of Cd accumulation in rice by PSB, and the relevant mechanisms has yet to be elucidated. In the current study, we firstly used Rhodopseudomonas palustris SC06 (a typical PSB) as research target and combined physiology, biochemistry, microbiome and metabolome to evaluate the mechanisms of remeding Cd pollution in paddy field and inhibiting Cd accumulation in rice. Microbiome analysis results revealed that intensive inoculation with R. palustris SC06 successfully survived and multiplied in flooding paddy soil, and significantly increased the relatively abundance of anaerobic bacteria including Desulfobacterota, Anaerolineaceae, Geobacteraceae, and Gemmatimonadaceae by 46.40 %, 45.00 %, 50.12 %, and 21.30 %, respectively. Simultaneously, the structure of microbial community was regulated to maintain relative stability in the rhizosphere soil of rice under Cd stress. In turn, these bacteria communities reduced bioavailable Cd and enhanced residual Cd in soil, and induced the upregulation of sugar and organic acids in the rice roots, which further inhibited Cd uptake in rice seedlings, and dramatically improved the photosynthetic efficiency in the leaves and the activities of antioxidative enzymes in the roots. Finally, Cd content of the roots, stems, leaves, and grains significantly decreased by 38.14 %, 69.10 %, 83.40 %, and 37.24 % comparing with the control, respectively. This study provides a new strategy for the remediation of Cd-contaminated flooding paddy fields and the safe production of rice.

ß-blockers and volatile anesthetics may attenuate cardioprotection by remote preconditioning in adult cardiac surgery: a meta-analysis of 15 randomized trials.

OBJECTIVE: Clinical trials on cardioprotection by remote ischemic preconditioning (RIPC) for adult patients undergoing cardiac surgery revealed mixed results. Previous meta-analyses have been conducted and found marked heterogeneity among studies. The aim of this meta-analysis was to evaluate the factors affecting cardioprotection by remote preconditioning in adult cardiac surgery. DESIGN: A meta-analysis of randomized controlled trials. SETTING: University hospitals. PARTICIPANTS: Adult subjects undergoing cardiac surgery. INTERVENTIONS: RIPC. MEASUREMENTS AND MAIN RESULTS: Fifteen trials with a total of 1,155 study patients reporting postoperative myocardial biomarker (CK-MB or troponin) levels were identified from PubMed, Embase, and the Cochrane Library (up to July 2012). Compared with controls, RIPC significantly reduced postoperative biomarkers of myocardial injury (standardized mean difference = -0.31, p = 0.041; heterogeneity test: I(2) = 83.5%). This effect seemed more significant in valve surgery (standardized mean difference = -0.74, p = 0.002) than in coronary artery surgery (standardized mean difference = -0.23; p = 0.17). Univariate meta-regression analyses suggested that the major sources of significant heterogeneity were ß-blockers (%) (coefficient = 0.0161, p = 0.022, adjusted R(2) = 0.37) and volatile anesthetics (coefficient = 0.6617, p = 0.065, adjusted R(2) = 0.22). These results were further confirmed in multivariate regression and subgroup analyses. CONCLUSIONS: Available data from this meta-analysis further confirmed the cardioprotection conferred by RIPC in adult cardiac surgery. Moreover, the cardioprotective effect may be attenuated when combined with ß-blockers or volatile anesthetics.

Ulinastatin as a neuroprotective and anti-inflammatory agent in infant piglets model undergoing surgery on hypothermic low-flow cardiopulmonary bypass.

OBJECTIVE: Infants are potentially more susceptible to brain injury mediated via cell death attributed to cardiopulmonary bypass (CPB) especially with prolonged hypothermic low flow (HLF). We hypothesized that a human urinary protease inhibitor (ulinastatin), by its anti-inflammatory effect, would reduce central nervous system (CNS) injury during HLF. METHODS: Fifteen general-type infant piglets were randomized to ulinastatin group (group U, n = 5), control group (group C, n = 5), and sham operation group (group S, n = 5). Routine CPB was established after median thoracotomy in group U and C under anesthesia. When the temperature of infant piglets dropped down to 25 °C, low-flow CPB (50 ml·kg(-1) ·min(-1) ) was instituted. After 120 min of aortic cross-clamping and 20- to 30-min rewarming, the aortic cross-clamp was removed and finally the piglet was weaned from CPB. Five thousand units per killogram of ulinastatin and equivalently normal saline were, respectively, given at the beginning of and at aortic declamping in group U and group C. group S just received sham median thoracotomy. Venous blood samples were taken immediately after anesthesia induction in all three groups, 5- and 120-min post CPB in both group U and C, respectively; plasma markers of inflammation and CNS injury were compared. Pathology results of hippocampus were observed by light microscopy. RESULTS: Statistically significant differences between group C and U were noted in the expression of inflammatory markers such as IL-10, TNF-α and neuron-specific enolase at 120-min post CPB. Brain injuries were observed in both groups (index cases and controls) and were milder in group U. CONCLUSIONS: In our study, HLF CPB on infant piglets resulted in brain injury, and ulinastatin might reduce the extent of such injury.

