Network pharmacology-based therapeutic mechanism of Kuanxiong aerosol for angina pectoris.

ETHNOPHARMACOLOGICAL RELEVANCE: Kuanxiong aerosol has been reported to be an effective and safe clinical treatment for angina pectoris (AP). AIM OF THE STUDY: To explore the potential pharmacological mechanism of Kuanxiong aerosol by combined methods of network pharmacology prediction and experimental verification. MATERIALS AND METHODS: Networks of Kuanxiong aerosol-associated targets and AP-related genes were constructed through STRING database. Potential targets and pathway enrichment analysis related to the therapeutic efficacy of Kuanxiong aerosol were identified using Cytoscape and Database for Annotation, Visualization and Integrated Discovery (DAVID). To explore the mechanism of action of Kuanxiong aerosol, its in vitro effects on myocardial hypoxia, inflammatory cytokines, and oxidative injury, and its in vivo pharmacological effects on myocardial ischemia and cardiac fibrosis were studied in rat models. RESULTS: Network pharmacology analysis revealed that the potential targets mainly include the Fas ligand (FASLG), interleukin 4 (IL4), and catalase (CAT), which mediated the processes of apoptosis, and cellular responses to hypoxia, lipopolysaccharide (LPS), reactive oxygen species (ROS), and mechanical stimulus. Multiple pathways, such as the hypoxia-inducible factor 1 (HIF1) and tumor necrosis factor (TNF) pathways were found to be closely related to the pharmacological protective mechanism of Kuanxiong aerosol against AP. In addition, Kuanxiong aerosol suppressed the hypoxia, LPS, and hydrogen peroxide (H2O2)-induced injuries of H9c2 cardiomyocytes through the regulation of HIF1A, suppressed expression of IL6 and TNF, and antioxidant property. In the rat model of myocardial ischemia, Kuanxiong aerosol was found to lower the creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) levels, without altering the hemodynamic function. Kuanxiong aerosol was capable of attenuating cardiac fibrosis and improving cardiac function in a cardiac fibrosis rat model. CONCLUSIONS: This study revealed that the pharmacological mechanisms of Kuanxiong aerosol for AP therapy were related to anti-myocardial ischemia, anti-inflammation, and anti-oxidation via a non-hemodynamic manner, indicating that Kuanxiong aerosol is a preferable drug clinically for AP treatment due to its both preventive and protective effects.

Clinical Therapeutic Effects of Aspirin in Combination with Fufang Danshen Diwan, a Traditional Chinese Medicine Formula, on Coronary Heart Disease: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Coronary heart disease is characterized by vascular stenosis or occlusion resulting in myocardial ischemia, hypoxia and necrosis. In China, the combination of aspirin and Fufang Danshen Diwan (FDD), a traditional Chinese medicine formula, has been suggested in the treatment of coronary heart disease. There have been several studies comparing the effectiveness of aspirin alone and in combination with FDD to treat coronary artery disease; however, it remains unclear whether combined aspirin therapy is superior. This study was thus designed to clarify this issue through a systematic review and meta-analysis. METHODS: Databases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) database, Wanfang Data and VIP Information were searched. Papers were reviewed systematically by two researchers and analyzed using Cochrane software Revman 5.1. RESULTS: Fourteen randomized controlled trials enrolling 1367 subjects were included. Meta-analyses revealed that aspirin in combination with FDD was significantly more effective at alleviating angina pectoris and improving electrocardiogram (ECG) results relative to aspirin therapy alone, reflected by the summary effects for the clinical markedly effective (OR = 2.45; 95% CI 1.95-3.08) and the total effective (OR = 3.92; 95% CI 2.87-5.36) rates. In addition, combined aspirin and FDD was significantly more efficacious than aspirin monotherapy at improving blood lipid levels, as indicated by the following outcomes: 1) reduction of TC level (SMD -1.12; 95% CI -1.49 to -0.76); 2) reduction of TG level (SMD -0.94; 95% CI -1.15 to -0.74); 3) reduction of LDL level (SMD -0.68; 95% CI -0.88 to -0.48); and 4) improvement of HDL level (SMD 0.52; 95% CI 0.04 to 0.99 ). No serious adverse events were reported in any of the included trials. CONCLUSION: The present meta-analysis demonstrated that aspirin in combination with FDD was more effective than aspirin alone for treating coronary heart disease. More full-scale randomized clinical trials with reliable designs are recommended to further evaluate the clinical benefits and long-term effectiveness of FDD for the treatment of coronary heart disease.

[Myocardial cytoprotectors, a reserve therapeutic modality for patients with stable angina of effort].

The study included 1418 patients with FC I-IV stable angina of effort (42.4% men and 57.6% women, mean age 74.6 +/- 1.2 years). The possibility to supplement standard therapy with myocardial cytoprotectors (trimetasidin, mexidol, qudesan) was estimated in 4 groups of patients from the severity of pain syndrome, chronic cardiac insufficiency, and heart rhythm disturbances.

