Transcatheter tricuspid valve-in-valve implantation for degenerated surgical bioprosthesis.

BACKGROUND: Isolated redo surgery for degenerated tricuspid bioprosthesis is of very high risk. We aimed to evaluate the safety and efficacy of transcatheter valve-in-valve (TVIV) implantation using a novel balloon expandable Renato valve. METHODS: A prospective multicenter study was conducted to enroll patients with degenerated tricuspid bioprostheses. A total of 12 patients underwent TVIV implantation using the Renato valve system via transfemoral, transjugular, or transatrial approaches at three institutions from May 2021 to October 2021. All-cause mortality and hemodynamic performance were evaluated up to 6 months after procedure. RESULTS: The median age was 68.2 years, and 75.0% were female. Six patients had a history of rheumatic left-sided valve surgery and late tricuspid valve replacement. The median preoperative Society of Thoracic Surgeons score was 9.9%. The procedures were successful in all cases. Tricuspid regurgitation and paravalvular leak were none or mild in all patients. The median transvalvular gradient decreased from 7.8 mmHg preoperatively to 4.5 mmHg at 6 months after TVIV, respectively. No death occurred and all patients recovered to New York Heart Association functional class I or II during a 6-month follow-up. CONCLUSIONS: TVIV implantation with the Renato valve was a safe and effective treatment for degenerated bioprostheses in high-risk patients.

microRNA-665 silencing improves cardiac function in rats with heart failure through activation of the cAMP signaling pathway.

Heart failure (HF) is a disease with high mortality and morbidity rate. Previous studies have shown that microRNAs (miRNAs) may be implicated in the pathogenesis of HF, potentially being able to improve the cardiac function in an HF rat model. The present study was designed to define the role of miR-665 in the cardiac function of the HF rats. Following the establishm;ent of the rat models of HF, the functional role miR-665 in HF was determined using an ectopic expression and knockdown experiments. The cardiac function was evaluated with the determination of ventricular mass index and hemodynamic parameters. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining was performed, with the apoptosis of cardiac cells detected in the process. The expression of miR-665, glucagon-like peptide 1 receptor (GLP1R), cyclic adenosine monophosphate (cAMP) signaling pathway-related, and apoptosis-related genes was examined. Enzyme-linked immunosorbent assay was conducted to determine the levels of inflammation-related genes. Initially, the upregulation of miR-665, downregulation of GLP1R, and inactivation of cAMP signaling pathway were observed in HF rats. GLP1R was a target of miR-665. Forced expression of miR-665 promoted cell apoptosis and inhibited GLP1R and the cAMP signaling pathway. In addition, miR-665 overexpression has been known to impair cardiac function, promote inflammatory response while elevating malondialdehyde and superoxide dismutase levels, and decreasing mitochondrial respiratory chain enzyme activities. Furthermore, we also observed that the effects of miR-665 inhibition had been reversed when the cAMP signaling pathway was also inhibited. This study demonstrates that miR-665 inhibition can stabilize the cardiac function of HF rats via the cAMP signaling pathway via upregulation of the GLP1R.

DUSP14 knockout accelerates cardiac ischemia reperfusion (IR) injury through activating NF-κB and MAPKs signaling pathways modulated by ROS generation.