Stenting technique, gender, and age are associated with cardioprotection by ischaemic postconditioning in primary coronary intervention: a systematic review of 10 randomized trials.

AIMS: We sought to perform a systematic review and meta-analysis to evaluate the potential factors affecting ischaemic postconditioning (IPoC) for patients with ST-segment elevation acute myocardial infarction (STEMI) in primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: Ten randomized controlled trials (RCTs) on IPoC reporting myocardial enzyme levels or left ventricular ejection fraction (LVEF) in a total of 560 STEMI patients were identified in PubMed, EMBase, and Cochrane Library (up to February 2012). Compared with controls, IPoC significantly reduced elevated cardiac enzyme levels [standardized mean difference = -0.84; 95% confidential interval (CI): -1.26 to -0.43; P < 0.00001; heterogeneity test, I(2) = 81.0%] and improved LVEF [weighted mean difference (WMD) = 3.98%; 95% CI: 1.27-6.70%; P = 0.004; heterogeneity test, I(2) = 87.1%]. The effect on LVEF remained significant after 1 year (WMD = 5.04%; 95% CI: 4.20-5.88%; P < 0.00001; heterogeneity test, I(2) = 0.0%). Univariate meta-regression analysis suggested that the major sources of significant heterogeneity (P < 0.1) were the use of direct-stenting technique (%) (coefficient = -0.886; P = 0.069; adjusted R(2) = 0.34) and male proportion (%) (coefficient = -0.022; P = 0.098; adjusted R(2) = 0.28) for myocardial enzyme levels, and age (coefficient = -1.34; P = 0.025; adjusted R(2)= 0.55) for LVEF (%). Subsequent multivariate regression and subgroup analysis confirmed these results. CONCLUSION: Available evidence from this systematic review and meta-analysis of 10 RCTs suggests that IPoC may confer cardioprotection in terms of myocardial enzyme levels and LVEF for STEMI during primary PCI. These effects are more pronounced among young and male patients, and those in whom direct-stenting techniques were used. Future studies should focus on the mortality in high-quality, large-scale clinical trials with long-term follow-up.

[Anesthetic management for patients undergoing total thoracoabdominal aorta replacement without cardiopulmonary bypass].

OBJECTIVE: To summarize the experience in anesthetic management for total thoracoabdominal aorta replacement without cardiopulmonary bypass. METHODS: From October 2009 to September 2010, 10 patients of Fuwai Hospital received off-pump total thoracoabdominal aorta replacement. Of these patients, 5 were subjected to Standford B aortic dissection, 2 were Standford A aortic dissection received total aortic arch replacement combined with transaortic stented graft implantation into the descending aorta.1 were Marfan's syndrome, and 2 were thoracoabdominal aorta. All operations used the technique which preserved blood was transfused back by pump via the femoral artery. RESULTS: The average surgery time was (7.4 ± 1.2) h and extubation time was (14.1 ± 2.5) h, the descending thoracic aorta cross clamp time was (11.5 ± 3.6) min, the intercostal artery reconstruction time was (16.4 ± 5.5) min, the required amount of blood products was fresh frozen plasma (600.5 ± 542.8) ml, platelet(1.7 ± 0.8) U, red blood cell (4.3 ± 2.4) U, auto blood salvage (465.7 ± 242.3) ml. Three patients occurred atelectasis and one patient occurred sero peritoneum postoperation. All of the 10 patients were discharged from hospital without any neurologic complications. CONCLUSION: The anesthetic management for total thoracoabdominal aorta replacement without cardiopulmonary bypass is feasible. It can reduce the side effects of deep hypothermia circulatory arrest and had a good effect.

[Effectiveness and safety of tranexamic acid in patients receiving on-pump coronary artery bypass grafting without clopidogrel and aspirin cessation].

