Liver transplantation for pediatric patients with congenital heart disease: A single-center study in mainland China.

BACKGROUND: Liver transplantation (LT) is a serious cardiovascular stressor for patients with end-stage liver disease (ESLD). Data on the effects of cardiovascular diseases on pediatric LT is limited. No study on LT for pediatric patients with ESLD combined with congenital heart disease (CHD) has been reported from mainland China. METHODS: A total of 1005 patients were included in this study. The Kaplan-Meier method with log-rank testing was used to evaluate survival outcomes between groups. Univariable and multivariable Cox regression models were used to determine the risk factors for patient and graft survival. RESULTS: The most common indication for LT was biliary atresia (BA 90.3%). The prevalence of CHD was 3.8% (38). 42 CHD were found in 38 patients. The incidence of death and graft loss was more common in the CHD group than in the no-CHD group (13.2% vs. 5.0%, p = .045 and 15.8% vs. 6.2%, p = .019, respectively). The 5-year patient survival and graft survival in the CHD group versus the no-CHD group was 86.8% versus 94.7% (log-rank p = .022) and 84.2% versus 93.5% (log-rank p = .015), respectively. No significant differences were observed in re-transplantation, hepatic artery thrombosis (HAT), and portal vein thrombosis (PVT). After adjusting for age, BMI, etiology of LT, and other confounding factors, we can still find that the presence of CHD was associated with patient and graft survival after LT. CONCLUSION: The presence of CHD was associated with higher mortality and lower graft survival after LT. If possible, the cardiac defects should be addressed prior to LT.

Association between oxidative balance score and resistant hypertension and arterial stiffness among US adults: A population-based study.

BACKGROUND AND AIMS: Prior studies have established the correlation between oxidative balance score (OBS) and hypertension (HTN). While the association between OBS and resistant hypertension (RHT) as well as arterial stiffness among individuals with hypertension remains undisclosed. METHODS AND RESULTS: In this study, total of 15,910 adults diagnosed with hypertension were enrolled from NHANES 2001-2018. OBS was calculated and categorized into quartiles. Weighted regression model, stratified analyses and restricted cubic spline (RCS) were employed to evaluate the association between OBS and RHT, major adverse cardiovascular events (MACEs) and arterial stiffness in individuals with hypertension. Among enrolled participants, high OBS quartiles consistently demonstrated a negative association with resistant hypertension across all models (all p < 0.05), indicating robust stability. Compared with the lowest OBS quartile, the risk of resistant hypertension in the highest OBS quartile was decreased by 30.8% (95%CI 0.471-0.995, p = 0.049). After dividing OBS into dietary OBS and lifestyle OBS, a significant inverse association with lifestyle OBS and RHT was observed. With regard to MACEs, the inverse association was also found in participants with high OBS. Besides, the potential relation between OBS and arterial stiffness was explored and we found OBS was significantly associated with decreased arterial stiffness (ß for ePWV, -0.014; 95%CI -0.026 to -0.001; p = 0.032). RCS analysis confirmed a nonlinear association between OBS and RHT, MACEs, cardiovascular death and nonfatal MI among participants with hypertension. CONCLUSION: Elevated OBS was negatively associated with the risk of RHT and arterial stiffness among US adults with hypertension.

Role of CCRL2 in the Pathogenesis of Experimental Autoimmune Myocarditis via P21-Activated Kinase 1/NOD-Like Receptor Protein 3 Pathway.