Inflammation and oxidative stress are significantly involved in the progression of a variety of diseases, including myocardial ischemia/reperfusion (IR). In the present study, we hypothesized a protective role of dual-specificity phosphatase 14 (DUSP14) in myocardial IR, as well as the underlying molecular mechanism. The results indicated that DUSP14 was down-regulated following cardiac IR injury. Subsequently, the wild type (WT) and DUSP14-knockout (KO) mice were included to further reveal the potential role of DUSP14 in cardiac IR injury progression. DUSP14-KO mice exhibited increased infarction area and elevated apoptosis, as evidenced by the increased TUNEL-positive cells in ischemia heart following reperfusion compared to WT mice. Further, DUSP14-KO significantly aggregated cardiac dysfunction of mice after IR injury. Cardiac IR injury to DUSP14-KO mice led to markedly increased expression of pro-inflammatory cytokines and activated nuclear factor-κB (NF-κB) pathway in the heart in comparison to WT mice. Meanwhile, mitogen-activated protein kinases (MAPKs), including p38, ERK1/2 and JNK, were significantly activated by DUSO14-KO in mice after IR injury. Compared to WT mice, DUSP14-KO mice showed markedly increased oxidative stress markers in cardiac tissues, including malondialdehyde (MDA), NADPH oxidase-4 (NOX4) and p47, while decreased activities or expressions of anti-oxidants, such as glutathione (GSH), glutathione peroxidase (GPx), glutathion reductases (GR), superoxide dismutase (SOD) and hemeoxygenase-1 (HO-1). DUSP14-knockdown (KD) in primary cardiomyocytes using its specific siRNA sequence elevated hypoxia and reoxygenation (HR)-induced activation of NF-κB and MAPKs signaling pathways, and reactive oxygen species (ROS) generation. Intriguingly, pre-treatment of ROS scavenger, N-acetylcysteine (NAC), markedly abolished DUSP14-KD-augmented NF-κB and MAPKs activation in HR-stimulated primary cardiomyocytes. Together, the results above indicated that DUSP14 might be served as a positive regulator to attenuate cardiac IR injury. Suppressing DUSP14 exacerbated cardiac injury through activating NF-κB and MAPKs signaling pathways regulated by ROS production. Thus, DUSP14 could be a valuable target for developing treatments for myocardial IR injury.

Ferroptosis Exists in Ischemia Reperfusion Injury after Cardiac Surgery with Cardiopulmonary Bypass.

Ischemia-reperfusion (IR) injury commonly arises during cardiac surgery involving Cardiopulmonary Bypass (CPB), and it has relationship with ferroptosis in mice. However, the exact role of ferroptosis in the human cardiac damage caused by cardiac surgery remains unclear. Basic patient data and perioperative period information were collected, and clinic indicators related to cardiac function were detected to assess the extent of cardiac injury. Cardiac tissue samples were collected to determine histopathological changes, ultrastructure of mitochondrial and hallmarks of ferroptosis. 25 patients were involved in this study. In the present study, we observed a significant increase in the clinical indicator hs-cTnT, with levels rising more than 1393 ± 242 folds (P < 0.0001) following the cardiac surgery. Masson staining revealed a notable increase in fibrosis levels by 2.282 ± 0.259% (P = 0.0009). Furthermore, there was a significant elevation in lipid peroxidation, as evidenced by a 61.42 ± 17.33% increase in MDA (P = 0.0006). Additionally, we observed notable swelling, decreased mitochondrial crista, and even fragmented mitochondria. Notably, changes in the marker gene of ferroptosis were observed, with PTGS2 showing a 6.437 ± 0.81 folds increase (P < 0.0001). Furthermore, key regulators such as SLC7A11 and GPX4 proteins exhibited a reduction of 97.33 ± 25.78% (P = 0.0068) and 60.59 ± 14.93% (P = 0.0071), respectively, indicating the occurrence of ferroptosis following the surgery. Ferroptosis exists in myocardial IR injury caused by cardiac surgery with CPB, indicating that targeting ferroptosis could serve as a potential strategy for myocardial protection against CPB-induced IR injury. The trial has been registered in Chinese Clinical Trial Registry (ChiCTR, No. ChiCTR2200061995) on July 16th, 2022.

[Analysis of death characteristics and its potential mechanisms in rats with endotoxin- induced cardiomyopathy].

