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Objective:To explore the myocardial protective effect of nicorandil preoperative intervention on patients with heart disease undergoing hip replacement surgery.Methods:The case data of 117 patients undergoing hip arthroplasty in Rugao Branch Affiliated Hospital of Nantong University from June 2018 to December 2020 were retrospectively analyzed. According to whether nicorandil was given before surgery, they were divided into two groups. The group A and group B was given routine preoperative general anesthesia, and the group B was given nicorandil before surgery. The surgery-related indicators, inflammatory factors, myocardial damage, major adverse cardiac events (MACE) werecompared between the two groups.Results:The operation time, intraoperative blood loss, intraoperative fluid rehydration, urine output, Ramsay sedation score on the first day after surgery, visual analogue scale (VAS) score on the first day after surgery, and hospital stay in the two groups had no significant differences ( P>0.05). The levels of serum interleukin-6, tumor necrosis factor -α, C-reactive protein, cardiac troponin I, creatine kinase-MB, myoglobin andipoprotein associated phospholipase A2 postoperative in group B were lower than those in the group A: (388.15 ± 56.20) μg/L vs. (456.34 ± 65.18) μg/L, (34.24 ± 8.90) μg/L vs. (40.26 ± 10.22) μg/L, (27.54 ± 5.52) mg/L vs. (30.25 ± 5.61) mg/L, (0.10 ± 0.05) μg/L vs. (0.19 ± 0.08) μg/L, 0.059 ± 0.019 vs. 0.099 ± 0.026, (68.41 ± 6.03) μg/L vs. (76.61 ± 6.54) μg/L, (201.67 ± 25.88) μg/L vs. (251.37 ± 31.06) μg/L, the differences were statistically significant ( P<0.05). There was no statistically significant difference in the total incidence of MACE between the two groups ( P>0.05). Conclusions:Nicorandil intervention before hip replacement surgery can effectively improve the levels of inflammatory factors in patients with heart disease and reduce the degree of myocardial damage.Whether it can reduce the risk of MACE after surgery still needs to be further demonstrated.
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With the rapid development of imaging and percutaneous coronary intervention, the application of contrast media has become more and more widespread, and contrast-associated AKI has become one of the most common causes of acute kidney injury. Contrast-associated AKI seriously threatens patients' health and brings greater economic burden to patients, so it is particularly important to prevent the contrast-associated AKI. Nicorandil is a common vasodilator drug in clinical practice, widely used in the treatment of angina pectoris, with the effects of anti-oxidative stress, anti-apoptosis, anti-inflammatory and vasodilation, and is considered to be effective in preventing contrast - associated AKI. However, there is still a lack of further research on the efficacy of nicorandil in preventing contrast-associated AKI.
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Objective To observe the effects of Shexiang Baoxin pill combined with intracoronary injection of nicorandil on myocardial perfusion and short-term prognosis after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Methods 151 patients with acute myocardial infarction after PPCI were enrolled in this study. Those patients were admitted to our hospital during January 2017 to January 2018. According to the numerical randomization method, 51 patients were selected as routine treatment group (group A), 50 patients with intracoronary injection of nicorandil (group B) and 50 patients received intracoronary injection of nicorandil plus oral Shexiang Baoxin pills (group C). Intra-operative corrected TIMI frame count (cTFC), postoperative TIMI grade 3 blood flow ratio, 2-hour ECG ST segment fallback >50% index, the incidence of major adverse cardiovascular events (MACE) during hospitalization and the incidence of angina and MACE within 3 months after surgery were evaluated. Results cTFC, 2 hours postoperative ECG ST segment fall >50% index in group B and C were better than group A (P<0.05). The results from group C were better than group B. Group C exhibited better results than group B and C in post-operative angina pectoris 3 months after surgery (P<0.05). Conclusion Shexiang Baoxin pills combined with intra-coronary injection of nicorandil can improve myocardial perfusion and short-term prognosis after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction
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Nicorandil is a new vasodilator, which has the dual effects of nitrate like ester and ATP sensitive potassium channel (KATP channel) opening. Intracoronary injection of nicorandil can expand the coronary artery, protect the coronary microcirculation, and play an anti-inflammatory role, inhibit microthrombosis, increase myocardial perfusion and reduce the incidence of no reflow by acting on a variety of signal pathways; It can also reduce the infarct area and improve cardiac function; Through a variety of cell membrane enzyme signal pathways, it can significantly increase the outflow of potassium ions in cells, cause cell membrane hyperpolarization, inhibit the flow of calcium ions into cells and intracellular calcium overload, reduce the occurrence of abnormal reperfusion rhythm and reperfusion injury. Therefore, it has a good myocardial protective effect on patients with acute myocardial infarction.
