Shenfu Administration Improves Cardiac Fibrosis in Rats With Myocardial Ischemia-Reperfusion Through Adenosine A2a Receptor Activation.

OBJECTIVE: Shenfu injection (SFI) is commonly used for cardiac dysfunction in China. Adenosine receptors have been reported to exert anti-fibrosis effects. The intent of this study was to evaluate that SFI attenuates cardiac fibrosis through activating of adenosine A2a receptor (A2aR) in rats with myocardial ischemia-reperfusion (MI/R). METHODS: Sprague Dawley male rats were randomly divided into five groups, nine rats in each group. Injections in all rat groups were carried out prior to reperfusion, and in the sham and MI/R groups, only vehicle was injected. Injections in the remaining group were as follows: 5 mL/kg in the SFI group; 15 mg/kg nicorandil in the A2R agonist group; and 5 mL/kg SFI plus 5 mg/kg MSX-3 in the SFI + A2aR antagonist group. Changes in cyclic adenosine monophosphate (cAMP) and the development of myocardial infarction and cardiac fibrosis were documented among the groups. Additionally, the levels of A2aR, collagen Ⅰ, collagen Ⅲ, fibronectin, and matrix metalloproteinase-9 (MMP-9) were measured. RESULTS: Following injection with SFI or nicorandil, the cAMP concentration, infarct area, and cardiac fibrosis induced by MI/R injury were significantly decreased (p < 0.05). Additionally, the levels of collagen Ⅰ, collagen Ⅲ, fibronectin, and MMP-9 were clearly suppressed by SFI or nicorandil when compared with the MI/R group (p<0.01). However, the protective effects of SFI were counteracted by MSX-3. A negative correlation between A2aR and collagen I and collagen III was found (p = 0.00). CONCLUSION: SFI activated the A2aR to reduce myocardial fibrosis caused by MI/R injury, which provided an underlying mechanism of action of SFI.

Clinical outcomes of nicorandil administration in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Primary percutaneous coronary intervention is the treatment of choice in ST-segment elevation myocardial infarction and no-reflow phenomenon is still an unsolved problem. METHODS: We searched PubMed, EmBase, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials. The primary endpoint was the incidence of major adverse cardiac events and the secondary endpoint was the incidences of no-reflow phenomenon and complete resolution of ST-segment elevation. RESULTS: Eighteen randomized controlled trials were enrolled. Nicorandil significantly reduced the incidence of no-reflow phenomenon (OR, 0.46; 95% CI, 0.36-0.59; P < 0.001; I2 = 0%) and major adverse cardiac events (OR, 0.42; 95% CI, 0.27-0.64; P < 0.001; I2 = 52%). For every single outcome of major adverse cardiac events, only heart failure and ventricular arrhythmia were significantly improved with no heterogeneity (OR, 0.36; 95% CI, 0.23-0.57, P < 0.001; OR, 0.43; 95% CI, 0.31-0.60, P < 0.001 respectively). A combination of intracoronary and intravenous nicorandil administration significantly reduced the incidence of major adverse cardiac events with no heterogeneity (OR, 0.24; 95% CI, 0.13-0.43, P < 0.001; I2 = 0%), while a single intravenous administration could not (OR, 0.66; 95% CI, 0.40-1.06, P = 0.09; I2 = 52%). CONCLUSIONS: Nicorandil can significantly improve no-reflow phenomenon and major adverse cardiac events in patients undergoing primary percutaneous coronary intervention. The beneficial effects on major adverse cardiac events might be driven by the improvements of heart failure and ventricular arrhythmia. A combination of intracoronary and intravenous administration might be an optimal usage of nicorandil.

Clinical Efficacy of Intracoronary Papaverine After Nicorandil Administration for Safe and Optimal Fractional Flow Reserve Measurement.