OBJECTIVE: To approach the changes in heart failure and dying regularity of rats with endotoxin-induced cardiomyopathy, and to offer some help for clinical diagnosing and further investigation. METHODS: Injecting refined endotoxin (10 mg/kg) via vein of Wistar rats. The first experiment: antidromic observing the endotoxic rats from death to the beginning to discover the performance of clinic heart function which could forecast death. The second experiment: setting 6 rats per group, respectively killing the rats at 4, 8, 16, 24, 32, 40, 48 and 72 hours after endotoxin injection, and killing 6 normal rats as control group, getting the tissue of left ventricle for biochemistry test, routine pathological examination, transmission electron microscope examination, expression level of α(1)-actin gene with reverse transcription-polymerase chain reaction (RT-PCR), and serum creatine kinase (CK) was test within 24 hours. RESULTS: The first experiment: heart rate (HR) and left ventricular end-systolic pressure (LVESP) of endotoxic rats began significant lower than normal at 4 hours before death (F(1)=22.032, P(1)=0.000; F(2)=29.420, P(2)=0.000), maximum rate of rise/drop of left ventricular pressure (±dp/dt max) began significant lower than normal at 8 hours before death (F(1)=17.272, P(1)=0.000; F(2)=19.685, P(2)=0.000), left ventricular end-diastolic pressure (LVEDP) showed no significant during the whole time (F=0.265, P=0.988). The heart function of all the rats showed no significant changes in the first 4 hours after injection. Mortality was 73.9% from injection to 24 hours later. Most of them died in 8-16 hours after injection. The one who had survived over 24 hours could have 2/3 probability to survive to 48 hours. The second experiment: CK in serum of different groups showed no significant difference (F=0.402, P=0.805), but showed obvious discreteness in each group except normal group. Electron microscopy and pathological examination showed obvious intracellular and intercellular damage since 8 hours later from injection. Pathology displayed that cells range disorder, mitochondria swelling, capillary hemorrhage, transverse striation disappearing, construction of myocardial cell loosing, and lateral dissociation phenomena. Electron microscopy discovered that the fiber direction and transverse striation became vague and disappeared, mitochondria got injury, the fiber became disordered, cell-cell junction were damaged seriously. Compared with the control group (0.637±0.160), the gene expression level of α(1)-actin decreased after endotoxin injection. The value dropped to the bottom at 8 hours (0.493±0.067) after injection and then rised slowly but dropped to the second wave trough again at 32 hours (0.875±0.128), but had no statistic significance; the expression of α(1)-actin gene eventually rised significantly at 40, 48, 72 hours after injection (2.231±0.545, 1.850±0.436, 2.062±0.340, all P<0.01). CONCLUSIONS: Endotoxic myocardiopathy does not result from plasmalemma destroy. Damage of α(1)-actin is a significantly important factor for endotoxic myocardiopathy.

LncRNA XIST promotes myocardial infarction by regulating FOS through targeting miR-101a-3p.

The purpose of this study was to reveal the hypothesis that lncRNA X inactive specific transcript (XIST) can participate in the regulation of cardiomyocyte apoptosis in neonatal mice cardiomyocytes (NMCMs) and myocardial infarction (MI) through targeting miR-101a-3p. NMCMs were isolated from neonatal C57BL/6 mice and anoxia was induced in hypoxic chamber. MTT assay and flow cytometry were used to determine proliferation and apoptosis respectively. The target relationship among XIST, miR-101a-3p and FOS was revealed by bioinformatic analysis, luciferase reporter assay, pull-down assay and RNA immunoprecipitation assay. The expression of XIST, miR-101a-3p, FOS and apoptosis-related proteins was determined by qRT-PCR or western blot. MI model was constructed to reveal the role of XIST. We found that XIST was up-regulated in NMCMs under anoxia condition. Moreover, XIST increased FOS expression by sponging miR-101a-3p in anoxia cells. Silencing XIST expression improved cell viability and suppressed apoptosis in vitro and inhibited myocardial infarction by reducing the level of c-FOS and apoptosis-related proteins in vivo. Our findings suggest that XIST is involved in MI, modulation of its level can be used as a new strategy or potential target in the treatment of myocardial infarction.

Sirt1 improves heart failure through modulating the NF-κB p65/microRNA-155/BNDF signaling cascade.