Myocarditis, a severe inflammatory disease, is becoming a worldwide public health concern. This study aims to elucidate the effect of Chemokine (C C motif) receptor-like 2 (CCRL2) in experimental autoimmune myocarditis (EAM) occurrence and its potential regulatory mechanisms.EAM was simulated in a mouse model injected with α-myosin-heavy chain. The changes on EAM were assessed through histological staining of heart tissues, including measuring cardiac troponin I (cTnI), proinflammatory cytokines, transferase-mediated dUTP nick end labeling (TUNEL) assay, and cardiac function. Then, the heart tissues from the EAM mouse model and control groups were analyzed through transcriptome sequencing to identify the differential expressed genes (DEGs) and hub genes related to pyroptosis. Downregulation of CCRL2 further verified the function of CCRL2 on EAM and p21-activated kinase 1/NOD-like receptor protein 3 (PAK/NLRP3) signaling pathways in vivo.The EAM model was constructed successfully, with the heart weight/body weight ratio, serum level of cTnI, and concentrations of proinflammatory cytokines elevation. Moreover, cell apoptosis was also significantly increased. Transcriptome sequencing revealed 696 and 120 upregulated and downregulated DEGs, respectively. After functional enrichment, CCRL2 was selected as a potential target. Then, we verified that CCRL2 knockdown improved cardiac function, alleviated EAM occurrence, and reduced PAK/NLRP3 protein expression.CCRL2 may act as a novel potential treatment target in EAM by regulating the PAK1/NLRP3 pathway.

Influencing factors and prognostic value of left ventricular systolic dysfunction in patients with complete occlusion of the left anterior descending artery reperfused by primary percutaneous coronary intervention.

BACKGROUND: The aim of this study was to perform a retrospective analysis of patients with acute anterior wall ST-segment elevation myocardial infarction (AAW-STEMI) whose left anterior descending (LAD) artery was completely occluded and reperfused by primary percutaneous coronary intervention (PPCI) and to determine the influencing factors and prognostic value of left ventricular systolic dysfunction (LVSD) in the acute phase of acute myocardial infarction (AMI). METHODS: A total of 304 patients with AAW-STEMI were selected. The selected patients were divided into two groups: the preserved left ventricular ejection fraction (pLVEF) group (LVEF ≥ 50%, n = 185) and the reduced left ventricular ejection fraction (rLVEF) group (LVEF < 50%, n = 119). The influencing factors of LVSD and their predictive value for LVSD were analyzed. Patients were followed up by examining outpatient records and via telephone. The predictive value of LVSD for the cardiovascular mortality of patients with AAW-STEMI was analyzed. RESULTS: Age, heart rate (HR) at admission, number of ST-segment elevation leads (STELs), peak creatine kinase (CK) and symptom to wire-crossing (STW) time were independent risk factors for LVSD (P < 0.05). The receiver operating characteristic (ROC) analysis showed that the peak CK had the strongest predictive value for LVSD, with an area under the curve (AUC) of 0.742 (CI, 0.687 to 0.797) as the outcome. At a median follow-up of 47 months (interquartile range, 27 to 64 months), the Kaplan‒Meier survival curves up to 6-year follow-up revealed a total of 8 patients succumbed to cardiovascular disease, with 7 (6.54%) in the rLVEF group and 1 (0.56%) in the pLVEF group, respectively (hazard ratio: 12.11, [P = 0.02]). Univariate and multivariate Cox proportional hazards regression analysis demonstrated that rLVEF was an independent risk predictor of cardiovascular death in patients with AAW-STEMI discharged after PPCI (P < 0.01). CONCLUSIONS: Age, HR at admission, number of STELs, peak CK, and STW time may be used to identify patients with a high risk of heart failure (HF) in a timely manner and initiate early standard therapy for incident LVSD in the acute phase of AAW-STEMI reperfused by PPCI. A trend toward increased cardiovascular mortality at follow-up was significantly linked to LVSD.

Superior mesenteric artery embolism after radiofrequency ablation in regularly anticoagulated patients with paroxysmal atrial fibrillation: a case report.

BACKGROUND: Superior mesenteric artery embolism (SMAE) is a rare cause of acute abdomen, and the fatality rate is extremely high if it is not diagnosed and treated in time. Due to the lack of knowledge and experience of nonspecialist physicians, it is easy to misdiagnose. Radiofrequency ablation (RFA) has become the first-line treatment strategy for atrial fibrillation (AF). Thromboembolic events are some of the major complications after RFA, whereas SMAE is rarely reported. CASE PRESENTATION: A 70 year-old woman with paroxysmal AF who regularly took anticoagulant drugs for 3 months experienced abdominal pain after RFA. At the outset, she was misdiagnosed as mechanical intestinal obstruction. When the patient presented with blood in the stool, abdominal enhancement computed tomography was conducted and showed a small bowel perforation. Immediate laparotomy was performed, and the final diagnosis was SMAE. CONCLUSION: It is suggested that for unexplained abdominal pain after RFA of AF, the possibility of SMAE should be considered, and a targeted examination should be carried out in time to confirm the diagnosis and give appropriate treatment.