Fractional flow reserve (FFR) is considered the standard for assessment of the physiological significance of coronary artery stenosis. Intracoronary papaverine (PAP) is the most potent vasodilator used for the achievement of maximal hyperemia. However, its use can provoke ventricular tachycardia (VT) due to excessive QT prolongation. We evaluated the clinical efficacy and safety of the administration of PAP after nicorandil (NIC), a potassium channel opener that prevents VT, for optimal FFR measurement.A total of 127 patients with 178 stenoses were enrolled. The FFR values were measured using NIC (NIC-FFR) and PAP (PAP-FFR). We administered PAP following NIC (NIC-PAP). Changes in the FFR and electrogram parameters (baseline versus NIC versus PAP) were assessed and the incidence of arrhythmias after PAP was evaluated. In addition, we analyzed another 41 patients with 51 stenoses by assessing the FFR using PAP before NIC (PAP-NIC). After propensity score matching, the electrogram parameters between 2 groups were compared.The mean PAP-FFR was significantly lower than the mean NIC-FFR (0.82 ± 0.11 versus 0.81 ± 0.11, P < 0.05). The mean baseline-QTc, NIC-QTc, and PAP-QTc values were 425 ± 37 ms1/2, 424 ± 41 ms1/2, and 483 ± 54 ms1/2, respectively. VT occurred in only 1 patient (0.6%). Although PAP induced QTc prolongation (P < 0.05), the PAP-QTc duration was significantly shorter in NIC-PAP compared to PAP-NIC (P < 0.05).The administration of PAP with NIC may induce sufficient hyperemia and prevent fatal arrhythmia through reductions in the PAP-induced QTc prolongation during FFR measurement.

Mitochondrial Quality Control in Cerebral Ischemia-Reperfusion Injury.

Ischemic stroke is one of the leading causes of death and also a major cause of adult disability worldwide. Revascularization via reperfusion therapy is currently a standard clinical procedure for patients with ischemic stroke. Although the restoration of blood flow (reperfusion) is critical for the salvage of ischemic tissue, reperfusion can also, paradoxically, exacerbate neuronal damage through a series of cellular alterations. Among the various theories postulated for ischemia/reperfusion (I/R) injury, including the burst generation of reactive oxygen species (ROS), activation of autophagy, and release of apoptotic factors, mitochondrial dysfunction has been proposed to play an essential role in mediating these pathophysiological processes. Therefore, strict regulation of the quality and quantity of mitochondria via mitochondrial quality control is of great importance to avoid the pathological effects of impaired mitochondria on neurons. Furthermore, timely elimination of dysfunctional mitochondria via mitophagy is also crucial to maintain a healthy mitochondrial network, whereas intensive or excessive mitophagy could exacerbate cerebral I/R injury. This review will provide a comprehensive overview of the effect of mitochondrial quality control on cerebral I/R injury and introduce recent advances in the understanding of the possible signaling pathways of mitophagy and potential factors responsible for the double-edged roles of mitophagy in the pathological processes of cerebral I/R injury.

Cardiovascular magnetic resonance image analysis and mechanism study for the changes after treatments for primary microvascular angina pectoris.

