Sodium-Glucose Cotransporter 2 Inhibitors in Adult and Pediatric Congenital Heart Disease: Review of Emerging Data and Future Directions

Heart failure(HF)is common in patients with congenital heart disease(CHD)and there are limited medical therapies.Sodium-glucose cotransporter 2 inhibitors(SGLT2i)are a proven medical therapy in patients with acquired HF,though data are limited in patients with CHD.The aim of this review is to summarize the current evidence for use of SGLT2i in patients with CHD and identify future directions for study.In available publica-tions,SGLT2i in patients with CHD seem to be well tolerated,with similar side effect profile to patients with acquired HF.Improvement in functional capacity and natriuretic peptides are mixed,though there is a signal for potential reduction in HF hospitalizations.One prospective study in patients with systemic right ventricles showed an improvement in systolic function for patients already on maximal HF medical therapy.Though lim-ited,there is emerging data on use of SGLT2i in pediatric patients with CHD and HF.Future prospective studies are needed to evaluate for clinically meaningful endpoints,including HF hospitalization,as well as evaluate the hemodynamic impact in subtypes of CHD at high risk for HF.

Sodium-Glucose Cotransporter-2 Inhibitors: Who, When & How? Guidance for Use from a Multidisciplinary Practical Approach

Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) have transformed diabetes management by targeting renal glucose reabsorption. Designed initially as antidiabetic agents, their ability to lower blood glucose levels independently of insulin is well-documented. Beyond glycemic control, emerging research has unveiled their profound cardiorenal benefits. By inhibiting SGLT-2 protein, these drugs enhance glucose excretion in urine, reducing blood glucose levels. This mechanism has translated into significant cardiovascular and renal protection, establishing SGLT-2 inhibitors as pivotal in managing not only diabetes but also cardiovascular and renal diseases. Recent studies have illuminated the broader therapeutic potential of SGLT-2 inhibitors beyond diabetes. Evidence indicates their efficacy in managing heart failure, chronic kidney disease (CKD), and cardiovascular complications in individuals with or without diabetes. This expanded therapeutic landscape has catalyzed a paradigm shift in SGLT-2 inhibitor use, positioning them as key agents in the cardiorenal metabolic continuum. Moreover, their role in the secondary prevention of cardiovascular events and slowing CKD progression in T2DM patients has garnered considerable attention. This consensus-based review aims to offer practical guidance in an algorithmic approach to primary care healthcare professionals to optimize SGLT-2 inhibitors utilization and maximize their benefits. The review seeks to empower clinicians to effectively manage patients who may benefit from SGLT-2 inhibitor therapy by addressing common initiation barriers and optimizing treatment strategies. Additionally, it aims to raise awareness among primary care physicians regarding the multifaceted benefits of these medications and overcome clinical inertia in their adoption into routine clinical practice.

Ipragliflozin: A novel sodium-glucose cotransporter 2 inhibitor developed in Japan

Sodium-glucose cotransporter 2(SGLT2) inhibition induces glucosuria and decreases blood glucose levels in diabetic patients and lowers hypoglycemic risk. SGLT1 is expressed in the kidney and intestine; SGLT1 inhibition causes abdominal symptoms such as diarrhea and reduces incretin secretion. Therefore, SGLT2 selectivity is important. Ipragliflozin is highly selective for SGLT2. In type 2 diabetes mellitus(T2DM), urinaryglucose excretion increased to 90 g/24 h after 28 d of treatment with ipragliflozin 300 mg/d. Twelve weeks of ipragliflozin 50 mg/d vs placebo reduced glycated hemoglobin and body weight by 0.65% and 0.66 kg, respectively, in Western T2 DM patients, and by 1.3% and 1.89 kg, respectively, in Japanese patients. Ipragliflozin(highly selective SGLT2 inhibitor) improves glycemic control and reduces body weight and lowers hypoglycemic risk and abdominal symptoms. Ipragliflozin can be a novel anti-diabetic and antiobesity agent.

Rise of sodium-glucose cotransporter 2 inhibitors in the management of nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the Western world. It is more prevalent in male gender, and with increasing age, obesity, and insulin resistance. Besides weight loss, there are limited treatment options. The use of anti-diabetic medications has been studied with mixed results. In this review, we discuss the use of anti-diabetic medications in the management of NAFLD with a specific focus on sodium-glucose cotransporter 2 inhibitors. We shed light on the evidence supporting their use in detail and discuss limitations and future directions.

Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure

Three major cardiovascular outcome trials(CVOTs)with a new class of antidiabetic drugs-sodium-glucose cotransporter 2(SGLT2)inhibitors(EMPAREG OUTCOME trial with empagliflozin,CANVAS Program with canagliflozin,DECLARE-TIMI 58 with dapagliflozin)unexpectedly showed that cardiovascular outcomes could be improved possibly due to a reduction in heart failure risk,which seems to be the most sensitive outcome of SGLT2 inhibition.No other CVOT to date has shown any significant benefit on heart failure events.Even more impressive findings came recently from the DAPA-HF trial in patients with confirmed and well-treated heart failure:Dapagliflozin was shown to reduce heart failure risk for patients with heart failure with reduced ejection fraction regardless of diabetes status.Nevertheless,despite their possible wide clinical implications,there is much doubt about the mechanisms of action and a lot of questions to unravel,especially now when their benefits translated to nondiabetic patients,rising doubts about the validity of some current mechanistic assumptions.The time frame of their cardiovascular benefits excludes glucoselowering and antiatherosclerotic-mediated effects and multiple other mechanisms,direct cardiac as well as systemic,are suggested to explain their early cardiorenal benefits.These are:Anti-inflammatory,antifibrotic,antioxidative,antiapoptotic properties,then renoprotective and hemodynamic effects,attenuation of glucotoxicity,reduction of uric acid levels and epicardial adipose tissue,modification of neurohumoral system and cardiac fuel energetics,sodiumhydrogen exchange inhibition.The most logic explanation seems that SGLT2 inhibitors timely target various mechanisms underpinning heart failure pathogenesis.All the proposed mechanisms of their action could interfere with evolution of heart failure and are discussed separately within the main text.

Potential for sodium-glucose cotransporter-2 inhibitors in the management of metabolic syndrome: A systematic review and metaanalysis

BACKGROUND Landmark trials have established the benefits of sodium-glucose cotransporter-2 inhibitors(SGLT2-Is)in cardiovascular disease including heart failure with reduced and preserved ejection fraction and renal diseases regardless of the presence of diabetes mellitus.However,studies evaluating the role of SGLT2-Is in metabolic syndrome(MetS)are limited.AIM This study primarily aimed to evaluate the impact of SGLT2-Is on the components of MetS.METHODS Two independent reviewers and an experienced librarian searched Medline,Scopus and the Cochrane central from inception to December 9,2021 to identify placebo controlled randomized controlled trials that evaluated the impact of SGLT2-Is on the components of MetS as an endpoint.Pre-and post-treatment data of each component were obtained.A meta-analysis was performed using the RevMan(version 5.3;Copenhagen:The Nordic Cochrane Center,The Cochrane Collaboration).RESULTS Treatment with SGLT2-Is resulted in a decrease in fasting plasma glucose(–18.07 mg/dL;95%CI:-25.32 to–10.82),systolic blood pressure(–1.37 mmHg;95%CI:-2.08 to–0.65),and waist circumference(–1.28 cm;95%CI:-1.39 to–1.18)compared to placebo.The impact on highdensity lipoprotein cholesterol was similar to placebo(0.01 mg/dL;95%CI:-0.05 to 0.07).CONCLUSION SGLT2-Is have a promising role in the management of MetS.

Analgesic effect of intrathecal bumetanide is accompanied by changes in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain

Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.

Sodium glucose cotransporter 2 inhibitors:New horizon of the heart failure pharmacotherapy

Sodium-glucose cotransporter 2(SGLT2)inhibitors have gained momentum as the latest class of antidiabetic agents for improving glycemic control.Large-scale clinical trials have reported that SGLT2 inhibitors reduced cardiovascular outcomes,especially hospitalization for heart failure in patients with type 2 diabetes mellitus who have high risks of cardiovascular disease.Accumulating evidence has indicated that beneficial effects can be observed regardless of the presence or absence of type 2 diabetes mellitus.Accordingly,the Food and Drug Administration approved these agents specifically for treating patients with heart failure and a reduced ejection fraction.It has been concluded that canagliflozin,dapagliflozin,empagliflozin,or ertugliflozin can be recommended for preventing hospitalization associated with heart failure in patients with type 2 diabetes and established cardiovascular disease or those at high cardiovascular risk.In the present review,we explore the available evidence on SGLT2 inhibitors in terms of the cardioprotective effects,potential mechanisms,and ongoing clinical trials that may further clarify the cardiovascular effects of the agents.