Colchicine-Containing Nanoparticles Attenuates Acute Myocardial Infarction Injury by Inhibiting Inflammation.

PURPOSE: Anti-inflammatory therapy is important for reducing myocardial injury after acute myocardial infarction (MI). New anti-inflammatory drugs and their mechanism are necessary to be explored to improve clinical efficacy. We aimed to improve the efficacy of colchicine on attenuating MI injury by nano-drug delivery systems and to investigate the mechanism of anti-inflammatory. METHODS: A colchicine-containing delivery system based on calcium carbonate nanoparticles (ColCaNPs) was synthesized. The protection against MI by ColCaNPs was evaluated using an in vivo rat model established by ligating the left anterior descending coronary artery. Macrophage polarization and the levels of inflammatory cytokines were determined using immunohistochemistry, Western blot, and ELISA analysis. RESULTS: ColCaNP treatment showed about a 45% reduction in myocardial infarct size and attenuating myocardial fibrosis compared with groups without drug intervention after MI. Furthermore, ColCaNPs significantly decreased the levels of CRP, TNF-α, and IL-1ß in serum and the expression of proinflammatory cytokine in myocardial tissues after MI (p < 0.05). We also found that ColCaNPs notably restrained pyroptosis and inhibited inflammatory response by modulating on M1/M2 macrophage polarization and suppressing TLR4/NFκB/NLRP3 signal pathway. CONCLUSION: Colchicine-containing nanoparticles can protect against MI injury in a clinically relevant rat model by reducing inflammation. In addition, calcium carbonate nanoparticles can increase the cardioprotective effects of colchicine.

Enhanced stent visualization system for percutaneous coronary intervention in patients with chronic kidney disease: effects on contrast media volume and radiation exposure.

OBJECTIVE: We aimed to assess the impact of using enhanced stent visualization (ESV) systems on contrast media volume and radiation dose in percutaneous coronary intervention (PCI), especially for patients with chronic kidney disease (CKD). BACKGROUND: Coronary heart disease (CHD) is associated with chronic kidney disease (CKD), as they share a similar pathological pathway. In addition, the iodinated contrast media used for angiography is a risk factor for contrast-associated acute kidney injury (CA-AKI), which could aggravate the progression of CKD. We hypothesized that ESV systems have the potential to reduce the use of contrast media as well as the radiation dose; however, few studies have reported the impact on contrast media with the use of ESV systems. METHODS: We retrospectively collected 124 patients with acute coronary syndrome who underwent PCI from May 2020 to July 2021. The patients were divided into the ESV-guided group (n = 64) and angiography-guided group (n = 60). Procedural parameters, including contrast media volume, radiation exposure (in Air Kerma-AK and Dose Area Product-DAP), number of cines, cine frames, fluoroscopy and procedure time, were recorded and analysed. RESULTS: The groups were comparable regarding the patient characteristics. There was a significant reduction in contrast media volume (174.7 ± 29.6 ml vs.132.6 ± 22.3 ml, p = 0.0001), radiation exposure (776 (499 - 1200) mGy vs. 1065 (791 - 1603) mGy, p = 0.002 in AK; 43 (37 - 73) Gycm2 vs. 80 (64 - 133) Gycm2, p = 0.030 in DAP) and procedure time (53.06 ± 21.20 min vs. 72.00 ± 30.55 min, p = 0.01) with the use of ESV systems. Similar results were observed in the subgroup analysis for the patients with CKD. CONCLUSION: This study suggested that the use of ESV is associated with reduced contrast media usage, radiation dose and procedure time during PCI. The same results were observed in a subgroup analysis in patients with CKD, and this shows that ESV-guided PCI has the potential to reduce renal impairment and mitigate the progression of CKD for those CHD patients with CKD.