ABSTRACT: Most cases of primary microvascular angina pectoris (PMVA) are diagnosed clinically, but the etiology and pathological mechanisms are unknown. The effect of routine clinical medications is minimal, and PMVA can progress to serious cardiovascular events. To improve the diagnosis and effective treatment of this disease, this study was designed to diagnose PMVA via cardiovascular magnetic resonance (CMR) and the coronary angiography thrombolysis in myocardial infarction (TIMI) blood flow grade, as well as to analyze vascular endothelial function to elucidate the pathogenesis of PMVA and compare the effects of routine clinical medications.The present randomized controlled trial including a parallel control group will be conducted on 63 PMVA patients in our cardiovascular department. The patients will be selected and randomly divided into the control, diltiazem, and nicorandil groups. The control group will be administered routine drug treatments (aspirin, atorvastatin, betaloc ZOK, perindopril, and isosorbidemononitrate sustained-release tablets). The diltiazem group will be additionally treated with 90 mg qd diltiazem sustained-release capsules. The nicorandil group was additionally given 5 mg tid nicorandil tablets. Coronary angiography will be performed before treatment, the severity and frequency of chest pain will be evaluated before and after 9 months of treatment, and homocysteine and von Willebrand factor levels will be measured. Electrocardiography, echocardiography, dynamic electrocardiography, a treadmill exercise test, and CMR will be performed. Sex, age, body mass index, complications, smoking, and family history will also be recorded. The SPSS19.0 statistical software package will be used to analyze the data. The measurements will be expressed as the mean ±â€Šstandard deviation. Measurement data will be compared between the groups using Student's t-test. A relative number description will be used for the counting data, and the chi-squaretest will be used to compare the groups. A multivariate logistic regression analysis will be performed A P-value < .05 will be considered significant.The direct indices (CMR and coronary angiographic TIMI blood flow grade) may improve after adding diltiazem or nicorandil during routine drug treatments (such as aspirin, statins, and nitrates) in PMVA patients, and indirect indices (homocysteine and von Willebrand factor levels) may be reduced. TRIAL REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org.cn/showprojen.aspx?proj=41894), No. CHiCTR1900025319, Registered on August 23, 2019; pre initiation.

Impact of administration of nicorandil prior to percutaneous coronary intervention in treatment of acute myocardial infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: In order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the efficacy and safety of nicorandil prior to percutaneous coronary intervention in acute myocardial infarction (AMI) patients. METHODS: This systematic review and meta-analysis will be performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently will search randomized controlled trials or observational studies about the treatment of nicorandil on AMI patients. Retrieved databases include Web of Science, ClinicalTrials.gov, Pubmed, Embase, and Cochrane Library. And retrieval time is limited from inception to June 2021. Key words are nicorandil, myocardial infarction, or similar expansion words without publication limitation. Biomechanical studies, in vitro studies, review articles, techniques, case reports, letters to the editor, and editorials are excluded. RESULTS: The results of our review will be reported strictly following the PRISMA criteria and the review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/UEPKB.

Prophylactically injection of Nicorandil to reduce no-reflow phenomenon during PCI in acute STEMI patients: Protocol of a double-blinded, randomized, placebo-controlled trial.

INTRODUCTION: An acute ST-elevation myocardial infarction (STEMI) is a very serious type of heart attack and a profoundly life-threatening medical emergency, and percutaneous coronary intervention (PCI) is the preferred strategy. However, in patients undergoing primary PCI, 30% to 40% may suffer the no-reflow phenomenon (NRP), and it could expand the myocardial infarction area and accompanied with high rehospitalization rate and fatality rate. In this study, we try to conduct a double blinded, randomized, placebo-controlled trial to observe whether the prophylactically intracoronary administration of Nicorandil could reduce the occurrence of NRP in STEMI patients undergoing PCI. METHODS: Simple randomization in a 1:1 ratio will be made in blocks of variable size according to a random numbers generated by Excel 2010 to divide the patients to treatment group (Nicorandil) and control group (Saline). The outcomes are the occurrence of NRP, levels of interleukin-6 and HS-CRP, cTnT, and CK-MB before, and every 4 hours following PCI, and major adverse cardiovascular events at day 30. SPSS 23.0 (IBM, Chicago, IL) will be used, and P-value < .05 will be considered statistically significant. CONCLUSIONS: The findings will determine the efficacy of prophylactically intracoronary administration of Nicorandil to reduce the occurrence of NRP during PCI in acute STEMI patients. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/QPF3V.

Myocardial protective effect of intracoronary administration of nicorandil and alprostadil via targeted perfusion microcatheter in patients undergoing elective percutaneous coronary intervention: A randomized controlled trial.