Role of the Na^+/K^+/2Cl^- cotransporter NKCC1 in cell cycle progression in human esophageal squamous cell carcinoma

AIM: To investigate the role of Na+/K+/2Cl- cotransporter 1 (NKCC1) in the regulation of genes involved in cell cycle progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC).

Chances and risks of sodium-glucose cotransporter 2 inhibitors in solid organ transplantation:A review of literatures

Solid organ transplantation offers life-saving treatment for patients with endorgan dysfunction.Patient survival and quality of life have improved over the past few decades as a result of pharmacological development,expansion of the donor pool,technological advances and standardization of practices related to transplantation.Still,transplantation is associated with cardiovascular complications,of which post-transplant diabetes mellitus(PTDM)is one of the most important.PTDM increases mortality,which is best documented in patients who have received kidney and heart transplants.PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus,but also from specific posttransplant risk factors such as metabolic side effects of immunosuppressive drugs,post-transplant viral infections and hypomagnesemia.Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients.However,the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited.The favourable risk/benefit ratio,which is suggested by large-scale and long-term studies on new glucoselowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors,makes studies warranted to assess the potential role of these agents in the management of PTDM.

Mechanism Underlying Increase of the Serum Magnesium Concentration Observed Following Treatment with Sodium-Glucose Cotransporter 2 Inhibitors

Aim: The EMPA-REG OUTCOME study reported that the sodium-glucose cotransporter 2 inhibitor (SGLT2-i) suppressed cardiovascular (CV) events in patients with type 2 diabetes;we recently suggested that increase of the serum magnesium (Mg) by SGLT2-i’s can, in part, explain this reduction. The objective of this study was to elucidate the mechanism underlying the elevation of the serum Mg level induced by treatment with SGLT2-i’s. Methods: We analyzed the data of 37 patients with type 2 diabetes who underwent clinical evaluation and laboratory assessment at baseline and the end of 3 months. To investigate the relationship between the changes in the serum Mg concentrations during 3 months’ treatment (ΔMg) and other variables, we carried out simple linear regression analysis and multiple linear regression analysis. Results: Three months’ treatment with the SGLT2-i resulted in a significant improvement of the body weight (BW), BMI, hemoglobin A1c (HbA1c), and fasting plasma glucose levels. The serum Mg increased significantly. Simple linear regression analysis revealed an association between the ΔMg and the serum triglyceride, serum Mg at baseline, change of the BW (ΔBW), and change of the HbA1c. Multiple linear regression analysis revealed a significant association between the ΔMg and the serum Mg level at the baseline (r = -0.55, P Conclusion: Our study revealed that a lower serum Mg level at the baseline and BW reduction were significantly associated with an increase in the serum Mg following 3 months’ treatment with SGLT2-i’s.

Localization and vasopressin regulation of the Na^+-K^+-2Cl^- cotransporter in the distal colonic epithelium

AIM: To investigate whether Na+-K+-2Cl- cotransporter (NKCC2) is expressed in the mouse distal colonic epithelia and whether it is regulated by vasopressin in the colon.

Heterogeneity in cardiorenal protection by Sodium glucose cotransporter 2 inhibitors in heart failure across the ejection fraction strata:Systematic review and meta-analysis

BACKGROUND Gliflozins or Sodium glucose cotransporter 2 inhibitors(SGLT2i)are relatively novel antidiabetic medications that have recently been shown to represent favorable effects on patients’cardiorenal outcomes.However,there is shortage of data on potential disparities in this therapeutic effect across different patient subpopulations.AIM To investigate differential effects of SGLT2i on the cardiorenal outcomes of heart failure patients across left ventricular ejection fraction(LVEF)levels.METHODS Literature was searched systematically for the large randomized double-blind controlled trials with long enough follow up periods reporting cardiovascular and renal outcomes in their patients regarding heart failure status and LVEF levels.Data were then meta-analyzed after stratification of the pooled data across the LVEF strata and New York Heart Associations(NYHA)classifications for heart failure using Stata software version 17.0.RESULTS The literature search returned 13 Large clinical trials and 13 post hoc analysis reports.Meta-analysis of the effects of gliflozins on the primary composite outcome showed no significant difference in efficacy across the heart failure subtypes,but higher efficacy were detected in patient groups at lower NYHA classifications(I2=46%,P=0.02).Meta-analyses across the LVEF stratums revealed that a baseline LVEF lower than 30%was associated with enhanced improvement in the primary composite outcome compared to patients with higher LVEF levels at the borderline statistical significance(HR:0.70,95%CI:0.60 to 0.79 vs 0.81,95%CI:0.75 to 0.87;respectively,P=0.06).Composite renal outcome was improved significantly higher in patients with no heart failure than in heart failure patients with preserved ejection fraction(HFpEF)(HR:0.60,95%CI:0.49 to 0.72 vs 0.94,95%CI:0.74 to 1.13;P=0.04).Acute renal injury occurred significantly less frequently in heart failure patients with reduced ejection fraction who received gliflozins than in HFpEF(HR:0.67,95%CI:51 to 0.82 vs 0.94,95%CI:0.82 to 1.06;P=0.01).Volume depletion was consistently increased in response to SGLT2i in all the subgroups.CONCLUSION Heart failure patients with lower LVEF and lower NYHA sub-classifications were found to be generally more likely to benefit from therapy with gliflozins.Further research are required to identify patient subgroups representing the highest benefits or adverse events in response to SGLT2i.