Efficacy and safety of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis.

Objective: To evaluate the efficacy and safety of soluble guanylate cyclase (sGC) stimulators in patients with heart failure (HF). Methods: A systematic literature search from several electronic databases (Web of Science, PubMed, Embase, Medline) was performed up until March 2021. Eligible studies included randomized controlled trials (RCTs) that compared sGC stimulators treatment with placebo. Data extracted from eligible RCTs were pooled using relative risk (RR) and weight mean difference (WMD) on random effect model or fixed effect model. Results: A total of eight RCTs involving 7225 patients met the inclusion criteria. For the efficacy endpoint, sGC stimulators significantly reduced HF-related hospitalization or cardiovascular (CV) death (RR = 0.92, 95%CI: 0.86-0.99; P = 0.03), but no relationship was found for 6-minute walking distance (6MWD) (SMD = 0.04, 95%CI: -0.09-0.17; P = 0.55). In addition, compared to control group, the change of NT-proBNP was statistically decreased in the riociguat group (SMD = -0.78, 95%CI: -1.09--0.47; P < 0.00), yet not in vericiguat group (SMD = 0.05, 95%CI: -0.19-0.28; P = 0.70). For the safety endpoint, there was no significant difference in all-cause mortality (RR = 0.98 95%CI: 0.88-1.09; P = 0.69) and serious adverse events (RR = 0.95, 95%CI: 0.892-1.02; P = 0.16) between SGC stimulants group and control group. Conclusion: The oral therapy with sGC stimulators including vericiguat and riociguat decreases the incidence of HF-related hospitalization or CV death with good tolerability and safety. The study did not support improvement in many parameters including 6MWD and NT-proBNP in HF patients.

Effect of Renal Denervation on Cardiac Function and Inflammatory Factors in Heart Failure After Myocardial Infarction.

Heart failure (HF) affects around 100 million people and is a staggering burden for health care system worldwide. Rapid and sustained activation of inflammatory response is an important feature of HF after myocardial infarction. Sympathetic overactivation is also an important factor in the occurrence and progression of HF. The beneficial effect of renal denervation (RDN) has been demonstrated in HF. In the current study, we hypothesized that RDN improves cardiac function in HF canine models due to acute myocardial infarction (AMI) and reduced inflammation might be involved. Twenty-four beagles were randomized into the control (n = 8), HF (n = 8), and HF + RDN group (n = 8). The HF model after AMI was established by embolization the anterior descending distal artery with anhydrous ethanol in the HF and HF + RDN group. Bilateral renal artery ablation was performed in the HF + RDN group. Cardiac function, serum creatine kinase, creatine kinase-MB and NT-Pro BNP level, and expression of inflammation-related proteins in myocardial were examined. Because the paraventricular nucleus of the hypothalamus might be involved in inflammation-induced central neural excitation in HF and plays an important role in regulating extracellular fluid volume and sympathetic activity, expression of inflammation-related proteins in hypothalamus was also examined. AMI and post-AMI HF model was created successfully. Compared with the HF group, dogs in the HF + RDN group showed better cardiac function 4 weeks after AMI: lower left ventricular end-diastolic pressure, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension and higher LEVF and left ventricular systolic pressure (P < 0.05 for all) were observed in the HF + RDN group. In addition, dogs in the HF + RDN group had slightly less ventricular fibrosis. Interestingly, RDN had lower expression of inflammation-related proteins including interleukin-6, tumor necrosis factors-α, nuclear factor κB, and monocyte chemotactic protein 1 (P < 0.05 for all) in both myocardial tissue and hypothalamus. RDN can improve cardiac function in dogs with HF after myocardial infarction. Our results suggested that RDN might affect cytokine-induced central neural excitation in HF and later affect sympathetic activity. Our results suggested a potential beneficial mechanism of RDN independent of mechanism involving renal afferent and efferent sympathetic nerves.