Heart failure (HF) affects over 26 million people worldwide, yet the pathologies of this complex syndrome have not been completely understood. Here, we investigated the involvement of deacetylase Sirtuin 1 (Sirt1) in HF and its downstream signaling pathways. A HF model was induced by the ligation of the left coronary artery in rats, where factors associated with left ventricular echocardiography, heart hemodynamics and ventricular mass indexes were recorded. Collagen volume fraction in heart tissues was determined by Masson's trichrome staining. Cell models of HF were also established (H2O2, 30 min) in cardiomyocytes harvested from suckling rats. HF rats presented with downregulated expressions of Sirt1, brain-derived neurotrophic factor (BDNF) and exhibited upregulated expressions of NF-κB p65 and miR-155. Repressed Sirt1 expression increased acetylation of NF-κB p65, resulting in the elevation of NF-κB p65 expression. NF-κB p65 silencing improved heart functions, decreased ventricular mass and reduced apoptosis in cardiomyocytes. MiR-155 inhibition upregulated its target gene BDNF, thereby reducing cardiomyocyte apoptosis. Sirt1 overexpression upregulated BDNF, improved heart function, and reduced apoptosis in cardiomyocytes. In conclusion, Sirt1 alleviates HF in rats through the NF-κB p65/miR-155/BDNF signaling cascade.

An integration-free iPSC line ZZUNEUi008-A derived from dermal fibroblasts of a child with cardiac valvular dysplasia carrying a mutation in FLNA gene.

FLNA gene encodes an actin-binding protein filamin A and mutations in FLNA can causes X-Linked cardiac valvular dysplasia. In this study, we report the generation of ZZUNEUi008-A, a human induced pluripotent stem cell line from a 10-year-old male patient with c. 84G â†’ A in FLNA gene using non-integrative Sendai viral reprogramming technology. The ZZUNEUi008-A iPSC line expresses pluripotency markers, exhibits a normal male karyotype (46, XY) and can differentiate into three germ layers in vivo.

Cardioprotective effects of microRNA-18a on acute myocardial infarction by promoting cardiomyocyte autophagy and suppressing cellular senescence via brain derived neurotrophic factor.

BACKGROUND: The prevention of cardiovascular diseases is a matter of great concern, of which acute myocardial infarction (AMI) remains one of the leading causes of death resulting in high morbidity worldwide. Emerging evidence highlights the importance of microRNAs (miRNAs) as functional regulators in cardiovascular disease. In this study, an AMI rat model was established in order to investigate the effect of miR-18a on cardiomyocyte autophagy and senescence in AMI and the underlying mechanism. METHODS: In the present study, an AMI model was induced by ligating the anterior descending branch of left coronary artery in Wistar rats. Dual-luciferase reporter gene assay was introduced for exploration on the relationship between miR-18a and brain derived neurotrophic factor (BDNF). The gain- and loss-of-function experiments were performed to elucidate miR-18a and BDNF effects on cell autophagy and senescence in AMI by transfecting hypoxia-exposed H9c2 cells with miR-18a inhibitor or mimic, siRNA against BDNF, or hypoxia-exposed H9c2 cell treatment with an agonist of the Akt/mTOR axis (LM22B-10). RESULTS: Upregulation of miR-18a was found in AMI, while downregulation was present in BDNF to activate the Akt/mTOR axis. Compared with the miR-18a inhibitor group, the expression of p-Akt and p-mTOR increased and the number of senescent cells increased in the miR-18a inhibitor + LM22B-10 group, and the expression of Beclin1, LC3-II, p62 decreased and autophagy decreased (all p < 0.05). Furthermore, this could be rescued by knocking down BDNF or Akt/mTOR axis activation by LM22B-10. CONCLUSION: All in all, downregulation of miR-18a could promote BDNF expression, which offers protection against AMI by inactivating the Akt/mTOR axis, highlighting a promising therapeutic strategy for AMI treatment.

Retracted Article: Long noncoding RNA ANRIL protects cardiomyocytes against hypoxia/reoxygenation injury by sponging miR-195-5p and upregulating Bcl-2.