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OBJECTIVE To syste matically evaluate the prevention effects of nicorandil on contrast-induced nephropathy in patients underwent coronary angiography （CAG）or stent implantation （CSI），and to provide evidence-based reference for clinical drug use. METHODS Retrieved from PubMed ，Embase，Cochrane library ，Wanfang database ，CBM and CNKI ，randomized controlled trial （RCT）about nicorandil （trial group ）versus normal saline or placebo （control group ）prevented contrast-induced nephropathy in patients underwent CAG or CSI were collected during the inception to Nov. 2021. After extracting literature that met the inclusion criteria ，the bias risk assessment tool of RCT in Cochrane manual was used for quality evaluation ，and meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 17 RCTs were included ，involving 3 279 patients. Among them，there were 1 587 patients in trial group ，and 1 692 patients in control group. Results of meta-analysis showed that the incidence of contrast-induced nephropathy in trial group was significantly lo wer than control group [RR ＝0.40，95％CI（0.31，0.51）， P＜0.000 1] . Results of subgroup analysis showed that the incidence of contrast-induced nephropathy in trial group was significantly lower than control group ，whether intravenous administration [RR ＝0.47，95％CI（0.29，0.74），P＝0.001] or oral administration [RR ＝0.37，95％CI（0.28，0.50），P＜0.000 01]，whether patients with normal renal function [RR ＝0.42，95％CI（0.30， 0.59），P＜0.000 01] or with renal insufficiency [RR ＝0.38， 95％ CI（0.26，0.54），P＜0.000 01]. Scr of 24 h[SMD＝ －1.38，95％CI（－2.32，－0.44），P＝0.004]，48 h[SMD＝ －0.81，95％CI（－1.19，－0.43），P＜0.000 1] and 72 h[SMD＝ －0.24，95％CI（－0.43，－0.05），P＝0.01] after surgery in trialgroup were significantly lower than control group ；the 163.com decrease of creatinine clearance rate of 48 h[SMD＝1.27， 95％CI（0.48，2.07），P＝0.001] and 72 h[SMD＝0.37，95％CI（0.07，0.67），P＝0.02] after surgery in trial group were significantly lower than control group ；cystatin C of 24 h[SMD＝－0.93，95％CI（－1.72，－0.14），P＝0.02]，48 h[SMD＝－1.72，95％CI （－2.33，－1.10），P＜0.000 01] and 72 h[SMD＝－0.36，95％CI（－0.62，－0.10），P＝0.006] after surgery in trial group were significantly lower than control group. CONCLUSIONS Pretreatment of nicorandil can reduce the incidence of contrast-induced nephropathy in patients underwent CAG or CSI ，and reduce the damage of renal function after application of contrast.