The relationship between serum uric acid and cognitive function in patients with chronic heart failure.

BACKGROUND: Evidence has shown that serum uric acid (UA) is associated with cognitive function, but this finding remains debatable. Serum UA is commonly elevated in patients with chronic heart failure (CHF), especially in men. However, the relationship between serum UA and cognitive function in CHF populations and stratified by sex are unclear. We aimed to examine whether serum UA was independently associated with cognitive function in CHF populations after controlling for demographic, medical and psychological variables and whether there was a sex difference in the association between serum UA and cognitive function among male and female CHF patients. METHODS: One hundred ninety-two hospitalized patients with CHF underwent an assessment of cognitive function using the Montreal Cognitive Assessment (MoCA) and the determination of serum UA. Hyperuricemia was defined as serum UA ≥7 mg/dl in men and ≥ 6 mg/dl in women. Multiple linear hierarchical regression analyses were conducted to examine the independent association between serum UA and cognitive function in CHF populations and stratified by sex. RESULTS: The mean serum UA concentration of participants was 7.3 ± 2.6 mg/dL. The prevalence of hyperuricemia was 54.7% (105 of 192) in CHF patients, 52.9% (64 of 121) in men, and 57.7% (41 of 71) in women. In the total sample, higher serum UA was associated with poorer cognitive function independent of demographic, medical and psychological variables (ß = - 0.130, ΔR2 = 0.014, p = 0.015). In sex-stratified groups, elevated serum UA was independently associated with worse cognitive function in men (ß = - 0.247, ΔR2 = 0.049, p = 0.001) but not in women (ß = - 0.005, ΔR2 = 0.000, p = 0.955). CONCLUSIONS: Higher serum UA is independently associated with poorer cognitive function in CHF populations after adjusting for confounding variables. Furthermore, elevated serum UA is independently related to worse performance on cognitive function in men but not in women. More longitudinal studies are needed to examine the association between serum UA and cognitive function in CHF populations and stratified by sex.

Galectin-3 inhibition attenuates doxorubicin-induced cardiac dysfunction by upregulating the expression of peroxiredoxin-4.

Doxorubicin (DOX) is a highly efficient chemotherapeutic drug limited by its cardiotoxicity. Galectin-3 (Gal-3) overexpression is associated with several cardiovascular diseases. In this study, the in vivo models of DOX-treated rats and the in vitro model of DOX-treated H9C2 cells were used. DOX induced cardiac injury and dysfunction accompanied with the upregulation of Gal-3 at the end of the experiment, while inhibition of Gal-3 with modified citrus pectin (MCP) exhibited a dramatic improvement in cardiac function of the DOX-treated rats, as manifested by increased left ventricular systolic pressure and ±dp/dtmax and decreased left ventricular end-diastolic pressure. The plasma levels of myocardial injury markers such as lactate dehydrogenase, creatine kinase, creatine kinase-MB, and cardiac troponin I were decreased after MCP treatment. In parallel, MCP attenuated myocardial tissue markers of oxidative stress such as hydrogen peroxide and malondialdehyde restored the activities of superoxide dismutase, catalase, and glutathione peroxidase and upregulated antioxidant peroxiredoxin-4 (Prx-4). To further verify the role of Prx-4, it was downregulated by siRNA-mediated knockdown in H9C2 cells. MCP could not reverse DOX-induced oxidative stress in Prx-4-knock-down cells. In conclusion, Gal-3 mediated DOX-induced cardiotoxicity and Gal-3 inhibition attenuated DOX-induced cardiac dysfunction by upregulating the expression of Prx-4 to reduce myocardial oxidative stress.

Inhibition of HES-1 might play a protective role in endothelial cells under cholesterol stimulation via PI3K/AKT signaling pathway.

