An echocardiogram-based 16-segment model for predicting left ventricular ejection fraction improvement

An important goal of cardiac revascularization is to improve the left ventricular ejection fraction, which is an important clinical determinant of the long-term outcome for patients with coronary artery disease. Regional myocardium function improvement may be expected from revascularization when viable myocardium is detected using non-invasive cardiac imaging. However, the quantitative relation between regional myocardial function recovery and global heart function improvement has not been determined and there is no tool to predict the amount of ejection fraction improvement prior to revascularization. A 16 segment biomechanical model of the left ventricle is proposed to establish the relationship between the ejection fraction improvement and the viable segments detected by echocardiography. With the assumption that the viable segments would potentially improve contractility after revascularization, the ejection fraction improvement is estimated for all possible wall motion score improvement in viable segments. The model shows that the ejection fraction improvement is linearly related to the contractility in the normal segments and a weighted sum of the numbers of viable segments that recover to normal or hypokinetic contractility. The predictive value of the model is illustrated for a group of patients reported in the literature. The model predictions of the post-revascularization ejection fraction are very close to the follow-up data with a very strong correlation (R2 = 0.92). By predicting the ejection fraction improvement, the model may provide a tool for evaluating the efficacy of revascularization and for selecting patients who would benefit from revascularization.     

血管内皮生长因子(VEGF)乳液法电纺纤维膜的体外研究

目的:研究担载血管内皮生长因子(VEGF)的乳液法电纺纤维膜的亲水性能、外观形态和机械性能,纤维膜中VEGF的包封率和体外释放动力学,为评价其能否应用于血管再生领域的研究奠定基础。方法:将VEGF水溶液通过W/O乳液法制备成缓释VEGF的生物可降解的丙交酯-乙交酯共聚物(PLGA)静电纺丝纤维膜,对该纤维膜的接触角、外观形态、机械性能进行表征,Elisa法测定该纤维膜的体外14天的释放行为,分别观察纤维膜释放0天、7天、14天后的电镜图。结果:加入VEGF后,纤维膜的接触角由140.0°减小到136.1°,亲水性增强,具有类似细胞外基质(ECMs)网状结构和良好的力学性能,纤维膜第1天的突释不超过载药量的50%,电镜图下显示纤维膜释放1周时纤维发生断裂。结论:通过乳液法制备的担载VEGF的电纺纤维膜具有良好的物理性能,能够持续缓释VEGF,可作为血管再生的组织工程支架进行深入研究。     

Therapeutic effect of autologous bone marrow stem cell mobilization combined with anti-infective therapy on moyamoya disease

ObjectiveThe purpose of this study is to explore the therapeutic effect of autologous bone marrow stem cell (ABMSC) mobilization combined anti-infection therapy on patients with moyamoya disease (MMD), and to provide reference for the clinical treatment of MMD and cerebrovascular disease.Methods54 adult patients with MMD diagnosed in Henan Provincial People’s Hospital from March 2017 to March 2019 were chosen as research objects. All patients were randomly divided into study group (SG) and control group (CG), with 27 patients in each group. Patients in both groups received conventional drug treatment after diagnosis of MMD, and received dura turnover of brain - temporal muscle - superficial temporal artery application surgery during indirect vascular reconstruction. On the basis of surgical treatment, patients in the SG were given ABMSC mobilization combined with low-dose dexamethasone for anti-inflammatory and anti-infection treatment. ABMSCs were mobilized by recombinant human granulocyte colony stimulating factor (rhG-csF) and recombinant human granulocyte - macrophage colony stimulating factor (rhoM-esF). The therapeutic effects of the patients were evaluated BF, one month after treatment (AF), three months AF, and six months AF. The number of hematopoietic stem cells (HpCs) and inflammatory indicators were compared between the two groups before and 4 weeks AF.ResultsFirstly, the Barthcl index of patients in the two groups showed a gradual increase trend at the 3rd and 6th months AF, and the ascensional range in the research group was higher than that in the CG (P < 0.05). Secondly, at the 3rd and 6th month AF, national institute of heath stroke scale (NIHSS) scores of patients in the CG were lower than those before treatment (BF), and there was an important change in NIHSS scores between the two groups at the same period (P < 0.05). Thirdly, after 1 month of treatment and 3 months of treatment, Chinese stroke scale (CSS) scores of patients in both groups decreased obviously compared with those BF, and the SG was lower than the CG, with statistical changes (P < 0.05). Fourthly, after 4 weeks of treatment, the hematopoietic stem cell counts in both groups were higher than those BF, and the hematopoietic stem cell counts in the SG were obviously higher than those in the CG (P < 0.05). All three inflammatory indicators were improved compared with those BF, and the SG was better than the CG (P < 0.05).ConclusionAutogenous bone marrow stem cell mobilization combined with dexamethasone anti-inflammation and anti-infection treatment after revascularization in patients with MMD can accelerate the recovery of nerve function and promote the formation of new blood vessels. At the same time, it can reduce inflammation and improve patients' quality of life, which is worthy of clinical reference.     

