BACKGROUND Coronary artery disease(CAD)is a leading cause of global cardiovascular morta-lity.Refractory angina pectoris,a manifestation of CAD,requires effective drug treatments.Pericarpium Trichosanthis injection,a ...BACKGROUND Coronary artery disease(CAD)is a leading cause of global cardiovascular morta-lity.Refractory angina pectoris,a manifestation of CAD,requires effective drug treatments.Pericarpium Trichosanthis injection,a traditional Chinese medicine,improves cardiovascular symptoms,while nicorandil alleviates spasms and angina.Both have potential in treating CAD.AIM To investigate the therapeutic effects of combining Pericarpium Trichosanthis injection and nicorandil in elderly patients suffering from refractory angina caused by coronary heart disease.METHODS A retrospective analysis was conducted on the data of 130 patients diagnosed with refractory coronary heart disease.Based on the different treatment regimens administered during hospitalization,the patients were divided into a control group(58 cases)and a study group(72 cases).The control group received conven-tional treatment,which included aspirin,statins,and nitrate vasodilators.In addition to the conventional medication,the study group received a combination treatment of Pericarpium Trichosanthis injection and nicorandil.RESULTS After treatment,the study group showed significantly higher left ventricular ejection fraction and cardiac output,and lower brain natriuretic peptide and C-reactive protein levels compared to the control group.The study group also exhibited improvements in angina,quality of life,exercise endurance,and lipid profiles.Multivariate logistic regression analysis revealed a relationship of lipid levels and heart function with the combined treatment.Some patients in the study group experienced headaches during treatment,but no significant adverse reactions were observed.Follow-up showed that the treatment was well-tolerated,with no drug-related adverse reactions detected.CONCLUSION Combination of Pericarpium Trichosanthis injection and nicorandil is more effective than conventional treatment in improving symptoms and heart function in elderly patients with refractory angina pectoris.展开更多
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...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 tirofiban 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 tirofiban and nicorandil 36 hours after surgery.The following parameters were measured:TIMI grade,corrected TIMI frame count(c TFC),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 c TFC,lower infarction relative artery(IRA),lower peak CK-MB,and no reflow ratio after PCI.The treatment group had significantly higher LVEDD and LVEF but lower incidence of MACEs than the control group.CONCLUSION:The intracoronary injection of nicorandil combined with tirofiban can effectively improve myocardial reperfusion in elderly STEMI patients after emergency PCI and improve shortterm prognoses.展开更多
Background Nicorandil (NIC) is a vasodilatory drug used to treat angina. However, its efficacy of cardioprotection in coronary mi- croembolization (CME) is largely unknown. This study was undertaken to determine w...Background Nicorandil (NIC) is a vasodilatory drug used to treat angina. However, its efficacy of cardioprotection in coronary mi- croembolization (CME) is largely unknown. This study was undertaken to determine whether nicorandil pretreatment could attenuate myo- cardial apoptosis and improve cardiac function after CME in rats. Methods Forty-five rats were randomly divided into a Sham group, a CME group and a CME + NIC (NIC) group (n = 15 per group). CME was established by injecting plastic microspheres (42 pm in diameter) into the left ventricle of the rats in all of the groups except the Sham group. The NIC group received nicorandil at 3 mg/kg per day for seven days before the operation. Cardiac fimction was assessed by echocardiography, the expression levels of cleaved caspase-9/8/3 were detected by Western blot, microinfarction area was measured by haematoxylin-basic fuchsin picric acid staining, and myocardial apoptosis was de- tected by TUNEL staining. Results Compared to that in the Sham group, cardiac fimction in the CME group was significantly decreased (P 〈 0.05). However, compared to the CME group, the NIC group showed improved cardiac function (P 〈 0.05). The expression levels of cleaved caspase-9/8/3 protein and myocardial apoptosis were dramatically increased in the CME group compared to those in the Sham group (P 〈 0.05), while the NIC pretreatment group had significantly decreased expression levels of cleaved caspase-9/8/3 protein as well as a de- creased apoptotic rate (P 〈 0.05). Conclusions NIC pretreatment inhibited CME-induced myocardial apoptosis and improved cardiac func- tion through blockade of the mitochondrial and death receptor-mediated apoptotic pathways.展开更多
Previous studies have shown that nicorandil has a protective effect on cardiomyocytes.However,there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct siz...Previous studies have shown that nicorandil has a protective effect on cardiomyocytes.However,there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct size in patients with ST-segment elevation myocardial infarction(STEMI)compared to the current standard of percutaneous coronary intervention(PCI)regimen.The CHANGE(China-Administration of Nicorandil Group)study is a multicenter,prospective,randomized,double-blind and parallel-controlled clinical study of STEMI patients undergoing primary PCI in China,aiming to evaluate the efficacy and safety of intravenous nicorandil in ameliorating the myocardial infarct size in STEMI patients undergoing primary PCI and provide evidence-based support for myocardial protection strategies of STEMI patients.展开更多