BACKGROUND: The aim of the study was to evaluate the efficacy of nicorandil and alprostadil on myocardial protection in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: In this prospective, single-blinded, randomized controlled study, 90 consecutive patients scheduled for elective PCI for de novo coronary lesions were assigned to the nicorandil, alprostadil, and nitroglycerin groups in a 1:1:1 ratio. Drugs were administered intracoronary via a targeted perfusion microcatheter. The primary endpoint was the thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC). Additionally, the corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG), and incidence of periprocedural myocardial injury (PMI) were assessed. RESULTS: Both nicorandil and alprostadil were significantly effective in reducing TMPFC (114.6 ±â€Š33.7 vs 93.4 ±â€Š30.9, P = .016; 114.3 ±â€Š34.3 vs 94.7 ±â€Š33.3, P = .029, respectively). Similar findings were observed in the improvement of cTFC (20.3 ±â€Š10.5 vs 13.5 ±â€Š5.0, P = .003; 20.2 ±â€Š7.4 vs 15.2 ±â€Š5.2, P = .003, respectively) and percentage of TMPG 3 (100% vs 82.8%, P = .052; 83.3% vs 96.7%, P = .196, respectively); whereas, nitroglycerin produced a limited effect on TMPFC (114.4 ±â€Š30.9 vs 112.1 ±â€Š31.9, P = .739), cTFC (19.4 ±â€Š7.2 vs 19.3 ±â€Š7.2, P = .936), and percentage of TMPG 3 (86.7% vs 86.7%, P = 1.000). No significant difference was found in the incidence of PMI (16.7% vs 16.0% vs 27.6%, P = .537), though it was comparatively lower in the nicorandil and alprostadil groups. Furthermore, the intracoronary administration of nicorandil and alprostadil had a mild effect on blood pressure and heart rate. CONCLUSIONS: The intracoronary administration of nicorandil and alprostadil via a targeted perfusion microcatheter was more effective in improving myocardial perfusion in patients undergoing elective PCI than nitroglycerin.

Achieving Optimal Medical Therapy: Insights From the ORBITA Trial.

Background In stable coronary artery disease, medications are used for 2 purposes: cardiovascular risk reduction and symptom improvement. In clinical trials and clinical practice, medication use is often not optimal. The ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial was the first placebo-controlled trial of percutaneous coronary intervention. A key component of the ORBITA trial design was the inclusion of a medical optimization phase, aimed at ensuring that all patients were treated with guideline-directed truly optimal medical therapy. In this study, we report the medical therapy that was achieved. Methods and Results After enrollment into the ORBITA trial, all 200 patients entered a 6-week period of intensive medical therapy optimization, with initiation and uptitration of risk reduction and antianginal therapy. At the prerandomization stage, the median number of antianginals established was 3 (interquartile range, 2-4). A total of 195 patients (97.5%) reached the prespecified target of ≥2 antianginals; 136 (68.0%) did not stop any antianginals because of adverse effects, and the median number of antianginals stopped for adverse effects per patient was 0 (interquartile range, 0-1). Amlodipine and bisoprolol were well tolerated (stopped for adverse effects in 4/175 [2.3%] and 9/167 [5.4%], respectively). Ranolazine and ivabradine were also well tolerated (stopped for adverse effects in 1/20 [5.0%] and 1/18 [5.6%], respectively). Isosorbide mononitrate and nicorandil were stopped for adverse effects in 36 of 172 (20.9%) and 32 of 141 (22.7%) of patients, respectively. Statins were well tolerated and taken by 191 of 200 (95.5%) patients. Conclusions In the 12-week ORBITA trial period, medical therapy was successfully optimized and well tolerated, with few drug adverse effects leading to therapy cessation. Truly optimal medical therapy can be achieved in clinical trials, and translating this into longer-term clinical practice should be a focus of future study. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02062593.

The effectiveness and safety of nicorandil in the treatment of patients with microvascular angina: A protocol for systematic review and meta-analysis.