The occurrence of atherosclerotic cardiovascular disease (ASCVD) was closely related to low-density lipoprotein (LDL) cholesterol. HES-1 is critical for maintains of stem cells, quiescent cells or cancer cells, and contributes to drug resistance and metastasis of tumor cells. In this study, we established a cell model of HES-1 inhibition and overexpression in Ea.hy 926 cells, and firstly detected the proliferation rete of Ea.hy 926 cells under cholesterol stimulation using MTT assay, and apoptosis of Ea.hy 926 cells were detected using flow cytometry. Expression of HES-1, apoptosis related proteins and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway were detected using Western blotting analysis. The expression of apoptotis related genes were detected using polymerase chain reaction (PCR) method. The concentration of angiogenesis cytokines was detected using enzyme-linked immunosorbent assay (ELISA) method. We found that proliferation of Ea.hy 926 cells was inhibited after stimulation of cholesterol, inhibition of HES-1 expression would reduce this effect. We also found that expression of apoptosis related molecules was increased and expressions of angiogenesis factors were decreased after cholesterol treatment. Besides, we revealed that these effects were mediated via PI3K/AKT signaling pathway, and HES-1 inhibition could increase the activity of this signaling pathway.

MiR-495 regulates macrophage M1/M2 polarization and insulin resistance in high-fat diet-fed mice via targeting FTO.

MicroRNA 495 (miR-495) has been discovered to be involved in the metabolism and immune response in human body. The purpose of this study was to investigate the effect of miR-495 on macrophage M1/M2 polarization and insulin resistance in type 2 diabetes (T2D). A T2D mouse model was established by feeding C57BL/6 mice with a high-fat diet (HFD). The expressions of M1/M2 polarization markers and miR-495 in peritoneal macrophages were determined by qRT-PCR or Western blot. Mouse insulin tolerance test (ITT) and glucose tolerance test (GTT) were performed, and the targeted binding effect between miR-495, fat mass, and obesity-associated gene (FTO) was verified by double luciferase gene reporter assay. The body weight, blood glucose content, and miR-495 expression in macrophages of the HFD group were remarkably higher than those of the normal diet (ND) group. Besides, miR-495 induced the transformation of macrophages into M1-type pro-inflammatory macrophages and enhanced the insulin resistance of T2D mice. More importantly, FTO was proved to be a direct target gene of miR-495 and silencing FTO could induce the transformation of macrophages into M1-type pro-inflammatory macrophages. These results demonstrated that miR-495 could promote the transformation of macrophages into M1-type pro-inflammatory macrophages by inhibiting the expression of its target gene FTO, and aggravate the insulin resistance and adipose tissue inflammation in T2D mice, which provided a certain theoretical basis for the targeted treatment of T2D.

LATS2 promotes cardiomyocyte H9C2 cells apoptosis via the Prx3-Mfn2-mitophagy pathways.

Context: The pathogenesis of cardiomyocyte death is closely associated with mitochondrial homeostasis via poorly understood mechanisms.Objective: The aim of our study is to explore the contribution of large tumor suppressor kinase 2 (LATS2) to the apoptosis of cardiomyocyte H9C2 cells.Materials and Methods: Adenovirus-mediated LATS2 overexpression was carried out in H9C2 cells. The cell viability and apoptosis rate were measured via an MTT assay, TUNEL staining, western blotting, an ELISA, and an LDH release assay. Mitophagy was quantified using immunofluorescence and western blotting.Results: The overexpression of LATS2 in H9C2 cells drastically promoted cell death. Molecular investigations showed that LATS2 overexpression was associated with mitochondrial injury, as evidenced by increased mitochondrial ROS production, reduced antioxidant factor levels, increased cyt-c liberation into the nucleus and activated mitochondrial caspase-9-dependent apoptotic pathway activity. Furthermore, our results demonstrated that LATS2-mediated mitochondrial malfunction by repressing mitophagy and that the reactivation of mitophagy could sustain mitochondrial integrity and homeostasis in response to LATS2 overexpression. Furthermore, we found that LATS2 inhibited mitophagy by inactivating the Prx3-Mfn2 axis. The reactivation of Prx3-Mfn2 pathways abrogated the LATS2-mediated inhibition of mitochondrial apoptosis in H9C2 cells.Conclusions: The overexpression of LATS2 induces mitochondrial stress by repressing protective mitophagy in a manner dependent on Prx3-Mfn2 pathways, thus reducing the survival of H9C2 cells.