BACKGROUND:Neurological injury is a common complication in the early period after liver transplantation,posing an enormous obstacle to treatment efficiency and patient survival.Nicorandil is a mitochondrial ATP-sensit...BACKGROUND:Neurological injury is a common complication in the early period after liver transplantation,posing an enormous obstacle to treatment efficiency and patient survival.Nicorandil is a mitochondrial ATP-sensitive potassium channel(mitoK ATP) opener.It has been reported to be effective in reducing brain injury in recent studies.However,it is still unclear whether nicorandil has cerebral protective effect in patients undergoing liver transplantation.METHODS:Fifty patients scheduled for liver transplantation were randomly divided into a nicorandil group(group N)(n=25),in which patients received 10 mg nicorandil through a nasogastric tube 30 minutes before induction of anesthesia,and a control group(group C)(n=25) who received 10 mL normal saline.The Mini-Mental State Examination(MMSE) was performed before anesthesia(day 0),and on days 3 and 7 after surgery.Blood samples were obtained before induction of anesthesia(T1),and at 12(T2) and 36 hours(T3) after surgery for determination of serum neuron-specific enolase(NSE) and S100β protein(S100β) concentrations.RESULTS:During surgery,5 patients in each group were eliminated due to severe reperfusion or renal insufficiency.Therefore,20 patients remained in each group.The MMSE scores after operation were significantly lower than those before operation in group C.However,there was no difference at days 3 and 7 compared with day 0 in group N.Serum NSE concentrations after surgery were significantly higher than baseline(at T1) in both groups,except at T3 in group N.Serum S100β concentration after surgery was significantly higher than baseline(at T1) in both groups.The MMSE scores at days 3 and 7 in group N were significantly higher than those in group C.The concentrations of serum NSE and S100β at T2 and T3 in group N were significantly lower than those in group C.CONCLUSIONS:Oral nicorandil,as a premedication before liver transplantation,improves postoperative MMSE scores.It also attenuates the increase of NSE and S100β in blood,indicating its cerebral protective effect.展开更多
A rapid and sensitive HPLC-DAD method is developed for simultaneous determination of nicorandil and its degradation products, N-(2-hydroxyethyl) nicotinamide, nitrate ion and nicotinic acid, using nicotinamide (NT...A rapid and sensitive HPLC-DAD method is developed for simultaneous determination of nicorandil and its degradation products, N-(2-hydroxyethyl) nicotinamide, nitrate ion and nicotinic acid, using nicotinamide (NT) as internal standard, at wavelength 204 nm. Nicotinic acid is identified by HPLC and GC/MS. The method can also be applied to study kinetic of degradation processes of nicorandil in storage.展开更多
The aim of this study was to design and evaluate extended-release formulations of a model drug,nicorandil,in order to achieve the desired steady-state plasma concentration of drug in vivo.Simulation was employed to es...The aim of this study was to design and evaluate extended-release formulations of a model drug,nicorandil,in order to achieve the desired steady-state plasma concentration of drug in vivo.Simulation was employed to estimate optimum dissolution and absorption rate of nicorandil.The dissolution test was employed using pH 1.2,4.0,6.8 buffer solution,or water,to measure the in vitro release behaviors of nicorandil formulations.A single dose(15 mg)of each formulation was orally administered to four beagle dogs under fasted conditions,and the pharmacokinetic parameters were calculated.The in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle dogs.Nicorandil was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release tablets.The nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release formulation.The release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extendedrelease formulations.These results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.展开更多
For the surgical treatment of cardiovascular disease(CVD),there is a clear and unmet need in developing small-diameter(diameter<6 mm)vascular grafts.In our previous work,sulfated silk fibroin(SF)was successfully fa...For the surgical treatment of cardiovascular disease(CVD),there is a clear and unmet need in developing small-diameter(diameter<6 mm)vascular grafts.In our previous work,sulfated silk fibroin(SF)was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility.However,vascular graft with single layer is difficult to adapt to the complex internal environment.In this work,polycaprolactone(PCL)and sulfated SF were used to fabricate bilayer vascular graft(BLVG)to mimic the structure of natural blood vessels.To enhance the biological activity of BLVG,nicorandil(NIC),an FDA-approved drug with multi-bioactivity,was loaded in the BLVG to fabricate NIC-loaded BLVG.The morphology,chemical composition and mechanical properties of NIC-loaded BLVG were assessed.The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior.The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation,migration and antioxidation capability of endothelial cells(ECs).Moreover,we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway.Overall,the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.展开更多