Long noncoding RNAs have been widely accepted to play important roles in acute myocardial infarction (AMI). The dysregulation of cyclin-dependent kinase inhibitor 2B antisense RNA 1 (ANRIL) was discovered in AMI patients. Nevertheless, the detailed role and molecular mechanisms of ANRIL in AMI remain indistinct. The levels of ANRIL, miR-195-5p and Bcl-2 mRNA were determined by qRT-PCR. western blot was performed to assess the expression of Bcl-2, Bax, Cyclin D1 and p21. Cell proliferation was detected by CCK-8 assay, and cell apoptosis was measured by flow cytometry. The targeted correlation between ANRIL and miR-195-5p was confirmed by the dual-luciferase reporter and RNA pull-down assays. Our data revealed that ANRIL was downregulated and miR-195-5p was upregulated in the serum of AMI patients and hypoxia/reoxygenation (H/R)-induced myocardial cells. ANRIL upregulation or miR-195-5p knockdown alleviated H/R-induced myocardial cell injury. Moreover, ANRIL sequestered miR-195-5p by acting as a sponge of miR-195-5p. ANRIL upregulated Bcl-2 expression by sponging miR-195-5p. Additionally, ANRIL overexpression alleviated H/R-induced myocardial cell injury by upregulating Bcl-2. In conclusion, our study indicated that ANRIL upregulation alleviated H/R-induced myocardial cell injury partially through sponging miR-195-5p and upregulating Bcl-2, highlighting its role as a promising mediator for new therapies for AMI treatment.

Comparison of anticoagulant effects on vein grafts between human TFPI gene transfection and aspirin oral administration.

To develop a more efficient antithrombotic way after coronary artery bypass grafting (CABG), the anticoagulant effects were compared of human tissue factor pathway inhibitor (TFPI) gene transfection and aspirin oral administration (traditional method) on vein grafts. An eukaryotic expression plasmid pCMV-(Kozak) TFPI was prepared. Animal model of carotid artery bypass grafting was constructed. In operation, endothelial cells of vein grafts in TFPI group and empty plasmid control group were transfected with pCMV-(Kozak) TFPI and empty plasmid pCMV respectively, while no transfection was conducted in aspirin control group. After operation, aspirin (2 mg.kg(-1).(-1)) was administered (i.g.) in aspirin control group. Three days later, grafts (n=10) were harvested for RT-PCR, Western blotting and immunohistochemical analyses of exogenous gene expression and for pathological, scanning electron microscopic observation of thrombus. Thirty days later, the patency rates of remnant grafts (n=10) were recorded by vessel Doppler ultrasonography. Human TFPI gene products were detected in gene transferred vein grafts. Three days later, thrombi were found in 7 animals of aspirin control group and in 8 animals of empty plasmid control group, but in only 1 of TFPI group (P<0.01). Thirty days later, 5 grafts were occluded in empty plasmid control group, but none of grafts was occluded in the other groups (P<0.05). The endothelial surfaces of grafts in both of the control groups were covered with aggregated erythrocytes and platelets, and it were not seen in TFPI group. It was suggested that the anticoagulant effects on vein grafts of human TFPI gene transfection are better than those of aspirin.

Effect of thrombelastography on timing of coronary artery bypass grafting.

The guiding value of thrombelastography (TEG) on the selection of surgical timing for patients scheduled for coronary artery bypass grafting (CABG) was investigated. A total of 90 subjects with acute coronary syndrome (ACS) treated between February 2014 and December 2016 in Henan Provincial People's Hospital were recruited. The patients received dual antiplatelet therapy (DAPT) and were scheduled for CABG. Subjects were randomly allocated into two groups, TEG group (n=45) and non-TEG group (n=45). Patients in the TEG group withheld medications at 24 h prior to surgery and received TEG examination. Based on maximum amplitude of adenosine diphosphate (MAADP), subjects were further grouped into three sub-groups with MAADP <35 mm, 35-50 mm, and >50 mm, and accordingly received CABG within 1 day, 3-5 days and 5 days later, respectively. Subjects in the control group (non-TEG group) received CABG 5-7 days after medication withdrawal. Chest drainage volume within 24 h after surgery and red blood cell transfusion during perioperative period were compared. Other recorded parameters were incubation period, intensive care unit length of stay, hospital stay, incidence of 30-day adverse events and readmission rate. The average waiting time before CABG for patients of TEG group was shorter compared with the commonly recommended time. The red blood cell transfusions during perioperative period of subjects in TEG group and non-TEG group were significantly different (P=0.23). The median hospital stay of subjects in TEG group was shorter than that of non-TEG group (P=0.037). The bleeding amount of patients in TEG group was 220.16±80.56 ml, which was significantly lower than that of non-TEG group (435.29±90.16). The difference was statistically significant (P=0.032). The results suggested that TEG assay-based evaluation of platelet function for patients scheduled for CABG reasonably guides surgeons with appropriate surgical timing and reduces the amount of time patients wait to be treated.