Early Renal-Protective Effects of Remote Ischemic Preconditioning in Elderly Patients with Non-ST-Elevation Myocardial Infarction (NSTEMI).

BACKGROUND With the wide clinical application of angiography, contrast-enhanced nephropathy (CIN) has become the third-leading cause of acute kidney injury (AKI). Remote ischemic preconditioning (RIPC) is a non-fatal ischemia-reperfusion injury that can provide protection against lethal ischemia-reperfusion. This study aimed to assess the effect of RIPC on CIN in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). MATERIAL AND METHODS Patients were randomly divided into 2 groups with 119 patients in each group treated with interventional therapy. Patients in the RIPC group received distal ischemic preconditioning 2 h before contrast exposure, while patients in the control group received a sham RIPC procedure. Incidence of CIN was the primary outcome. Changes in creatinine, NGAL, and KIM-1 after contrast administration were secondary outcomes. RESULTS CIN occurred in a total of 27 (12.3%) patients, including 12 (10.1%) in the RIPC group and 15 (15.1%) in the control group (P=0.329). RIPC treatment significantly reduced the levels of NGAL (P=0.024) and KIM-1 (P=0.007) at 12 h after contrast administration, suggesting RIPC treatment reduces sub-clinical renal damage. Subgroup analysis revealed that significant reduction of KIM-1 and NGAL by RIPC, mainly occurring in patients with a Mehran risk score of 6-10. CONCLUSIONS Although RIPC did not significantly reduce CIN incidence in elderly patients with NSTEMI, the application of more sensitive biomarkers - NGAL and KIM-1 - indicated a reduction of sub-clinical renal damage by RIPC, especially in the early stage of injury. As a simple and well-tolerated method, RIPC may be a potentially feasible option to prevent CIN.

Efficacy of alprostadil in preventing contrast-induced nephropathy in patients undergoing percutaneous coronary intervention: A multicenter prospective randomized controlled trial.

BACKGROUND: The role of alprostadil on the prevention of contrast-induced nephropathy (CIN) still remains controversial. The purpose of this study was to examine the effects of short-term alprostadil on the incidence of CIN in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: A total of 480 patients with coronary heart disease undergoing PCI were enrolled in our study and randomly assigned to two groups. The control group (n = 240) was given only hydration therapy and the alprostadil group (n = 240) received intravenous administration of 20 ug/day (diluted with 100 ml normal saline) from 0.5∼1 hr before to 3 days after operation on the basis of hydration. The primary endpoint of the study was the incidence of CIN, which was defined as an increase in SCr concentration ≥ 44.2 umol/l or ≥25% above baseline within 48 hr∼72 hr after exposure of contrast media. RESULTS: The incidence of CIN was significantly lower in the alprostadil group than that in the control group (6.25% vs 11.67%, P = 0.038). Multivariate logistic regression analysis showed that alprostadil was the protective factor of CIN (OR = 0.699, 95% CI 0.542-0.902, P = 0.006). The benefits against CIN were consistent in prespecified high-risk patients with diabetes mellitus (P = 0.003). In addition, we also found that hs-CRP and blood homocysteine values after PCI were significantly lower in the alprostadil group than those in the control group. CONCLUSION: Prophylactic administration of alprostadil may prevent against CIN in coronary heart disease patients undergoing elective PCI, particularly in high-risk patients with diabetes mellitus.

Renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction.

