龚俊松
中国医学科学院阜外医院 麻醉科
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.
Respiratory research 2019
OBJECTIVES:Acute kidney injury (AKI) is a prevalent complication after the surgical repair of paediatric cardiac defects and is associated with poor outcomes. Insufficient renal perfusion secondary to severe myocardial dysfunction in neonates is most likely an independent risk factor in patients undergoing repair for anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). We retrospectively investigated the epidemiology and outcomes of children with ALCAPA who developed AKI after repair.METHODS:Eighty-nine children underwent left coronary reimplantation. The paediatric-modified risk, injury, failure, loss and end-stage (p-RIFLE) criteria were used to diagnose AKI.RESULTS:The incidence of AKI was 67.4% (60/89) in our study. Among the patient cohort with AKI, 23 (38.3%) were diagnosed with acute kidney injury/failure (I/F) (20 with acute kidney injury and 3 with acute kidney failure). Poor cardiac function (left ventricular ejection fraction < 35%) prior to surgery was a significant contributing factor associated with the onset of AKI [odds ratio (OR) 5.55, 95% confidential interval (CI) 1.39-22.13; P = 0.015], while a longer duration from diagnosis to surgical repair (OR 0.97, 95% CI 0.95-1.00; P = 0.049) and a higher preoperative albumin level (OR 0.83, 95% CI 0.70-0.99; P = 0.041) were found to lower the risk of AKI. Neither the severity of preoperative mitral regurgitation nor mitral annuloplasty was associated with the onset of AKI. After reimplantation, there was 1 death in the no-AKI group and 2 deaths in the AKI/F group (P = 0.356); the remaining patients survived until hospital discharge. The median follow-up time was 46.5 months (34.0-63.25). During follow-up, patients in the AKI cohort were seen more often by specialists and reassessed more often by echocardiography.CONCLUSIONS:Paediatric AKI after ALCAPA repair occurs at a relatively higher incidence than that suggested by previous reports and is linked to poor clinical outcomes. Preoperative cardiac dysfunction (left ventricular ejection fraction < 35%) is strongly associated with AKI. The beneficial effect of delaying surgery seen in some of our cases warrants further investigation, as it is not concordant with standard teaching regarding the timing of surgery for ALCAPA.
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 2019
Aims: This study evaluated the efficacy and safety of tranexamic acid (TXA) undergoing cardiac surgery. Methods: Using a retrospective cohort study design, 2,026 consecutive pediatric patients who underwent surgical repair of atrial or ventricular septal defect or complete repair of Tetralogy of Fallot were included, and divided into a control group and a TXA group. Results: Compared with that in the control group, there were statistically significant reduction of both the 12-h and total postoperative blood loss in the TXA group [6.573 ± 0.144 vs. 5.499 ± 0.133 ml kg-1, mean difference (MD) 1.074 ml kg-1, p < 0.001; 12.183 ± 0.298 vs. 9.973 ± 0.276 ml kg-1, MD, 2.210 ml kg-1, p < 0.001]. There was a statistically significant reduction of the MD of 12-h postoperative blood loss due to TXA in patients aged < 1 year compared with that in patients aged ≥1 year (MD, 1.544 vs. 0.681 ml kg-1, P = 0.007). There were statistically significant reduction of the MD of both the 12-h and total postoperative blood loss due to TXA in patients weighing < 10 kg compared with that in patients weighing ≥10 kg (MD, 1.542 vs. 0.456 ml kg-1, P < 0.001, and MD, 2.195 vs. 0.929 ml kg-1, P = 0.036, respectively). There was a statistically significant reduction of the MD of total postoperative blood loss due to TXA in cyanotic patients compared with that in acyanotic patients (MD, 3.381 vs. 1.038 ml kg-1, P = 0.002). There was no significant difference in the postoperative volume or exposure of allogeneic transfusion, in-hospital morbidity or mortality between the groups. Conclusions: TXA took effects in reduction of postoperative blood loss but not the allogeneic transfusion requirement in pediatric patients undergoing cardiac surgery, particularly in infants weighing < 10 kg and cyanotic children. Moreover, the study suggested the use of TXA was safe in pediatric cardiac surgery.