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Objective:To investigate the effects of nicorandil combined with thrombus aspiration during percutaneous coronary intervention on reperfusion arrhythmia in patients with acute ST-elevation myocardial infarction.Methods:180 patients with acute ST-elevation myocardial infarction who received treatment in Yidu Central Hospital, Weifang Medical University, China between January 2019 and June 2020 were included in this study. They were randomly assigned to receive either nicorandil combined with thrombus aspiration during percutaneous coronary intervention (NPCI group, n = 90) or conventional PCI (PPCI group, n = 90). Myocardial perfusion (myocardial blush grade 3 blood flow) and the occurrence of reperfusion arrhythmia within 24 hours after treatment were compared between the NPCI and PPCI groups. Results:The incidence of myocardial blush grade 3 blood flow in the NPCI group was significantly higher than that in the PPCI group [84.44% (76/90) vs. 68.88% (62/90), χ2 = 6.01, P = 0.01]. There was no significant difference in the total incidence of reperfusion arrhythmia between NPCI and PPCI groups ( χ2 = 1.19, P = 0.27). The incidence of severe reperfusion arrhythmia in the NPCI group was significantly lower than that in the PPCI group [13.33% (12/90) vs. 27.77% (25/90), χ2 = 5.75, P = 0.02]. The influential factor of severe reperfusion arrhythmia was analyzed by logistic regression taking whether NPCI treatment was used as the variable ( OR = 0.40, 95% CI 0.18-0.89, P = 0.02). The other factors that affect severe reperfusion arrhythmia included age ( OR = 0.71, 95% CI 0.19-0.92, P = 0.04), time from onset to reperfusion of infarct related artery ( OR = 0.62, 95% CI 0.21-0.98, P = 0.02), dcuhistory of pre-infarct angina pectoris ( OR = 0.67, 95% CI 0.19-0.98, P = 0.03), admission blood glucose level ( OR = 1.96, 95% CI 1.05-5.78, P = 0.03), admission leukocyte count ( OR = 1.99, 95% CI 1.02-6.18, P = 0.03) and cardiac function ( OR = 1.71, 95% CI 1.06-6.91, P = 0.04). Conclusion:Nicorandil combined with thrombus aspiration during percutaneous coronary intervention for the treatment of acute ST-elevation myocardial infarction can not only improve myocardial perfusion, but also reduce the incidence of reperfusion arrhythmia. The combined therapy is superior to monotherapy, has certain clinical significance and is innovative.
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Objective:To investigate the efficacy of Nicorandil in the treatment of unstable angina pectoris.Methods:Sixty patients with unstable angina pectoris who received treatment in Department of Cardiovascular Disease, Suixi Hospital of Traditional Chinese Medicine, China during January-July 2020 were included in this study. They were randomly assigned to receive either conventional treatment including antiplatelet, increasing coronal blood flow velocity, lipid-lowering treatment and stabilization of atherosclerotic plaque (control group, n = 30) or Nicorandil treatment and conventional treatment (observation group, n = 30). Clinical efficacy was compared between the two groups. Angina attack, electrocardiogram changes and adverse reactions in each group were analyzed before and after treatment. Results:Total effective rate in the observation group was significantly higher than that in the control group [88.67% (26/30) vs. 53.33% (16/30), χ2 = 7.937, P = 0.005]. The frequency and duration of angina pectoris in the observation group were (1.53 ± 0.62) times/week, (1.93 ± 0.78) minutes, which were significantly lower or shorter than those in the control group [(1.97 ± 0.71) times /week, (2.60 ± 1.00) minutes, t = -2.359, -3.162, P = 0.025, 0.004). The total effective rate of electrocardiogram in the observation group was significantly higher than that in the control group [70.00% (22/30) vs. 43.34% (13/30), χ2 = 5.554, P = 0.018]. There was no significant difference in the incidence of adverse drug reactions such as nausea, dizziness and palpitation between the two groups (all P > 0.05). Conclusion:Based on conventional treatment, Nicorandil treatment for unstable angina pectoris can improve the clinical symptoms and electrocardiogram changes, exhibit remarkable efficacy, and therefore deserve clinical promotion.
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OBJECTIVE：To systematically evaluate the effectiveness and safety of nicorandil combined with atorvastatin calcium in the treatment of unstable angina pectoris ，and to provide reference for clinical treatment. METHODS ：Retrieved from PubMed，Cochrane Library ，Embase database ，CBM，VIP，CNKI and Wanfang database ，randomized controlled trials （RCTs） about nicodil combined with atorvastatin calcium in the treatment of unstable angina pectoris were collected from the inception until Jan. 3rd，2021. The included studies were screened and evaluated with modified Jadad scale. Meta-analysis was performed by using Rev Man 5.3 software. RESULTS ：A total of 10 RCTs were included ，involving 1 123 patients. Meta-analysis results showed that compared with atorvastatin calcium group ，nitcodil combined with atorvastatin calcium group significantly increased angina response rate [OR ＝3.44，95％CI（2.35，5.04），P＜0.001]，the rate of electrocardiogram improvement [OR ＝4.93，95％CI（2.88， 8.43），P＜0.001]，and significantly reduced MMP- 9 level [SMD ＝－4.21，95％CI（－4.63，－3.80），P＜0.001]，incidence of recurrent angina pectoris [OR ＝0.30，95％CI（0.12，0.71），P＝0.006]，myocardial infarction rate [OR ＝0.27，95％CI（0.08，0.89）， P＝0.03]，the incidence of adverse cardiovascular events [OR ＝0.34，95％ CI（0.21，0.55），P＜0.001]. CONCLUSIONS ： Nicorandil combined with atorvastatin calcium shows better efficacy in the treatment of unstable angina pectoris in terms of effective rate of angina pectoris ，improvement rate of cardiogram ，MMP-9 level，incidence of recurrent angina pectoris and the incidence of myocardial infarction ，and has better safety in the incidence of adverse cardiovascular events. Due to the limitation of included studies ，it remains to be verified by RCT with large sample，multi-center and high quality.