Multivessel coronary artery spasm refractory to intensive medical treatment.

This case report describes multivessel coronary artery spasm refractory to oral nifedipine, intravenous isosorbide dinitrate, diltiazem and nicorandil, and intracoronary nitroglycerin. Intracoronary administration of nicorandil only transiently relieved coronary artery spasm. Prednisolone was effective in preventing coronary artery spasm.

Effect of nifedipine on C-reactive protein levels in the coronary sinus and on coronary blood flow in response to acetylcholine in patients with stable angina pectoris having percutaneous coronary intervention.

The effects of nifedipine on inflammation and endothelial function in the coronary circulation were studied in patients who had angina pectoris (n = 17). Long-term treatment with nifedipine (nifedipine CR, 20 mg/day for 4 months) decreased levels of C-reactive protein in the coronary sinus (from 0.35 +/- 0.09 mg/dl to 0.07 +/- 0.01 mg/dl, mean +/- SEM, p <0.05) and enhanced acetylcholine-induced increases in coronary blood flow. Thus, nifedipine is effective in decreasing inflammation and incresing endothelial function in the coronary circulation.

[Clinico-functional efficacy of medicinal and photon stabilization of cell membrane in patients with angina pectoris]. / Kliniko-funktsional'naia éffektivnost' medikamentoznoi i kvantovoi stabilizatsii kletochnoi membrany u bol'nykh stenokardiei.

Modification of erythrocytic membrane and the trend in clinicofunctional indices were studied in 90 patients with angina of effort (FC I-IV) in the course of treatment with a combination of membranoprotective drugs (group 1), magneto-laser radiation (group 2) and imitation of laser radiation (group 3). In patients of groups 1 and 2 the treatment resulted in stabilization of cell membrane accompanied with a hypotensive effect and increased exercise tolerance due to more effective cardiac performance.

The reported clinical utility of taurine in ischemic disorders may reflect a down-regulation of neutrophil activation and adhesion.

The first publications regarding clinical use of taurine were Italian reports claiming therapeutic efficacy in angina, intermittent claudication and symptomatic cerebral arteriosclerosis. A down-regulation of neutrophil activation and endothelial adhesion might plausibly account for these observations. Endothelial platelet-activating factor (PAF) is a crucial stimulus to neutrophil adhesion and activation, whereas endothelial nitric oxide (NO) suppresses PAF production and acts in various other ways to antagonize binding and activation of neutrophils. Hypochlorous acid (HOCl), a neutrophil product which avidly oxidizes many sulfhydryl-dependent proteins, can be expected to inhibit NO synthase while up-regulating PAF generation; thus, a vicious circle can be postulated whereby HOCl released by marginating neutrophils acts on capillary or venular endothelium to promote further neutrophil adhesion and activation. Taurine is the natural detoxicant of HOCl, and thus has the potential to intervene in this vicious circle, promoting a less adhesive endothelium and restraining excessive neutrophil activation. Agents which inhibit the action of PAF on neutrophils, such as ginkgolides and pentoxifylline, have documented utility in ischemic disorders and presumably would complement the efficacy of taurine in this regard. Fish oil, which inhibits endothelial expression of various adhesion factors and probably PAF as well, and which suppresses neutrophil leukotriene production, may likewise be useful in ischemia. These agents may additionally constitute a non-toxic strategy for treating inflammatory disorders in which activated neutrophils play a prominent pathogenic role. Double-blind studies to confirm the efficacy of taurine in symptomatic chronic ischemia are needed.

[Clinical study on protective effect of xinmaitong capsule on damage of vascular endothelial cells].

OBJECTIVE: To assess the effect of Xinmaitong (XMT) capsule in treating coronary heart disease (CHD). METHODS: Thirty-eight patients of coronary heart disease with myocardial ischemia were divided randomly into XMT group (20 cases) and control group (18 cases). Conventional western medical therapy was given to both groups and the XMT group received additional XMT treatment. The changes of endothelin (ET) and calcitonin gene-related peptide (CGRP) levels, ST segment of ECG and clinical symptoms after treatment in all the patients were observed. Data of 14 healthy persons were taken as normal control. RESULTS: The ET level of all patients was significantly higher than that of the normal control (P < 0.001), and level of CGRP in patients was not different from normal control significantly (P > 0.05). After treatment, results showed that: (1) The ET levels and the scores of clinical symptoms of both groups decreased significantly (P < 0.01), and ST segment elevated markedly (P < 0.01) as compared with before treatment, and the changes revealed more evident in XMT group in comparison with those of the control group (P < 0.05-P < 0.01). (2) The level of CGRP was significantly increased in XMT group (P < 0.01) while unchanged in the control group (P > 0.05). CONCLUSIONS: There is severe damage of vascular endothelial cells in CHD patients. XMT could not only reduce significantly the plasma ET content, but also enhance markedly the production and release of CGRP, so it has a good anti-ischemic effect, which may be closely related with its action on improving the function of vascular endothelial cells and regulating metabolism of ET and CGRP.