The role of angiogenesis and pulpal healing in tooth replantation and allograft transplantation

Tooth transplantation is one of the treatment options for extracted teeth that can be considered before dental implantation. Although the success rate of tooth transplantation is lower than that of implantation, tooth replantation and transplantation have the great advantage of using natural teeth. Tooth replantation might be considered a promising option in some cases. In present study, the expression patterns of revascularization and pulpal healing, which are the most important for the pulp viability, were analyzed after tooth replantation and allograft in mice. The inflammatory response and root dentin resorption were observed and not different between replantation and allograft in initiation of healing process. However, bonelike tissue formation, pulp revascularization and pulp healing were faster in replantation. The difference of healing patterns between tooth replantation and allograft found in present study will be helpful to select the treatment option and to understand healing mechanism.     

急性ST 段抬高心肌梗死患者多支病变血运重建治疗策略的临床研究

目的:分析急性ST段抬高心肌梗死(acute ST segmentelevation myocardial infarction,STEMI)伴多支血管病变行急诊经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗的策略,制定患者血运重建时机及最佳方案。方法:收集2008.10-2012.10期间急性ST段抬高心肌梗死伴多支血管病变行急诊PCI治疗患者资料,其中仅行罪犯血管PCI治疗组162例,多支血管PCI治疗组50例、阶段PCI治疗组112例,分析比较各组间短期(3个月)死亡率和1年、2年、3年死亡率及主要心血管事件(major cardiovascularevents,MACE)发生率。结果:①多支血管PCI组较罪犯血管PCI组有更高的短期死亡率(4.0%vs 2.5%,P0.05),但其降低MACE发生率(12.0%vs 15.4%,P0.05);②阶段PCI组较罪犯血管PCI组有更低的死亡率(短期和1年、2年、3年死亡率均P0.05)及MACE发生率(11.6%vs 15.4%,P0.05);③多支血管PCI组较阶段PCI组有更高的短期死亡率(4.0%vsl.8%,P0.05),长期随访无明显不同(6.0%vs 5.4%,P0.05);MACE的发生率无明显差异(12.0%vs 11.6%,P0.05)。结论:当血流动力学稳定时,合并多支血管病变的急性ST段抬高心肌梗死仅对罪犯血管行PCI,随后行阶段PCI处理非梗死病变血管,这一策略能显著改善患者的临床预后。     

Non-neuronal nicotinic alpha 7 receptor, a new endothelial target for revascularization

Alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) is widely expressed in the central and peripheral nervous systems, and is also found in several non-neuronal tissues, such as endothelial cells (ECs), bronchial epithelial cells, skin keratinocytes and vascular smooth muscle cells. Recent evidence suggests that alpha7 nAChR is involved in angiogenesis. Here, we investigated the feasibility of alpha7 nAChR for revascularization in ischemic heart disease. RT-PCR and immunohistochemistry were used to examine the expression of alpha7 nAChR in human umbilical vein endothelial cell (HUVECs). The cellular function was examined using MTT, fluorescence confocal microscopy and angiogenesis assay in vitro. The capillary density in the rat model of myocardial infarction (MI) was investigated using immunohistochemistry. The results showed that alpha7 nAChR agonists choline increased the expression of alpha7 nAChR mRNA and protein, the intracellular Ca 2+ concentration, proliferation and tube formation of ECs. Reverse effects were observed by using alpha7 nAChR antagonist alpha-BTX. Furthermore, in the rat model of MI, alpha7 nAChR agonist enhanced the capillary density in ischemic tissues, whereas antagonist mecamylamine and alpha-BTX inhibited the effect. Our results suggest that alpha7 nAChR is involved in the regulation of cellular function in ECs, and capillary formation in MI, which are the important steps of angiogenesis. Therefore, alpha7 nAChR on ECs may be a new endothelium target for revascularization in therapeutic angiogenesis of ischemic heart disease.     

Finite-element Analysis of a Stenotic Artery Revascularization Through a Stent Insertion

Short-term and long-term clinical follow-up data clearly indicate the superiority of stenting techniques within the family of mechanical treatments for percutaneous coronary revascularizations. However, restenosis phenomena are in general still present, representing the major drawback for this innovative non-invasive approach.

Experimental evidence indicates the mechanical interaction between the stent and the artery as a significant cause for the activation of stent-related restenosis. At the same time, the literature shows a significant lack of computational investigations within this field, possibly as consequence of the complexity of the problem.

According to these considerations, the aim of the present work is to study the bio-mechanical interaction between a balloon-expandable stent and a stenotic artery, highlighting considerations able to improve the general understanding of the problem.

In particular, given an initial stent design (J&J Palmaz-Schatz like), we show the presence of possible areas of artery injury during the stent deployment and areas of non-uniform contact pressure after the stent apposition, due to a non-uniform stent expansion. Since these concentrated mechanical actions can play an important role in the activation of restenosis mechanisms, we propose a modified stent design, which shows a more uniform expansion and for which typical stenting parameters (i.e., residual stenosis, elastic recoil, foreshortening) are computed and presented.     