Saudi Consensus on the Usage of Sodium-Glucose Cotransporter-2 Inhibitors on the Management of Chronic Kidney Diseases

According to recent epidemiological data, chronic kidney diseases (CKDs) affect approximately 10% of the global population. Like many countries, CKD is a significant public health issue in Saudi Arabia. The prevalence of CKD in Saudi Arabia is estimated to be around 4.5% of the adult population, with a higher prevalence in older age groups. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a class of oral medications used to treat type 2 diabetes mellitus (T2DM). In addition to their glucose-lowering effects, SGLT2i have been shown to have beneficial effects on kidney function in patients with or without T2DM. Therefore, a Saudi task force gathered to develop an explicit, evidence-based consensus on SGLT2i use in CKD Saudi patients. A panel of 14 experts made up a task force. An initial concept proposal was obtained. The proposal was divided into several topics discussed on 24 May 2023. A literature review was carried out. The literature search was completed on 3rd June 2023. A drafted report was distributed to the entire panel. Approval of the recommendations required consensus, defined as a majority approval (i.e. above 75%). The recommendations were revised to accommodate any differences of opinion until a consensus was reached. Recommendations were finally formulated on 21st June 2023. Subsequently, the panel reviewed and discussed the supporting rationale of the revised recommendations. This article presents these practical recommendations.

钠-葡萄糖协同转运蛋白2抑制剂对急性心肌梗死合并2型糖尿病患者临床指标及预后的影响

目的观察钠-葡萄糖协同转运蛋白2抑制剂(SGLT-2i)对急性心肌梗死(AMI)合并2型糖尿病(T2DM)患者临床指标及预后的影响。方法回顾性选取2020年1月至2022年6月于安徽医科大学第二附属医院胸痛中心就诊后确诊AMI合并T2DM患者180例,根据入院后降糖方案分为对照组(79例,给予磺脲类、α-糖苷酶抑制剂、二甲双胍等药物)和观察组(101例,给予达格列净或恩格列净)。患者出院后定期随访,比较2组患者临床指标及主要不良心血管事件(MACE)发生情况。结果所有患者随访6~12个月,结果显示观察组白细胞计数小于对照组[(7.4±1.6)×10^(9)/L比(8.7±1.6)×10^(9)/L],左心室舒张末期内径改善优于对照组[(-0.527±1.462)mm比(1.359±2.111)mm](均P<0.05)。观察组MACE发生率低于对照组[5.4%(2/37)比25.0%(8/32)],差异有统计学意义(P=0.020)。结论SGLT-2i较其他降糖药物12个月内能改善AMI合并T2DM患者的心脏功能及预后,且能减轻该类患者的全身炎症反应。

20例钠-葡萄糖共转运蛋白2抑制剂致福涅尔坏疽病例及文献分析

目的探讨钠-葡萄糖共转运蛋白2抑制剂(SGLT-2i)致福涅尔坏疽(FG)的发生特点,为临床安全用药提供参考。方法采用计算机检索PubMed、Embase、中国知网、万方、维普数据库自建库起至2023年6月有关SGLT-2i致FG的病例报道,并对相关数据进行统计和分析。结果共纳入20篇文献,涉及20例患者。其中,男14例(70.00%),女6例(30.00%);年龄(56.0±11.5)岁;12例(60.00%)描述为肥胖,其中5例为极重度肥胖(体质量指数不低于40 kg/m^(2))。FG发生中位时间为425 d,FG发生时糖化血红蛋白(HbA_(1C))平均值为9.2%。SGLT-2i致FG相关性为很可能的有8例,可能的有12例。20例患者经停药、及时清创引流及给予抗菌药物治疗后转归均良好。结论临床使用SGLT-2i时需注意识别其致FG的危险因素,一旦生殖器或会阴区域出现可疑的肿胀、疼痛等不适,需立即就医,并给予积极治疗。