Frontiers in pediatrics 2019
BACKGROUND:Postoperative bleeding remains a frequent complication after cardiovascular surgery and may contribute to serious morbidity and mortality. Observational studies have suggested a relationship between low endogenous plasma fibrinogen concentration and increased risk of postoperative blood loss in cardiac surgery. Although the transfusion of fibrinogen concentrate has been increasing, potential benefits and risks associated with perioperative fibrinogen supplementation in cardiovascular surgery are not fully understood.METHODS:PubMed, Cochrane Library, Ovid MEDLINE, Embase, Web of Science, and China National Knowledge Infrastructure were searched on January 15, 2017, with automated updates searched until February 15, 2018, to identify all randomized controlled trials (RCTs) of fibrinogen concentrate, whether for prophylaxis or treatment of bleeding, in adults undergoing cardiovascular surgery. All RCTs comparing fibrinogen infusion versus any other comparator (placebo/standard of care or another active comparator) in adult cardiovascular surgery and reporting at least 1 predefined clinical outcome were included. The random-effects model was used to calculate risk ratios and weighted mean differences (95% confidence interval [CI]) for dichotomous and continuous variables, respectively. Subgroup analyses by fibrinogen dose and by baseline risk for bleeding were preplanned.RESULTS:A total of 8 RCTs of fibrinogen concentrate in adults (n = 597) of mixed risk or high risk undergoing cardiovascular surgery were included. Compared to placebo or inactive control, perioperative fibrinogen concentrate did not significantly impact risk of all-cause mortality (risk ratio, 0.41; 95% CI, 0.12-1.38; I = 10%; P = .15). Fibrinogen significantly reduced incidence of allogeneic red blood cell transfusion (risk ratio, 0.64; 95% CI, 0.49-0.83; I = 0%; P = .001). No significant differences were found for other clinical outcomes. Subgroup analyses were unremarkable when analyzed according to fibrinogen dose, time of infusion initiation, mean cardiopulmonary bypass time, and rotational thromboelastometry/fibrinogen temogram use (all P values for subgroup interaction were nonsignificant).CONCLUSIONS:Current evidence remains insufficient to support or refute routine perioperative administration of fibrinogen concentrate in patients undergoing cardiovascular surgery. Fibrinogen concentrate may reduce the need for additional allogeneic blood product transfusion in cardiovascular surgery patients at high risk or with evidence of bleeding. However, no definitive advantage was found for reduction in risk of mortality or other clinically relevant outcomes. The small number of clinical events within existing randomized trials suggests that further well-designed studies of adequate power and duration to measure all-cause mortality, stroke, myocardial infarction, reoperation, and thromboembolic events should be conducted. Future studies should also address cost-effectiveness relative to standard of care.
Anesthesia and analgesia 2018
Objectives: Our aim was to retrospectively evaluate the benefit of levosimendan in certain complicated congenital heart procedures such as the pediatric anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) with moderate or severe cardiac dysfunction and its repair. Study Design: We enrolled 40 pediatric patients with ALCAPA and moderate or severe left ventricular dysfunction. Patients who had a preoperative left ventricular ejection fraction (LVEF) of 50% or less and had undergone the surgical correction of their coronary artery through cardiopulmonary bypass met the criteria of our study. Twenty patients were given 0.1-0.2 μg/kg/min levosimendan at the induction of anesthesia, which lasted for 24 h. The remaining 20 patients were not given levosimendan. Results: The mean preoperative LVEF in the levosimendan group was significantly lower than that in the non-levosimendan group (22.5 ± 10.7% vs. 31.8 ± 8.1%, p = 0.004). On postoperative day 7, the LVEF in the levosimendan group was still significantly lower (27.1 ± 8.9% vs. 37.5 ± 11.0%, p = 0.002). There was no significant difference in ΔLVEF detected on day 7 [median 30.8%, interquartile range (IQR) -4.4 to 63.5% vs. median 15.1%, IQR -3.5 to 40.0%, p = 0.560] or at follow-up of about 180 days (median 123.5%, IQR 56.1-222.6% vs. median 80.0%, IQR 36.4-131.3%, p = 0.064). There was no significant difference between the two groups in postoperative vasoactive-inotropic score (VIS) at any of the time points of 1, 6, 12, 24, and 48 h (p = 0.093). Three patients had to be supported by extracorporeal membrane oxygenation when difficulty appeared in weaning off cardiopulmonary bypass because of low cardiac output in the non-levosimendan group, but no patient needed extracorporeal membrane oxygenation after levosimendan infusion (p = 0.231). The length of intensive care unit stay (median 10.5 days, IQR 7.3-39.3 days vs. median 4.0 days, IQR 2.0-10.0 days, p = 0.002) and duration of mechanical ventilation (median 146.0 h, IQR 76.5-888.0 h vs. median 27.0 h, IQR 11.0-75.0 h, p = 0.002) were revealed to be longer in the levosimendan group. Peritoneal dialysis occurred in eight patients (40%) in the levosimendan group and two patients (10%) in the non-levosimendan group (p = 0.028). No significant difference was revealed in all-cause mortality within 180 days, which occurred in two patients (10%) in the levosimendan group and one (5%) in the non-levosimendan group (p = 1.00). Conclusion: Levosimendan's unique pharmacological properties have strong potential for cardiac function recovery among pediatric patients with ALCAPA with impaired left ventricular function who have undergone surgical repair.However, any improvement from levosimendan on postoperative outcomes or mortality was not substantiated by this study and must be investigated further.