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Blood–brain barrier (BBB) disruption, inflammation, and cell death are the pathogenic mechanisms of cerebralischemia/reperfusion (I/R) injury. Nicorandil protects ischemic injury via some of these mechanisms. The aimof this study was to investigate the therapeutic effects of this drug on the brain ischemia after transient middlecerebral artery occlusion (MCAO) and clarify the NF-jB and Nrf2-dependent mechanisms modulated by thisdrug. Sixty-six rats were randomized into sham, MCAO and MCAO ? nicorandil groups with oral gavage for3 days. Cerebral I/R injury were induced by a transient MCAO for 1 h and neurobehavioral scores wereperformed for 3 days. In addition to measurement of BBB disruption and brain water content, the total andinfarct volume, density, and total number of neurons, non-neurons and dead neurons in the right cortex wereestimated by unbiased stereological methods. RT-PCR was performed to analyze the expression levels of NFjB and Nrf2. Although nicorandil treatment in the sub-acute brain ischemia did not have a prominent effect onneurobehavioral function and number of neurons, non-neurons and dead neurons probably through up-regulation of NF-jB, it, however, improved ischemia-induced BBB disruption and brain edema and showed asignificant reduction in the infarction volume probably through up-regulation of Nrf2.
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OBJECTIVE：To evaluate the effects of nicorand il on the proliferation ，migration ability and Hippo/YAP signaling pathway of pulmonary artery smooth muscle cells （PASMCs）. METHODS ：Human primary PASMCs were divided into normal control group ，model group ，nicorandil low ，medium and high concentration groups （50，100，200 μmol/L），with 3 holes in each group. In addition to the normal control group ，the rest of the cells were inoculated on the gel coated medium to simulate the pulmonary hypertension environment ，so as to establish AS cell model. Then ，each drug group was added with corresponding drugs，and the normal control group and model group were added with the same volume of normal saline ，and cultured for 48 h. CCK-8 assay and Transwell assay were used for the examination of cell proliferation （by light density ）and migration ability ， respectively. mRNA expression of YAP target factors （CTGF and AREG ）were examined by qRT-PCR. Western blotting assay was used to detect the protein expression of CTGF and AREG. RESULTS ：Compared with normal control group ，light density of cells was increased significantly in model group ；the number of migration cells per field of view increased significantly ；mRNA and protein expression of CTGF and AREG were significantly increased （P＜0.01）. Compared with model group ，light density ，the number of migration cells per field of view ，mRNA and protein expression of CTGF and AREG in nicorandil low ，medium and high concentration groups were decreased significantly ， in concentration-dependent manner （P＜0.05 or P＜0.01）. CONCLUSIONS：Nicorandil can inhibit the proliferation and migration of PASMCs in AS model ，the mechanism of which cstc2019jscx-msxmX0174） may be associated with the Hippo/YAP signaling pathway.