The protective role of p72 in doxorubicin­induced cardiomyocytes injury in vitro.

p72 (probable ATP-dependent RNA helicase DDX17) belongs to the DEAD­box RNA helicase family. p72 is important in RNA processing. Thus, the role of p72 in doxorubicin (DOX)­induced cardiomyocyte injury was investigated in the present study. The changes in p72 expression levels were studied in cultured neonatal cardiomyocytes and p72 overexpression was induced using adenovirus vectors. To investigate the production of reactive oxygen species (ROS), dihydroethidium staining was conducted. TUNEL and Hoechst staining were used to indicate cell apoptosis. Microarrays were used to determine the altered expression of microRNAs. In DOX­induced cardiomyocyte injury, the protein expression level of p72 was reduced. Overexpression of p72 protected cardiomyocytes from DOX­induced ROS production and cell apoptosis. p72 reduced the activation of estrogen receptor α (ERα), thereby reducing DOX­induced cell apoptosis. The present study indicated that p72 exerts a protective effect against DOX­induced cell apoptosis via inhibition of ERα activation, indicating this may be a potential target of therapy for cardiac injury.

Ultrasonography, X-ray and CT imaging findings of a giant pericardial lipoma: Imaging diagnosis and review of the literature.

Pericardial lipomas are rare and mostly asymptomatic tumors, which are usually detected incidentally during physical examination. The present study describes a case of giant pericardial lipoma that was diagnosed by surgical pathology. The study also describe the X-ray, magnetic resonance imaging, and the distinguish of the pericardial lipomas. The study also describes the ultrasonography, X-ray, computed tomography and magnetic resonance imaging findings of the tumor, and a review of the literature of cardiac lipoma, to help increase awareness of the tumor and selection of the correct imaging method for diagnosis.

[Changes of thyroxin and monocyte human leukocyte antigen-DR expression in senior patients with sepsis].

OBJECTIVE: To investigate the changes of thyroxin and monocyte human leukocyte antigen-DR expression in senior patients with sepsis and explore their clinical significance. METHODS: According to the 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions, 125 senior patients with sepsis free of thyroid conditions were divided into non-severe sepsis group (n=86) and severe sepsis group (n=39), with another 30 healthy subjects as the control. Thyroid function was assayed by chemoluminescence method in these patients and monocyte HLA-DR expression was determined by flow cytometry. RESULTS: Compared with the control group and non-severe sepsis cases, the levels of free T3 (FT3), free T4 (FT4), T3, T4 and monocyte HLA-DR expression were significantly lower in severe sepsis cases (P<0.05), but the levels of thyroid stimulating hormone (TSH) were comparable between the 3 groups (P>0.05). The non-severe sepsis cases showed significantly lower levels of FT3, FT4, T3, T4, TSH and monocyte HLA-DR expression than the control group (P<0.05). In severe sepsis group, the levels of FT3, FT4, T3, T4 and monocyte HLA-DR expression showed significant differences between the fatal cases and surviving cases (P<0.05). CONCLUSION: The levels of thyroxin and monocyte human leukocyte antigen-DR expression are obviously lower in senior patients with severe sepsis, and their detection may well indicate the severity of the condition and help make prognostic judgment.

[Changes in the mRNA expressions of myocardial cytoskeletal proteins in endotoxemic rats].