OBJECTIVE: To evaluate the effectiveness and safty of tranexamic acid in patients receiving on-pump coronary artery bypass grafting (CABG) without clopidogrel and aspirin cessation. METHODS: The current study is a prospective, randomized and placebo-control trial. A total of 116 patients receiving selective on-pump CABG with their last ingestion of clopidogrle and aspirin within 7 days preoperatively were recruited. Despite 6 patients withdrawal their consent, the rest 110 were randomized to receive tranexamic acid or placebo. The tranexamic acid regimen was a bolus of 10 mg/kg followed by a maintenance of 10 mg·kg(-1)·h(-1) throughout the surgery. The primary outcome was the volume of allogeneic erythrocyte transfused perioperatively. RESULTS: Baseline characteristics were comparable between the groups. In patients receiving tranexamic acid and placebo respectively, the volume of allogeneic erythrocyte transfused was 4.0 (7.5) units and 6.0(6.0) units (W = 1021, P < 0.01). In these 2 groups respectively, blood loss was 930 (750) ml and 1210 (910) ml (W = 1042, P < 0.01), the incidence of major bleeding was 50.9% and 76.4% (χ(2) = 7.70, P < 0.01), the incidence of reoperation was 0 and 9.1% (χ(2) = 5.24, P = 0.02); the volume of plasma transfused was 400 (600) ml and 600 (650) ml (W = 1072, P = 0.01), the exposure of plasma was 60.0% and 85.5% (χ(2) = 8.98, P < 0.01) and the exposure to any allogeneic blood products was 85.5% and 98.2% (χ(2) = 5.93, P = 0.01). Perioperative mortality, morbidity and the incidence of adverse events were balanced between the groups without statistical significance. CONCLUSION: Tranexamic acid reduced significantly postoperative bleeding and transfusion in patients receiving on-pump CABG without clopidogrel and aspirin cessation.

Effects of Ulinastatin on Postoperative Renal Function in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass: A Prospective Cohort Study with 10-Year Follow-Up.

INTRODUCTION: The present study aimed to explore the potential effect of ulinastatin on renal function and long-term survival in patients receiving cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This prospective cohort study was conducted at Fuwai Hospital, Beijing, China. Ulinastatin was applied after induction anesthesia. The primary outcome was the rate of new-onset postoperative acute kidney injury (AKI). Moreover, a 10-year follow-up was conducted until January 2021. RESULTS: The rate of new-onset AKI was significantly lower in the ulinastatin group than in the control group (20.00 vs. 32.40%, p = 0.009). There was no significant difference in renal replacement therapy between the two groups (0.00 vs. 2.16%, p = 0.09). The postoperative plasma neutrophil gelatinase-associated lipocalin (pNGAL) and IL-6 levels were significantly lower in the ulinastatin group compared with the control group (pNGAL: p = 0.007; IL-6: p = 0.001). A significantly lower incidence of respiratory failure in the ulinastatin group compared with the control group (0.76 vs. 5.40%, p = 0.02). The nearly 10-year follow-up (median: 9.37, 95% confidence interval: 9.17-9.57) survival rates did not differ significantly between the two groups (p = 0.076). CONCLUSIONS: Ulinastatin significantly reduced postoperative AKI and respiratory failure in patients receiving cardiac surgery with CPB. However, ulinastatin did not reduce intensive care unit and hospital stays, mortality, and long-term survival rate.

The effect of sevoflurane postconditioning on cardioprotection against ischemia-reperfusion injury in rabbits.

Sevoflurane postconditioning is a potential clinical measure to protect myocardial. This experiment was designed to investigate the efficacy of sevoflurane postconditioning against ischemia-reperfusion injury. A total of 132 Japanese White Rabbits were enrolled into this study. They were underwent 15-, 30-, or 60-min left anterior descending coronary (LAD) artery occlusion, respectively. At the end of LAD artery occlusion, they randomly received a 5-min inhalation of air (control group), 1% sevoflurane (1% sev group), 2% sevoflurane (2% sev group), 4% sevoflurane (4% sev group) or an IV bolus injection of 5 mg/kg of NIM811 [a specific inhibitor of mitochondrial permeability transition pores (mPTP)]. Infarct size was determined after 2 h of reperfusion (triphenyltetrazolium chloride straining, percentage of risk area). The infarct sizes were significantly (P < 0.05) reduced after 15 min ischemia (5.5 ± 3.3%, 5.8 ± 3.6% vs. 20.3 ± 6.9% for 2% sev, 4% sev vs. control, respectively) and 30 min ischemia (23.5 ± 5.0%, 20.7 ± 5.9% vs. 50.9 ± 10.2%, for 2% sev, 4% sev vs. control, respectively; P < 0.05). However, it had no effect on infarct size after 60 min ischemia (64.1 ± 5.9%, 62.3 ± 7.6% vs. 72.7 ± 9.2% for 2% sev, 4% sev vs. control, respectively, P > 0.05).The efficacy of sevoflurane postconditioning gradually weakened with increasing ischemia duration and disappears after 60 min ischemia in rabbits in vivo.