Frontiers in pediatrics 2018
BACKGROUND:Levosimendan has been shown to confer direct renoprotection in renal endotoxemic and ischemia-reperfusion injury and could increase renal blood flow in patients with low-cardiac-output heart failure. Results from clinical trials of levosimendan on acute kidney injury (AKI) following cardiac surgery are controversial.STUDY DESIGN:A random-effect meta-analysis was conducted based on evidence from PubMed, EMBASE, and Cochrane Library.SETTINGS & POPULATION:Adult patients undergoing cardiac surgery.SELECTION CRITERIA FOR STUDIES:Randomized controlled trials comparing the renal effect of levosimendan versus placebo or other inotropic drugs during cardiac surgery.INTERVENTION:Perioperative levosimendan continuous infusion at a rate of 0.1 to 0.2μg/kg/min following a loading dose (6-24μg/kg) for 24 hours or only 1 loading dose (24μg/kg) within 1 hour.OUTCOMES:AKI, need for renal replacement therapy, mechanical ventilation duration, intensive care unit stay during hospitalization, and postoperative mortality (in-hospital or within 30 days).RESULTS:13 trials with a total of 1,345 study patients were selected. Compared with controls, levosimendan reduced the incidence of postoperative AKI (40/460 vs 78/499; OR, 0.51; 95% CI, 0.34-0.76; P=0.001; I(2)=0.0%), renal replacement therapy (22/492 vs 49/491; OR, 0.43; 95% CI, 0.25-0.76; P=0.002; I(2)=0.0%), postoperative mortality (35/658 vs 94/657; OR, 0.41; 95% CI, 0.27-0.62; P<0.001; I(2)=0.0%), mechanical ventilation duration (in days; n=235; weighted mean difference, -0.34; 95% CI, -0.58 to -0.09; P=0.007], and intensive care unit stay (in days; n=500; weighted mean difference, -2.2; 95% CI, -4.21 to -0.13; P=0.04).LIMITATIONS:Different definitions for AKI among studies. Small sample size for some trials.CONCLUSIONS:Perioperative administration of levosimendan in patients undergoing cardiac surgery may reduce complications. Future trials are needed to determine the dose effect of levosimendan in improving outcomes, especially in patients with decreased baseline kidney function.
American journal of kidney diseases : the official journal of the National Kidney Foundation 2016
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.
The Journal of surgical research 2014
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.
Acta pharmacologica Sinica 2014
BACKGROUND:It has been proved that sevoflurane postconditioning (SpostC) could protect the heart against myocardial ischemia/reperfusion injury, however, there has been few research focused on the electrophysiological effects of SpostC. The objective of the study was to investigate the effects of SpostC on action potential duration (APD) and L-type calcium current (I(Ca, L)) in isolated cardiomyocytes.METHODS:Langendorff perfused SD rat hearts were randomly assigned to one of the time control (TC), ischemia/reperfusion (I/R, 25 minutes of ischemia followed by 30 minutes of reperfusion), and SpostC (postconditioned with 3% sevoflurane) groups. At the end of reperfusion, epicardial myocytes were dissociated enzymatically for patch clamp studies.RESULTS:Sevoflurane directly prolonged APD and decreased peak I(Ca, L) densities in epicardial myocytes of the TC group (P < 0.05). I/R injury shortened APD and decreased peak I(Ca, L) densities in epicardial myocytes of the I/R group (P < 0.05). SpostC prolonged APD and increased peak I(Ca, L) densities in epicardial myocytes exposed to I/R injury (P < 0.05). SpostC decreased intracellular reactive oxygen species (ROS) levels, reduced the incidence of ventricular tachycardia and ventricular fibrillation, and decreased reperfusion arrhythmia scores compared with the I/R group (all P < 0.05).CONCLUSIONS:SpostC attenuates APD shortening and I(Ca, L) suppression induced by I/R injury. The regulation of APD and I(Ca, L) by SpostC might be related with intracellular ROS modulation, which contributes to the alleviation of reperfusion ventricular arrhythmia.
Chinese medical journal 2012
Sevoflurane postconditioning has been proven to protect the hearts against ischemia/reperfusion injury, manifested mainly by improved cardiac function, reduced myocardial specific biomarker release, and decreased infarct size. This study is to observe the effects of sevoflurane postconditioning on reperfusion-induced ventricular arrhythmias and reactive oxygen species generation in Langendorff perfused rat hearts. Compared with the unprotected hearts subjected to 25 min of global ischemia followed by 30 min of reperfusion, exposure of 3% sevoflurane during the first 15 min of reperfusion significantly improved cardiac function, reduced cardiac troponin I release, decreased infarct size and attenuated reperfusion-induced ventricular arrhythmia. Further analysis on arrhythmia during the 30 min of reperfusion showed that, sevoflurane postconditioning decreased both the duration and incidence of ventricular tachycardia and ventricular fibrillation. In the meantime, intracellular malondialdehyde and reactive oxygen species levels were also reduced. These above results demonstrate that sevoflurane postconditioning protects the hearts against ischemia/reperfusion injury and attenuates reperfusion-induced arrhythmia, which may be associated with the regulation of lipid peroxidation and reactive oxygen species generation.
Molecular biology reports 2012