Percutaneous transluminal coronary angioplasty versus medical therapy for stable angina pectoris: outcomes for patients with double-vessel versus single-vessel coronary artery disease in a Veterans Affairs Cooperative randomized trial. Veterans Affairs ACME InvestigatorS.

OBJECTIVES: This study sought to assess outcomes of men with double-vessel coronary artery disease randomly assigned to treatment by percutaneous transluminal coronary angioplasty (PTCA) or medical therapy, compared with previously reported outcomes for men with single-vessel disease. BACKGROUND: We previously reported that PTCA provides better symptom relief and treadmill performance than medical therapy for men with stable angina pectoris due to single-vessel disease. Whether this advantage applies to patients with double-vessel disease is unknown. METHODS: Male patients (n = 328) with stable angina pectoris and ischemia on treadmill testing were randomly assigned to PTCA or medical therapy; 101 patients had double-vessel disease, and 227 had single-vessel disease. Symptoms, treadmill performance, quality of life score, coronary stenosis and myocardial perfusion were compared at baseline and at 6 months. Patients were followed up for up to 6 years and underwent additional treadmill testing 2 to 3 years after randomization. RESULTS: PTCA-treated and medically treated patients with double-vessel disease experienced comparable improvement in exercise duration (+1.2 vs. +1.3 min, respectively, p = 0.89), freedom from angina (53% and 36%, respectively, p = 0.09) and improvement of overall quality of life score (+1.3 vs. +4.4, respectively, p = 0.32) at 6 months compared with baseline. This contrasts with greater advantages favoring PTCA by these criteria in patients with single-vessel disease (p = 0.0001 to 0.02). Trends present at 6 months persisted at late follow-up. Patients undergoing double-vessel dilation had less complete initial revascularization (45% vs. 83%) and greater average stenosis of worst lesions at 6 months (74% vs. 56%). Likewise, patients with double-vessel disease showed less improved myocardial perfusion imaging (59% vs. 75%). CONCLUSIONS: PTCA is beneficial in male patients with double-vessel disease; however, we cannot demonstrate the same advantage over medical therapy seen in similar patients with single-vessel disease. Less complete revascularization and greater restenosis for patients having multiple dilations would account for these findings. Alternatively, a type 2 error might be operative. Technical advances since completion of this trial might improve these outcomes. These findings warrant further investigation in a larger trial.

[Changes in the vascular wall and ischemic damages to the myocardium in reversible episodes of heart muscle ischemia]. / Izmeneniia sosudistoi stenki i ishemicheskie povrezhdeniia miokarda pri obratimykh épizodakh ishemii serdechnoi myshtsy.

When no anaesthetic is used, even 3-5 short-term disturbances of the myocardium supply with blood (during a few days) are enough for its initial necrosis and for damage of its vascular bed. In acute experiments on rats rutin discovers the ability to resist such damages, but on the chronic model of stenocardia in dogs its therapeutic effect can be found only under conditions of limitation of the ischemic effect by purposefully chosen complex medicinal therapy.

[Comparison of the effects of nifedipine and diltiazem in patients with stable angina pectoris of various severity and pathomorphology of the coronary arteries]. / Srovnání úcinku nifedipinu a diltiazemu u nemocných se stabilní anginou pectoris a ruznou tízí a patomorfologií postizení koronárních tepen.

In a double blind 7-week randomized study the authors compared in 29 patients with stable angina the action of placebo, nifedipine and diltiazem. Nifedipine was administered in amounts of 60 mg/day for three weeks, diltiazem 270 mg/day also for three weeks. Nifedipine and diltiazem exerted a significant antianginous action in patients with occluded but collateralized coronary arteries (group A), as well as in patients without collaterals (group B). In both these groups diltiazem improved the load tolerance significantly more than nifedipine. Nifedipine and diltiazem were useful also in patients with mild (group E), medium (group D) and severe (group C) affections of the coronary arteries. Groups C and E differed significantly as to the different effect of nifedipine and diltiazem on load S-T depressions (in group C diltiazem was significantly more effective, in group E nifedipine was insignificantly better), and it was not possible to explain these differences by a different effect on Robinson's index. The authors conclude that neither nifedipine nor diltiazem led in the amounts used to the "steal phenomenon" with clinical impact. In patients with mild affections of the coronary arteries their antiischaemic and antianginous action was similar, in patients with severe affection of the coronary arteries diltiazem was more effective.