SGLT-2抑制剂致成人2型糖尿病患者糖尿病酮症酸中毒风险的Meta分析

目的对钠—葡萄糖协同转运蛋白2(SGLT-2)抑制剂致成人2型糖尿病(T2DM)患者糖尿病酮症酸中毒(DKA)风险进行系统Meta分析。方法检索美国国立医学图书馆数据库、医学文摘数据库、Cochrane循证医学数据库从建库至2023年12月31日收录SGLT-2抑制剂治疗T2DM患者的随机对照试验。提取纳入文献的样本量、患者性别、年龄、体质量指数、发生DKA情况、治疗时间及药物种类。使用RevMan5.4版软件进行Meta分析,二分类变量以相对危险度(RR)值及95%CI作为效应量。结果最终共纳入26篇文献65176例T2DM患者,其中SGLT-2抑制剂治疗(观察组)37021例,对照组28155例;共发生DKA事件139例,观察组DKA事件发生率为0.29%(106/37021),对照组DKA事件发生率为0.12%(33/28155),观察组发生DKA风险显著高于对照组(RR=2.71,95%CI 1.84~3.97,P<0.001)。进一步亚组分析提示SGLT-2抑制剂组中年龄>60岁(RR=2.73,95%CI 1.84~4.05,P<0.001)、体质量指数≥31 kg/m^(2)(RR=2.73,95%CI 1.82~4.07,P<0.001)、治疗时间>52周(RR=2.73,95%CI 1.84~4.05,P<0.001)、使用卡格列净(RR=4.82,95%CI 1.70~13.64,P=0.003)、埃格列净(RR=4.10,95%CI 1.11~15.20,P=0.040)发生DKA风险均较对照组明显升高。结论成人T2DM患者应用SGLT-2抑制剂会增加DKA风险,且年龄越大、体质量指数越高、治疗时间越长发生DKA的风险就越高,另外DKA发生风险也与药物种类有关。

Role of the cation-chloride-cotransporters in the circadian system

The circadian system plays an immense role in controlling physiological processes in our body.The suprachiasmatic nucleus (SCN) supervises this system,regulating and harmonising the circadian rhythms in our body.Most neurons present in the SCN are GABAergic neurons.Although GABA is considered the main inhibitory neurotransmitter of the CNS,recent studies have shown that excitatory responses were recorded in this area.These responses are enabled by an increase in intracellular chloride ions[Cl;];levels.The chloride (Cl;) levels in GABAergic neurons are controlled by two solute carrier 12 (SLC12)cation-chloride-cotransporters (CCCs):Na^(+)/K^(+)/Cl^(-)co-transporter (NKCC1) and K^(+)/Cl^(-)cotransporter (KCC2),that respectively cause an influx and efflux of Cl^(-).Recent works have found altered expression and/or activity of either of these co-transporters in SCN neurons and have been associated with circadian rhythms.In this review,we summarize and discuss the role of CCCs in circadian rhythms,and highlight these recent advances which attest to CCC’s growing potential as strong research and therapeutic targets.

SGLT2i预防经皮冠状动脉介入术后支架内再狭窄的研究进展

支架内再狭窄是经皮冠状动脉介入治疗术后并发症发生的主要原因之一,也是介入领域的难题。钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)是近年来用于治疗糖尿病的新型口服降糖药,除了能降低血糖,还具有降低血压、改善血脂、减重等功效,具有心血管保护作用。近期研究发现,SGLT2i可以降低支架内再狭窄的发生,显著改善接受介入治疗的冠心病患者的预后。本文将对SGLT2i在预防经皮冠状动脉介入治疗术后再狭窄相关的临床研究及其作用机制做一综述,为改善冠心病患者的临床预后提供新思路。