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@#BACKGROUND: This study investigated the effects of the intracoronary injection of nicorandil and tirofiban on myocardial perfusion and short-term prognosis in elderly patients with acute ST-segment elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). METHODS: Seventy-eight STEMI patients with age >65 years who underwent emergency PCI were consecutively enrolled. These patients received conventional PCI and were randomly divided into a control group and a treatment group (n=39 per group). The control group received an intracoronary injection of tirofi ban followed by a maintenance infusion for 36 hours after surgery. The treatment group received intracoronary injection of tirofiban and nicorandil, and then intravenous infusion of tirofi ban and nicorandil 36 hours after surgery. The following parameters were measured: TIMI grade, corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG), STsegment resolution (STR) rate 2 hours post-operatively, resolution of ST-segment elevation (STR) at 2 hours postoperatively, peak level of serum CK-MB, left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) at 7–10 days postoperatively, and major adverse cardiac events (MACEs) in-hospital and within 30 days post-operatively. RESULTS: Compared with the control group, more patients in the treatment group had TIMI 3 and TMPG 3, and STR after PCI was significantly higher. The treatment group also had significantly lower cTFC, lower infarction relative artery (IRA), lower peak CK-MB, and no refl ow ratio after PCI. The treatment group had signifi cantly higher LVEDD and LVEF but lower incidence of MACEs than the control group. CONCLUSION: The intracoronary injection of nicorandil combined with tirofi ban can effectively improve myocardial reperfusion in elderly STEMI patients after emergency PCI and improve shortterm prognoses.
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Objective :To study influence of nicorandil on vascular endothelial function in patients undergoing selective percutaneous coronary intervention (PCI).Methods :The 184 patients with coronary heart disease (CHD) in our de‐partment were randomly and equally divided into routine group (received selective PCI combined routine medica‐tion) and nicorandil group (received nicorandil based on routine treatment group ).Myocardial injury indexes ,levels of endothelial function indexes and inflammatory factors ,fore brachial artery endothelium dependent diastolic‐sys‐tolic function (FMD) and reactive hyperemia diameter (D1) before and after treatment ,and incidence rate of major adverse cardiovascular events (MACE) were compared between two groups .Results :Compared with routine group on 7d after PCI ,there were significant reductions in levels of cardiac troponin I (cTnI) [ (0.25 ± 0.04) ng／ml vs . (0. 22 ± 0. 03) ng／ml] ,creatine kinase isoenzyme MB (CK‐MB) [ (14.15 ± 1.52) U／L vs.(11.87 ± 1.29) U／L] , heart type fatty acid binding protein (H‐FABP) [ (0.98 ± 0.14) ng／ml vs.(0.74 ± 0.11) ng／ml] , ET‐1 [ (67. 52 ± 6.93) pg／ml vs.(51. 27 ± 5. 30) pg／ml] ,hsCRP [(5. 98 ± 0. 62) mg／L vs.(3.68 ± 0.39) mg／L] and IL‐6 [(29. 31 ± 2.97) ng／L vs .(20. 94 ± 2. 22) ng／L] ,and significant rise in level of NO [ (61. 87 ± 6.42) pg／ml vs.(86. 24 ± 8.73) pg／ml] plasminogen activator inhibitor‐1 (PAI‐1) [ (129.95 ± 14.29) ng／L vs.(141. 27 ± 15.38) ng／L] in nicorandil group , P＝ 0.001 all ; compared with routine group , there were significant rise in FMD [ (14.50 ± 1.57)% vs.(18. 70 ± 1. 92)%] and D1 [(3.85 ± 0. 46) mm vs.(3. 99 ± 0.45) mm] ,and significant reduction in in‐cidence rate of MACE (35.87% vs.9. 78%) in nicorandil group on six months after PCI , P＜0.05 or ＜0.01. Con‐clusion :Nicorandil can protect vascular endothelium ,reduce myocardial injury ,eliminate inflammatory factors and reduce incidence rate of MACE in patients undergoing selective PCI .