BACKGROUND: Microvascular angina has become a clinical and frequent cardiovascular disease in recent years, which is complicated and there is no clear treatment. Today, Western medicine still deals with microvascular angina with standardized treatment based on the stable angina. Firstly, it is to control the risk factors of atherosclerosis, and the second is to reduce the oxygen consumption of the patient's heart muscle. In the previous randomized controlled clinical trials, it has shown that nicorandil can improve the symptoms of angina for the treatment of microvascular angina, but there is a lack of high-quality randomized controlled trials on the clinical effectiveness and safety of nicorandil in the treatment of microvascular angina, and the lack of evaluation of its effectiveness and safety. Therefore, this paper aims to understand whether nicorandil can further improve the prognosis of patients with microvascular angina and the safety of the drug through the method of systematic evaluation. METHODS: Retrieval of relevant network electronic databases by computer: SinoMed, CNKI, WanFang Data, VIP, PubMed, EMbase and The Cochrane Library, the retrieval time is from the establishment of each database to December 2017, to collect randomized controlled studies of nicorandil in the treatment of microvascular angina. At the same time, it is supplemented by manual search of the included literature references, as far as possible to increase the included literature imformation. Two researchers independently browse the topics and abstracts, and select, find, read the full text of the relevant literature, and screen the literature according to the criteria for inclusion and exclusion established in advance, then extract the data, and cross-check, and resolve the differences through multi-person discussion. Data analysis of collected information is performed by using RevMan 5.3 software. RESULTS: The data of the included literature are statistically analyzed by meta-analysis, and the key outcome indicators are used to determine whether nicorandil can further improve the prognosis of patients with microvascular angina and the safety of the drug. CONCLUSION: Through the method of evidence-based medicine, this study finds the existing problems and defects in the current research, which will provide high-quality evidence-based medical evidence for nicorandil's treatment of microvascular angina, and it help the clinical treatment and further research. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/DSQG9.

Diagnostic utility and safety of intracoronary nicorandil as a hyperemic agent for the measurement of fractional flow reserve.

We investigated the diagnostic utility and safety of intracoronary bolus administration of nicorandil compared with intravenous administration of adenosine for evaluating FFR in patients with intermediate (40-70%) coronary stenosis. The FFR values obtained with nicorandil and adenosine showed linear relationship. This correlation is statistically significant with regression coefficient of 0.932 (R2 = 0.834, p < 0.001). The side effects such as bronchospasm, hypotension, and bradycardia were significantly higher after administration of adenosine compared to nicorandil (20% vs. 1.66%, p = 0.001). Intracoronary use of nicorandil seems to be promising in offering the advantages of lesser side effects, similar efficacy, and lesser cost as compared to adenosine.

Efficacy and Safety of Nicorandil in Preventing Contrast-Induced Nephropathy after Elective Percutaneous Coronary Intervention: A Pooled Analysis of 1229 Patients.

BACKGROUND: Nicorandil in reducing contrast-induced nephropathy (CIN) following elective percutaneous coronary intervention (PCI) is an inconsistent practice. This article aims to evaluate the efficacy and safety of nicorandil in preventing CIN after elective PCI. METHODS: This is a pooled analysis of patients treated with elective PCI. The primary outcome was the incidence of CIN. The secondary outcomes were major adverse events, including mortality, heart failure, recurrent myocardial infarction, stroke, and renal replacement therapy. RESULTS: A total of 1229 patients were recruited in our study. With statistical significance, nicorandil lowered the risk of CIN (odds ratio = 0.26; 95% confidence interval = 0.16-0.44; P < 0.00001; I 2 = 0%) in patients who underwent elective PCI. In addition, no significant differences were observed in the incidence of mortality, heart failure, recurrent myocardial infarction, stroke, and renal replacement therapy between the two groups (P > 0.05). CONCLUSIONS: Our article indicated that nicorandil could prevent CIN without increasing the major adverse events. Furthermore, sufficiently powered and randomized clinical studies are still needed in order to determine the role of nicorandil in preventing CIN after elective PCI.