Fat-derived factor omentin stimulates endothelial cell function and ischemia-induced revascularization via endothelial nitric oxide synthase-dependent mechanism

Obesity-related diseases are associated with vascular dysfunction and impaired revascularization. Omentin is a fat-derived secreted protein, which is down-regulated in association with obese complications. Here, we investigated whether omentin modulates endothelial cell function and revascularization processes in vitro and in vivo. Systemic delivery of an adenoviral vector expressing omentin (Ad-omentin) enhanced blood flow recovery and capillary density in ischemic limbs of wild-type mice in vivo, which were accompanied by increased phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). In cultured human umbilical vein endothelial cells (HUVECs), a physiological concentration of recombinant omentin protein increased differentiation into vascular-like structures and decreased apoptotic activity under conditions of serum starvation. Treatment with omentin protein stimulated the phosphorylation of Akt and eNOS in HUVECs. Inhibition of Akt signaling by treatment with dominant-negative Akt or LY294002 blocked the stimulatory effects of omentin on differentiation and survival of HUVECs and reversed omentin-stimulated eNOS phosphorylation. Pretreatment with the NOS inhibitor also reduced the omentin-induced increase in HUVEC differentiation and survival. Omentin protein also stimulated the phosphorylation of AMP-activated protein kinase in HUVECs. Transduction with dominant-negative AMP-activated protein kinase diminished omentin-induced phosphorylation of Akt and omentin-stimulated increase in HUVEC differentiation and survival. Of importance, in contrast to wild-type mice, systemic administration of Ad-omentin did not affect blood flow in ischemic muscle in eNOS-deficient mice in vivo. These data indicate that omentin promotes endothelial cell function and revascularization in response to ischemia through its ability to stimulate an Akt-eNOS signaling pathway.     

LKB1 Deficiency in Tie2-Cre-expressing Cells Impairs Ischemia-induced Angiogenesis

LKB1 is a tumor suppressor protein whose loss leads to HIF1α-mediated activation of a proangiogenic program in intestinal polyps. LKB1 is also protein kinase regulator of AMP-activated protein kinase (AMPK) signaling, which is essential for endothelial cell responses to tissue ischemia. To discern whether LKB1 signaling is either pro- or antiangiogenic, we investigated ischemia-induced revascularization in mice that were deficient for LKB1 in Tie2-Cre-expressing cells. Whereas homozygous deletion of LKB1 led to embryonic lethality, heterozygous LKB1-knock-out (KO) (Lkb1^flox/+;Tie2^Tg/+) mice were viable. Unchallenged heterozygous LKB1-KO mice displayed normal capillary density, but the revascularization of hind limb following ischemic surgery was significantly impaired as evaluated by laser Doppler flow and capillary density measurements. Reduction of LKB1 in cultured endothelial cells, using either small interfering RNA or an adenovirus expressing nonfunctional kinase-dead LKB1 protein, attenuated endothelial proliferation, migration, and differentiation into network structures on Matrigel that was accompanied by diminished AMPK phosphorylation at Thr-172. Conversely, adenovirus-mediated LKB1 overexpression (Ad-LKB1) augmented network structure formation, and this was associated with elevated AMPK phosphorylation. The augmented differentiation of endothelial cells into network structures induced by Ad-LKB1 was abrogated by the co-transduction of a dominant negative mutant of AMPK. These observations suggest that the LKB1-AMPK signaling axis in endothelial cells is a positive regulator of the revascularization response to tissue ischemia.     

血运重建程度与不稳定心绞痛患者经皮冠状动脉介入术后早期预后的相关性

目的:探讨合并左主干/三支病变的不稳定型心绞痛患者的血运重建程度(revascularization extent,RE)及其早期预后的关系。方法:回顾性分析自2012年1月1日-2012年12月31日期间就诊于解放军总医院心血管内科行经皮冠状动脉介入术(Percutaneous Coronary Intervention,PCI)的不稳定型心绞痛患者201例,按其血运重建程度分为三组:低血运重建程度组(Low RE group,RE≤65%),中等血运重建程度组(Medium RE group,65%RE85%),高血运重建程度组(High RE group,RE≥85%),比较三组患者PCI术后主要不良心脑血管事件(Major Adverse Cardiac and Cerebral Events,MACCE)的发生情况。结果:血运重建程度RE是不稳定型心绞痛合并左主干/三支病变患者MACCE及再次血运重建的独立预测因子;随着RE的降低,不稳定型心绞痛合并左主干/三支病变患者MACCE(25.0%、9.1%、6.0%,log-rank p=0.002)及再次血运重建(22.1%、7.6%、4.5%,log-rank p=0.002)的发生率增加,而其死亡率及再梗死率的差异无统计学意义(P0.05)。结论:不稳定型心绞痛合并多支血管病变的患者,可行完全再血管化治疗,以减少术后早期再血管化事件率及MACCE事件发生率。