BACKGROUND: Myocardial apoptosis is important in the pathogenesis and progression of myocardial infarction-induced heart failure (MI-HF). Renal sympathetic denervation (RDN) has become a promising therapeutic strategy for the treatment of HF. Previous studies have shown that RDN could improve heart function Yao et al. (Exp Ther Med 14:4104-4110, 2017). However, whether and how RDN regulates myocardial apoptosis in MI-HF is unclear. This study sought to evaluate the effects of RDN on cardiac function and apoptosis-related gene expression in MI-HF dogs. METHODS: Eighteen healthy mongrel dogs were randomly divided into control group(n = 6), model group(n = 6) and treatment group(n = 6). MI-HF was established in model group and treatment group by anhydrous alcohol embolization, after heart failure dogs in the treatment group and model group proceeded bilateral renal artery ablation and bilateral renal arteriography, respectively. The cardiac function parameters were evaluated by echocardiographic; the serum NT-BNP level was detected by ELISA; the degree of myocardial fibrosis was observed through masson staining; the expression of MMP-2, MMP-9 in the cardiac were got by immunohistochemistry. TUNEL method was used to observe cardiomyocyte apoptotsis and calculate the apoptosis index (AI). Relative expression of Bcl-2 and Bax, Caspase3 and GRP78 were detected using RT-PCR and Western Blot. Renal artery H&E staining and serum creatinine were conducted to access the efficacy and safety of RDN. RESULTS: Four weeks after RDN, the LVEDD, LVESD and LVEDP decreased, and the LVEF and LVSP increased in the treatment group compared with those in the control group (all P < 0.05). Moreover, NT-BNP, an indicator of cardiac function was decreased. Additionally, MMP-2 and MMP-9 levels in the myocardium decreased significantly in the treatment group. Furthermore, the levels of Bax, and caspase 3 decreased, while the level of Bcl-2 increased. Thus, myocardial apoptosis was attenuated in RDN treated dogs. We also found that the level of GRP78 which is activated in response to endoplasmic reticulum (ER) stress, was decreased. However, serum creatinine levels were not significantly different between the RND-treated dogs and the control dogs. CONCLUSION: Cardiac function was improved by RDN treatment through regulating apoptosis and ER stress in cardiomyocytes in dogs after MI.

Effects of renal denervation on cardiac oxidative stress and local activity of the sympathetic nervous system and renin-angiotensin system in acute myocardial infracted dogs.

BACKGROUND: This study sought to evaluate the therapeutic effects of renal denervation (RDN) on acute myocardial infarction (MI) in canines and explore its possible mechanisms of action. METHODS: Eighteen healthy mongrel dogs were randomly assigned to either the control group, the MI group or the MI + RDN group. To assess cardiac function, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and fraction shortening (FS) were recorded. Additionally, haemodynamic parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate (HR) were measured. Cardiac oxidative stress levels were evaluated based on the expression of p47phox mRNA, malondialdehyde (MDA), anti-superoxide anion free radical (ASAFR) and activity of superoxide dismutase (SOD). To measure the local activity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS), the levels of tyrosine hydroxylase (TH), angiotensin II (AngII), angiotensin-converting enzyme 2 (ACE2), angiotensin (1-7) [Ang(1-7)] and Mas receptor (MasR) in myocardial tissues were recorded. The expression of TH in renal tissue and serum creatinine were used to assess the effectiveness of the RDN procedure and renal function, respectively. RESULTS: We found that MI deteriorated heart function and activated cardiac oxidative stress and the local neurohumoral system, while RDN partially reversed these changes. Compared with the control group, parameters including LVEDD, LVESD, LVEDP and the levels of ASAFR, MDA, p47phox,ACE2, Ang(1-7), MasR, AngII and TH-positive nerves were increased (all P < 0.05) in myocardial infracted dogs; meanwhile, LVEF, FS, LVSP and SOD expression were decreased (all P < 0.05). However, after RDN therapy, these changes were significantly improved (P < 0.05), except that there were no significant differences observed in FS or LVSP between the two groups (P = 0.092 and 0.931, respectively). Importantly, the expression of TH, AngII and Ang(1-7) was positively correlated with MDA and negatively correlated with SOD. Between-group comparisons demonstrated no differences in serum creatinine (P = 0.706). CONCLUSIONS: RDN attenuated cardiac remodelling and improved heart function by decreasing the level of cardiac oxidative stress and the local activity of the SNS and RAS in cardiac tissues. Additionally, the safety of the RDN procedure was established, as no significant decrease in LVSP or rise in serum creatinine was observed in our study.