OBJECTIVE: To investigate the changes of the mRNA expressions of myocardial cytoskeletal proteins in endotoxemic rats. METHODS: Thirty-seven Wistar rats were randomized into two groups with injection of 10 mg/kg lipopolysaccharide (LPS) or normal saline through the femoral vein. The cardiac function of the rats was monitored continuously for 24 h, and the morphological changes of the cardiac myocytes were observed with HE staining and electron microscope. The mRNA levels of myocardial cytoskeletal proteins including actin, tubulin and desmin were determined by RT-PCR. RESULTS: No significant difference was found in the number of CD3(+)T lymphocytes in the TILs between different groups. After the immunotherapy, the peLPS injection resulted in significant impairment of the cardiac function and myocardial microstructure of the rats with reduced heart rate and left ventricular systolic pressure (LVSP). The mRNA expression of actin in the cardiac myocytes measured by fluorescence optical density was reduced significantly 8 h after LPS injection, and that of tubulin was decreased significantly 24 h after LPS treatment; desmin mRNA expression showed no significant variation after LPS injection. CONCLUSION: LPS can significantly impair the cardiac function of the rats possibly by inducing damages of the myocardial cytoarchitecture and causing changes in the mRNA expressions of such cytoskeletal proteins as actin and tubulin.

[Therapeutic effect of low-dose thyroxin in elderly patients with refractory heart failure and euthyroid sick syndrome].

OBJECTIVE: To investigate the therapeutic effect of low-dose thyroxin in elderly patients with refractory heart failure (RHF) and euthyroid sick syndrome (ESS). METHODS: Fifty-four elderly patients with RHF and ESS were randomized into conventional treatment group (n=32) and L-thyroxine group with additional oral L-thyroxine at the daily dose of 6.25-25 microg (n=22). The changes in the plasma levels of brain natriuretic peptides (BNP), left ventricular ejection fraction (LVEF), and cardiac function (NYHA level) of the two groups were compared after 1 month of treatment. RESULTS: Five patients receiving conventional treatment died due to severe arrhythmia during the treatment, and in the other 27 patients, the levels of plasma BNP, LVEF, and cardiac function showed no significant improvements after 1 month of treatment (P>0.01). In L-thyroxine group, no death or severe arrhythmia occurred, and the levels of plasma BNP, LVEF, and cardiac function were significantly improved after the treatment (P<0.01). No thyrotoxicosis occurred during the administration of L-thyroxine in the latter group. CONCLUSION: Low-dose L-thyroxine in addition to the conventional treatments may enhance the therapeutic effect in elderly patients with RHF and ESS.

Comparison of Anticoagulant Effects on Vein Grafts between Human TFPI Gene Transfection and Aspirin Oral Administration / 华中科技大学学报（医学）（英德文版）

To develop a more efficient antithrombotic way after coronary artery bypass grafting (CABG), the anticoagulant effects were compared of human tissue factor pathway inhibitor (TFPI) gene transfection and aspirin oral administration (traditional method) on vein grafts. An eukaryotic expression plasmid pCMV-(Kozak) TFPI was prepared. Animal model of carotid artery bypass grafting was constructed. In operation, endothelial cells of vein grafts in TFPI group and empty plasmid control group were transfected with pCMV-(Kozak) TFPI and empty plasmid pCMV respectively, while no transfection was conducted in aspirin control group. After operation, aspirin (2 mg·kg-1·d-1) was administered (I.g.) in aspirin control group. Three days later, grafts (n=10) were harvested for RT-PCR, Western blotting and immunohistochemical analyses of exogenous gone expression and for pathological, scanning electron microscopic observation of thrombus. Thirty days later, the patency rates of remnant grafts (n=10) were recorded by vessel Doppler ultrasonography. Human TFPI gene products were detected in gene transferred vein grafts. Three days later, thrombi were found in 7 animals of aspirin control group and in 8 animals of empty plasmid control group, but in only 1 of TFPI group (P<0.01). Thirty days later, 5 grafts were occluded in empty plasmid control group, but none of grafts was occluded in the other groups (P<0.05). The endothelial surfaces of grafts in both of the control groups were covered with aggregated erythrocytes and platelets, and it were not seen in TFPI group. R was suggested that the anticoagulant effects on vein grafts of human TFPI gene trans- fection are better than those of aspirin.