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OBJECTIVE： To observe the effects of nicorandil on vascular endothelial function and angina pectoris recurrence in patients with unstable angina pectoris after percutaneous coronary intervention （PCI）. METHODS： Totally 195 patients with unstable angina pectoris were collected from Sichuan Provincial People’s Hospital during Jan. 2016-Mar. 2018， and then divided into control group （97 cases） and observation group （98 cases） according to random number table. Both groups received PCI， and then given basic treatment as Enoxaparin sodium injection， Isosorbide mononitrate sustained-release tablets， Aspirin enteric-coated tablets， Clopidogrel sulfate tablets and Atorvastatin calcium tablets after PCI. Observation group additional received Nicorandil tablet 5 mg， tid， on the basis of control group. Both groups were treated for 6 months. The levels of vascular endothelial function related indexes （FMD， ET-1， NO）， myocardial injury markers （cTnⅠ， CK-MB） and inflammatory factors （hs-CRP） were observed before and after PCI. The recurrent angina pectoris， the occurrence of MACE and ADR were recorded. RESULTS： 6 patients of control group and 4 patients of observation group withdrew from the study. One day before operation， there was no significant difference in the levels of vascular endothelial function， myocardial injury markers or inflammatory factors between 2 groups （P＞0.05）. One day after operation， the levels of FMD and NO in both groups decreased significantly， while the levels of ET-1， cTnⅠ and CK-MB increased significantly （P＜0.05）. The levels of FMD and NO were increased significantly in the 1st and 6th months after surgery， and the observation group was significantly higher than the control group； the levels of ET-1， cTnⅠ， CK-MB and hs-CRP were decreased significantly， and the observation group was significantly lower than the control group （P＜0.05）. The incidence and times of recurrent angina pectoris， duration， the proportion of grade Ⅲ angina pectoris and total incidence of MACE in observation group were significantly lower， less or shorter than control group （P＜0.05）. There was no statistical significance in total incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS： Additional use of nicorandil can improve vascular endothelial function， relieve the myocardial injury and inflammatory response， reduce the occurrence of recurrent angina pectoris and MACE after PCI and doesn’t influence the safety of routine treatment.
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To observe therapeutic effect of early use of nicorandil on patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) and its influence on cardiac function .Methods : A total of 124 MI patients undergoing PCI in our hospital from 2016 to 2018 were randomly and equally divided into PCI group and nicorandil + PCI group (received nicorandil based on PCI group ) , both groups were treated for 28d. Therapeutic effect , incidence of adverse , LVEF , LVEDd and cardiac index (CI) before and three months after PCI were recorded and compared between two groups .Results : Compared with PCI group , there was significant rise in total effective rate (72.6% vs .90.3%) , and significant reductions in incidence rates of recurrent angina pectoris (25.8% vs.11.3%) and malignant arrhythmia (22.6% vs.8.1%) in nicorandil + PCI group , P＜0. 05 all.Compared with before PCI , there were significant rise in LVEF and CI , and significant reduction in LVEDd in two groups on three months after PCI ;compared with PCI group , there were significant rise in LVEF [ (40.52 ± 4.38)% vs.(46.81 ± 4.53)%] and CI [ (2.43 ± 0.35) L·min－1 ·m－2 vs.(2.66 ± 0.38) L·min－1 ·m－2 ] , and significant reduction in LVEDd [ (54. 32 ± 6.23) mm vs.(48. 24 ± 5.34) mm] in nicorandil + PCI group on three months after PCI , P＝0.001 all.There was no significant difference in incidence rate of adverse drug reactions dur‐ing treatment between two groups , P＝0.753. Conclusion : Early use of nicorandil can significantly improve thera‐peutic effect , contribute to recovery of cardiac function with good safety in MI patients undergoing PCI , which is worth extending .
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Objective :To study influence of nicorandil on vascular endothelial function and serum inflammatory reac-tion in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI).Methods :A total of 118 CHD patients undergoing PCI in our hospital were randomly divided into routine treatment group (n＝58) and nicorandil group (n＝60 ,received nicorandil based on routine treatment ) ,both groups were treated for six months .Endothelial function ,levels of inflammatory factors and myocardial injury markers before and after treatment ,and incidence of major adverse cardiovascular events (MACE) were observed and compared between two groups.Results : Compared with routine treatment group after treatment ,there were significant rise in radial artery reactive hyperemia inner diameter [D1 ,(3-83 ± 0-37) mm vs.(4-01 ± 0-39) mm] ,flow-mediated dilation of bra-chial artery [FMD ,(14-33 ± 1-42 )% vs.(19-35 ± 1-95 )%] ,serum levels of nitric oxide [NO , (70-72 ± 7-82 ) μmol／L vs .(86-15 ± 8-52) μmol／L] and interleukin-10 [IL-10 ,(392-86 ± 40-19) ng／ml vs.(472-75 ± 48-62) ng／ml] ,and significant reductions in serum levels of endothelin-1 [ET-1 ,(70-29 ± 7-39) ng／L vs.(59-62 ± 6-02) ng／L ] ,intercellular adhesion molecule-1 [ICAM-1 ,(195-68 ± 20-48) μg／L vs.(146-72 ± 15-07) μg／L] ,cardiac tropo-nin I [cTnI ,(0-471 ± 0-071) ng／ml vs.(0-222 ± 0-052) ng／ml] ,creatine kinase isoenzyme MB [CK-MB ,(27-62 ± 3-72) U／L vs.(14-79 ± 1-52) U／L] ,mean platelet volume [MPV ,(10-26 ± 1-06) fl vs.(9-75 ± 0-95) fl] ,high sensitive C reactive protein [hsCRP , (5-36 ± 0-63 ) mg／L vs.(3-08 ± 0-27 ) mg／L ] , in-stent restenosis rate (20-69% vs.1-67%) and incidence rate of MACE (67-24% vs.10-00%) in nicorandil group ,P＜0-05 or ＜0-01-Conclusion : Nicorandil can improve postoperative endothelial function ,reduce inflammatory reaction ,protect myo-cardial cells with good prognosis in CHD patients undergoing PCI ,which is worth extending .