Primary angioplasty after distal intracoronary infusion of nicorandil solution mixed with contrast media.

A 50-year-old woman presented with history of intermittent angina for 2 days and signs of extensive anterior wall myocardial infarction. An urgent coronary angiogram showed a large proximally occluded left anterior descending (LAD) artery with no distal vessel opacification. After one attempt of thrombus aspiration, there was no improvement in Thrombolysis in Myocardial Infarction (TIMI) flow. The aspiration catheter was then parked in the distal vessel beyond the thrombotic lesion and 2 mg of intravenous nicorandil drug mixed with 10 mL of 50% dilute iodinated contrast media was infused slowly. A comparison was made to proximal vessel angiogram and the angioplasty procedure was then completed with a right size stent, restoring TIMI 3 flow in the LAD. This method minimises clot manipulations by avoiding repeated balloon predilatations or thrombus aspiration attempts and thus prevents the occurrence of no-reflow in lesions with large thrombus burden.

Genetic Risk of Diverticular Disease Predicts Early Stoppage of Nicorandil.

Gastrointestinal fistulation has been widely reported as an adverse effect of nicorandil therapy in Europe. People who have underlying diverticular disease are most at risk of this side effect. In Western countries, diverticular disease is highly prevalent and can be clinically silent. This study aimed to identify diverticular disease genetic risk scores (GRSs) associated with early nicorandil stoppage, a surrogate marker for drug intolerance. A case-control study was carried out on 1,077 patients from the Genetics of Diabetes Audit and Research Tayside Scotland (GoDARTS) database. Cases were defined as having < 9 nicorandil prescriptions with no identifiable reason for stopping (n = 230). Controls had either ≥ 9 prescriptions, treatment continuation to death/study end or stoppage post-myocardial infarction. Two diverticular GRSs were created and used in logistic regression models. Isosorbide mononitrate was used as a control analysis. Patients with a raised diverticular GRS, based on 23 replicable loci, had increased risk of stopping nicorandil therapy early (univariate (odds ratio (OR) 2.26; P = 0.04], multivariate (OR 3.96; P = 0.01)). Similar trends were noted when using the full 42 variant diverticular score but statistical significance was not reached. The isosorbide control analysis did not reach statistical significance. Our analysis demonstrates a novel positive association between a raised diverticular GRS and early stoppage of nicorandil therapy.

Effect of nicorandil administration on cardiac burden and cardio-ankle vascular index after coronary intervention.

Myocardial injury is a problem associated with percutaneous coronary intervention (PCI). This study aimed to clarify the role of nicorandil administration in preventing myocardial injury. This study included patients with stable angina who underwent PCI from November 2013 to June 2016. Of 58 consecutive patients, the first 20 patients received only saline infusion after PCI (control group); the other 38 patients received a continuous intravenous infusion of nicorandil and saline after PCI (nicorandil group). Troponin I and brain natriuretic peptide (BNP) levels were measured. Vascular parameters, such as blood pressure (BP), cardiac output, cardio-ankle vascular index (CAVI), and estimated systemic vascular resistance (eSVR), were measured. Troponin I of both groups increased 12 h after PCI. Changes in BNP levels between immediately after PCI and 12 h after PCI were significantly higher in the control than in the nicorandil group (10.8 ± 44.2 vs. - 2.6 ± 14.6 pg/ml, p = 0.04). In the nicorandil group, BP, eSVR, and CAVI decreased significantly at 12 h after PCI compared with those immediately after PCI (p < 0.0001), whereas no change was observed in the control group. In a single linear analysis, the change in BP (r = 0.36, p < 0.01) and nicorandil administration (r = - 0.47, p < 0.001) was significantly correlated with the change in CAVI, multiple regression analysis revealed that the changes in CO and eSVR were significant contributing factors for the changes in CAVI. PCI could result in myocardial injury and/or cardiac burden in patients with stable angina. Nicorandil administration after PCI may be effective in relieving the burden by decreasing arterial stiffness (CAVI).