钠-葡萄糖协同转运蛋白2抑制剂联合葶苈子治疗慢性心力衰竭合并肺部感染的临床疗效分析

目的探讨钠-葡萄糖协同转运蛋白2抑制剂联合葶苈子治疗对心力衰竭(心衰)合并肺部感染患者心功能、消化功能及肺功能的影响。方法选取秭归县中医院2017年8月至2019年3月收治的168例心衰合并肺部感染患者作为研究对象。根据治疗方法不同将患者分为观察组和对照组,每组84例。对照组接受钠-葡萄糖协同转运蛋白2抑制剂联合头孢他啶治疗,观察组在对照组基础上接受葶苈子治疗,共治疗30 d。比较两组治疗前后营养状态指标〔血清前白蛋白(PA)、白蛋白(ALB)、红细胞计数(RBC)、体质量指数(BMI)〕、免疫功能指标〔分化簇抗原(CD3、CD4、CD8)、免疫球蛋白(IgG、IgM)〕、血清炎症因子〔白细胞介素(IL-8、IL-10、IL-17)及肿瘤坏死因子(TNF-α)〕、肠道菌群(肠球菌、大肠埃希菌、乳杆菌、双歧杆菌、酵母菌、消化球菌)、心肺功能指标〔动脉血氧饱和度(PaO_(2))、动脉血二氧化碳分压(PaCO_(2))、心率、最大摄氧量(VO_(2)max)、最大运动负荷(Wmax)、最大氧脉搏、无氧阈值(AT)、第1秒用力呼气容积/用力肺活量比值(FEV1/FVC)、FEV1和每分最大通气量(MVV)〕。结果两组治疗后PA、ALB、RBC、BMI、CD3、CD4、CD8、IgG、IgM、乳杆菌、双歧杆菌、PaO_(2)、VO_(2)max、Wmax、最大氧脉搏、AT、FEV1/FVC、FEV1、MVV均较治疗前明显升高,IL-8、IL-17、TNF-α、肠球菌、大肠埃希菌、PaCO_(2)、心率水平均较治疗前明显降低,且观察组治疗后PA、ALB、RBC、BMI、CD3、IgG、IgM、IL-10、双歧杆菌、乳酸菌、PaO_(2)、VO_(2)max、Wmax、最大氧脉搏、AT、FEV1/FVC、FEV1、MVV水平均明显高于对照组〔PA(mg/L):259.69±20.73比217.69±20.73,ALB(g/L):41.46±4.58比36.56±3.73,RBC(×1012/L):4.52±0.24比4.21±0.31,BMI(kg/m^(2)):22.37±2.73比19.66±2.24,CD3:0.63±0.08比0.56±0.08,IgG(g/L):21.85±3.68比15.72±4.36,IgM(g/L):4.68±1.68比3.73±1.67,IL-10(ng/L):65.28±7.23比50.23±6.14,双歧杆菌(CFU/kg):83.5±8.6比78.5±8.3,乳酸菌(CFU/kg):62.1±6.5比53.5±6.0,PaO_(2)(mmHg,1 mmHg≈0.133 kPa):98.36±1.75比91.95±2.95,VO_(2)max(L/min):1.71±0.35比1.22±0.39,Wmax(W):127.49±19.54比97.49±15.37,最大氧脉搏(L/次):11.27±2.42比9.46±2.79,AT:(50.49±7.48)%比(41.35±6.67)%,FEV1/FVC:(75.68±5.86)%比(65.48±8.54)%,FEV1:(82.44±5.73)%比(73.57±7.75)%,MVV(L/min):74.86±10.64比64.63±9.68,均P<0.05〕,CD4、CD8、IL-8、IL-17、TNF-α、肠球菌、大肠埃希菌、PaCO_(2)、心率水平均显著低于对照组〔CD4:0.32±0.06比0.39±0.05,CD8:0.28±0.06比0.34±0.05,IL-8(ng/L):16.64±2.63比26.35±4.13,IL-17(ng/L):112.38±30.16比207.75±42.23,TNF-α(ng/L):45.27±10.23比61.26±14.29,肠球菌(CFU/kg):63.6±5.6比69.5±6.8,大肠埃希菌(CFU/kg):65.8±6.4比70.5±7.0,PaCO_(2)(mmHg):41.84±4.45比56.18±5.37,心率(次/min):75.96±11.57比91.75±12.68,均P<0.05〕。结论葶苈子联合钠-葡萄糖协同转运蛋白2抑制剂治疗心衰合并肺部感染,可有效改善患者心肺功能,降低炎症指标水平,提升患者的营养状态,纠正肠道菌群情况,对临床治疗有一定指导意义。