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To study the effect of nicorandil pretreatment on ketone body metabolism and Acetyl-CoA acetyltransferase (ACAT1) activity in hypoxia/reoxygenation (H/R)-induced cardiomyocytes. In our study, we applied H9c2 cardiomyocytes cell line to evaluate the cardioprotective effects of nicorandil. We detected mitochondrial viability, cellular apoptosis, reactive oxygen species (ROS) production and calcium overloading in H9c2 cells that exposed to H/R-induced cytotoxicity. Then we evaluated whether nicorandil possibly regulated ketone body, mainly β-hydroxybutyrate (BHB) and acetoacetate (ACAC), metabolism by regulating ACAT1 and Succinyl-CoA:3-keto-acid coenzyme A transferase 1 (OXCT1) protein and gene expressions. Nicorandil protected H9c2 cardiomyocytes against H/R-induced cytotoxicity dose-dependently by mitochondria-mediated anti-apoptosis pathway. Nicorandil significantly decreased cellular apoptotic rate and enhanced the ratio of Bcl-2/Bax expressions. Further, nicorandil decreased the production of ROS and alleviated calcium overloading in H/R-induced H9c2 cells. In crucial, nicorandil upregulated ACAT1 and OXCT1 protein expressions and either of their gene expressions, contributing to increased production of cellular BHB and ACAC. Nicorandil alleviated cardiomyocytes H/R-induced cytotoxicity through upregulating ACAT1/OXCT1 activity and ketone body metabolism, which might be a potential mechanism for emerging study of nicorandil and other K(ATP) channel openers.
Subject(s)
Acetyl-CoA C-Acetyltransferase , Apoptosis , Calcium , Cell Line , Coenzyme A , Gene Expression , Metabolism , Myocytes, Cardiac , Nicorandil , Reactive Oxygen Species , TransferasesABSTRACT
Background: Diabetes increases the risk of macrovascular complications and is often associated with angina in patient. Currently nicorandil, a potassium channel opener is being frequently used for the prevention and long-term treatment of angina pectoris. Glibenclamide exerts its antidiabetic action by closing the ATP sensitive potassium channels. Simultaneous use of nicorandil may antagonizes this action and may worsens the existing diabetes. To evaluate the pharmacodynamic interaction present study has been taken to study the effect of Nicorandil, a potassium channel opener on blood glucose level of alloxan induced diabetic rats and its pharmacodynamics interaction with Glibenclamide.Methods: Albino rats, weighing 150-200gm of male sex were used for the study. Diabetes was induced by injecting alloxan monohydrate 2% solution intra peritoneally in a dose of 150mg/kg body weight. Animal with Fasting Blood Sugar level between 250-300g/dl was selected for study and they were divided into 4 groups of 5 animals each. Group I- serving as control received 0.5ml normal saline orally for 28 days. Group II was given glibenclamide (0.5mg/kg body wt) for 28 days. Group III was treated orally with nicorandil (0.3mg/kg body wt) for 28 days. Group IV was given glibenclamide (0.5mg/kg) and nicorandil (0.3mg/kg) for 28 days. Fasting Blood Sugar level was recorded in all rats on 1st,3rd,7th,14th,21st and 28th day of the treatments.Results: results showed that glibenclamide significantly reduce blood sugar level (p <0.05) Wherase nicorandil showed rise in blood glucose level (p <0.05) While the combination (glibenclamide + nicorandil) showed rise in blood glucose (p <0.05) overall.Conclusions: Nicorandil worsen the existing diabetes and to be avoided or replaced with alternative drug in case of diabetes being treated with sulfonyl urease group of drugs.