Influence of caffeine intake on intravenous adenosine-induced fractional flow reserve.

BACKGROUND: This study evaluated whether caffeine abstention is required before fractional flow reserve (FFR) measurement by intravenous adenosine triphosphate (ATP) administration in Japanese patients. METHODS: This study was a subanalysis of a previously published study and a total of 208 intermediate lesions that underwent FFR measurements were enrolled for this analysis. Hyperemia was induced by continuous intravenous ATP infusion at 150 µg/kg/min (IVATP150) and 210 µg/kg/min (IVATP210), and by intracoronary administration of nicorandil 2 mg (ICNIC2mg) as a reference standard. RESULTS: The degree of change in the FFR value after ICNIC2mg and IVATP210 was similar between the caffeine and non-caffeine groups (0.00 ± 0.02 vs. 0.01 ± 0.02). In patients who consumed caffeine before the FFR measurement, the degree of FFR change was independent of the time interval (<12 h, 12-24 h, and 24-48 h) between caffeine intake and catheterization both after IVATP150 and ICNIC2mg and after IVATP210 and ICNIC2mg. CONCLUSION: When compared with the FFR value after ICNIC2mg, the degree of change in the FFR value after IVATP210 were similar regardless of caffeine intake. Strict caffeine abstention before intravenous ATP-induced FFR measurement may not be required in clinical practice.

Exogenous NO Therapy for the Treatment and Prevention of Atherosclerosis.

Amyl nitrite was introduced in 1867 as the first molecule of a new class of agents for the treatment of angina pectoris. In the following 150 years, the nitric oxide pathway has been the subject of a number of pharmacological approaches, particularly since when this elusive mediator was identified as one of the most important modulators of vascular homeostasis beyond vasomotion, including platelet function, inflammation, and atherogenesis. While having potent antianginal and antiischemic properties, however, nitric oxide donors are also not devoid of side effects, including the induction of tolerance, and, as shown in the last decade, of oxidative stress and endothelial dysfunction. In turn, endothelial dysfunction is itself felt to be involved in all stages of atherogenesis, from the development of fatty streaks to plaque rupture and thrombosis. In the present review, we summarize the agents that act on the nitric oxide pathway, with a particular focus on their potentially beneficial antiatherosclerotic and unwanted pro-atherosclerotic effects.

Intracoronary application of nicorandil regulates the inflammatory response induced by percutaneous coronary intervention.

Intracoronary application of nicorandil can effectively reduce the myocardial no-reflow (MNR) after percutaneous coronary intervention (PCI). We sought to investigate the mechanisms of nicorandil in preventing MNR, besides that of dilating the coronary microvasculature. A total of 60 patients undergoing PCI were enrolled and randomly divided into a nicorandil group and a control group. Before PCI, 2 mg of nicorandil or an equal volume of normal saline was injected into the coronary artery. Blood samples were collected before, 24 hours and 1 week after PCI and inflammatory cytokines were tested. In the control group, the expression of pro-inflammatory cytokines was significantly increased, while the anti-inflammatory cytokines were decreased 24 hours after PCI. In contrast, these changes were reversed in the nicorandil group, indicating that nicorandil regulated the inflammatory response induced by PCI. Then, proteomic analysis was performed to further elucidate the potential mechanisms. A total of 53 differentially expressed proteins (DEPs) were found 24 hours after PCI in the control group, and the changes of these relevant genes were reversed in the nicorandil group. These DEPs were significantly enriched in the inflammatory pathways. In conclusion, the intracoronary application of nicorandil before PCI can regulate the inflammatory responses induced by PCI, which might be an important mechanism of nicorandil in preventing MNR.