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@#Objective Toevaluatetheeffectsofcombinedintracoronaryandintravenous administrationofnicorandil onmyocardialmicrocirculationandshort-termprognosisinpatientswithacuteST-segmentelevationmyocardialinfarction (STEMI)treatedwithprimarypercutaneouscoronaryintervention(PPCI). Methods Atotalof100patientswithacute STEMIunderwentPPCIwererandomlydividedintothenicorandilgroup(patientsreceivedintracoronarybolusinjectionof nicorandilwhenthetargetvesselopenedandthencontinuousintravenousinfusionwithin24hours, n=50)andthecontrol group(patientsreceivednormalsalineascontrol, n=50).Themainoutcomemeasureswereimmediatecoronaryflowand myocardialperfusionafterPPCI,includingthrombo-Lysisinmyocardialinfarction(TIMI)flowgrade,correctedTIMIframe count(CTFC),reperfusionarrhythmia,ST-segmentresolution,plasmacreatinekinaseisoenzyme(CK-MB)peakvalueand time. The secondary indicators were major adverse cardiovascular events (MACE) and left ventricular ejection fraction (LVEF)duringhospitalization.Results Therewerenosignificantdifferencesinhepatorenalfunction,heartrateandblood pressurebeforeandafteroperationineachgroup(P＞0.05).Theincidenceofreperfusionarrhythmia,thelevelofMACE, CTFC,andpeakvalueofCK-MBwereallsignificantlylowerinthenicorandilgroupcomparedwiththoseofcontrolgroup (P＜0.05).TheproportionsofpatientswithTIMI3flow,CK-MBpeaktimein14hours,andtheproportionofST-segment resolutionweresignificantlyhigherinthenicorandilgroupthanthoseofthecontrolgroup(all P＜0.05).Therewasno significant difference in LVEF during hospitalization between two groups (P＞0.05). Conclusion Intracoronary and intravenousadministrationofnicorandilcansignificantlyimproverevascularizationeffects,reducetheoccurrenceofslow flow/noreflow,limitmyocardialinfarctionsize,increasemyocardialperfusionandimprovemyocardialmicrocirculationand theshort-termprognosisofacuteSTEMIpatients.
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Objective To study the role of different dose nicorandil in prevention of CIN in elderly CHD patients.Methods One hundred and twenty-one elderly CHD patients were divided into standard dose nicorandil treatment group (n=42),5 mg nicorandil treatment group (n=39) and 10 mg nicorandil treatment group (n=40).Their Scr levels,and eGFR were measured for 3 days before and after PCI.The urine KIM-1 and NGAL levels were measured before and 24 h after PCI.The incidence of CIN and adverse reactions were compared in 3 groups.Results The incidence of (IN and the eGFR ≥25％ were significantly lower,the serum Scr level was significantly lower while the eGFR was significantly higher in 5 mg and 10 mg nicorandil treatment groups than in standard dose nicorandil treatment group on days 1 and 2 after PCI (P＜0.05,P＜0.01).The serum Scr level was significantly lower while the eGFR was significantly higher in 10 mg nicorandil treatment group than in 5 mg nicorandil treatment group on day 2 after PCI (P＜0.05).The urine KIM-1 and NGAL level were significantly lower in 10 mg nicorandil treatment group than in standard dose nicorandil treatment group and 5 mg nicorandil treatment group at 24 h after PCI (2.77±0.33 μg/L vs 5.63±0.27 μg/L,4.82±0.32 μg/L,P＜0.05;41.64±8.42 μg/L vs 66.51±10.72 μg/L,57.11±9.67 μg/L,P＜0.05).Conclusion Different oral doses of nicorandil play a role in prevention of CIN and 10 mg nicorandil plays a greater role than standard dose nicorandil and 5 mg nicorandil in prevention of CIN in elderly CHD patients undergoing PCI.