Background: Reduction of myocardial reperfusion injury during cardiopulmonary bypass is an essential requirement for increasing the success rate, decreasing morbidity and mortality of open-heart surgery. Aim: To study...Background: Reduction of myocardial reperfusion injury during cardiopulmonary bypass is an essential requirement for increasing the success rate, decreasing morbidity and mortality of open-heart surgery. Aim: To study the role of pre-operative oral nicorandil in decreasing reperfusion cardiac injury in patients subjected to cardiac valve surgery. Patients and Methods: The study included 62 patients, who were equally randomized into two groups: nicorandil group and control group. Pre-operative, intra-operative and post- operative data were reported and analyzed. Left Ventricle Ejection Fraction (LVEF) was estimated pre-operatively and postoperatively for both groups. Troponin I, creatine kinase-muscle/brain (CK-MB), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured before surgery by 24 hours then 4, 12 and 48 hours after aortic cross clamp removal. Results: Nicorandil considerably decreased TNF-α and IL-6 after 4 and 12 hours following the removal of aortic clamping. It also reduced troponin-I and CKMB at the same time points. However, there were no important changes in IL-6, TNF-α, troponin-I and CK-MB levels in control group in comparison to nicorandil group in the next 48 hours following the removal of aortic clamping. Conclusions: Pre-operative oral nicorandil expressively decreased myocardial reperfusion damage during open heart valve operations, this evidenced by the decrease in the postoperative use of inotropic drugs, considerable reduction of postoperative elevation of cardiac enzymes and inflammatory cytokines with no reported complications.展开更多
Aim:The effects of tirofiban combined with nicorandil on effective reperfusion,and the levels of interleukin-4(IL-4)and soluble intercellular adhesion molecule-1(sICAM-1)after percutaneous coronary intervention(PCI)fo...Aim:The effects of tirofiban combined with nicorandil on effective reperfusion,and the levels of interleukin-4(IL-4)and soluble intercellular adhesion molecule-1(sICAM-1)after percutaneous coronary intervention(PCI)for chronic coronary total occlusion(CTO)were investigated.Method:From January 1,2017,to June 31,2019,a total of 40 patients with CTO receiving PCI in Shandong Qian-foshan Hospital were randomly divided into a control group(treated with single tirofiban)and a cocktail group(treated with nicorandil combined with tirofiban).Effective reperfusion was compared between groups.In addition,differences in coronary serum IL-4 and sICAM-1 levels before and 10 min after the operation were compared between groups,and the incidence rates of adverse reactions were observed.Finally,patient follow-up occurred at 1 month and 6 months,and the total incidence rates of adverse cardiac events in both groups were assessed.Results:The levels of IL-4 and sICAM-1 in the cocktail group significantly decreased after the operation(P<0.05).In addition,after the operation,significantly greater decreases in the IL-4 and sICAM-1 levels were observed in the cocktail group than the control group(P<0.05).The Seattle Angina Scale(SAQ)score of the cocktail group,compared with the control group,showed a significant improvement after vessel opening in the patients with CTO.At the 1-month follow-up,the SAQ score of the cocktail group,compared with the control group,indicated further improvements in terms of angina attack frequency.No significant differences were observed in the incidence rates of adverse reactions between groups(P>0.05).Conclusion:The treatment of patients with CTO undergoing PCI with nicorandil and tirofiban alleviated the inflam-matory response,improved the SAQ scores,and decreased the occurrence of angina pectoris in patients.Moreover,this treatment is safe and reliable,and has important clinical significance.展开更多
Objective:To study the effect of nicorandil on postoperative myocardial injury, platelet function and inflammatory response in patients with slow reflow in PCI.Methods: Patients who underwent emergency PCI and had int...Objective:To study the effect of nicorandil on postoperative myocardial injury, platelet function and inflammatory response in patients with slow reflow in PCI.Methods: Patients who underwent emergency PCI and had intraoperative slow reflow in Zigong Fourth People's Hospital between March 2015 and August 2017 were selected and divided into nicorandil group and normal control group according to the application of nicorandil after no reflow or not in the history data. The levels of myocardial injury indexes in serum as well as the expression of platelet activation molecules and inflammatory signaling molecules in peripheral blood were measured before PCI as well as 1 day and 3 days after PCI.Results: Compared with the corresponding indexes of same group before PCI, serum H-FABP, HIF-1α, CK-MB and cTnⅠlevels as well as peripheral blood PAR1, PAR4, CCR2, p38MAPK, HSP27, Notch1, NF-κB, MEK1, ERK1/2 and CaMKⅡ mRNA expression of both groups of patients were significantly lower 1 day and 3 days after PCI, and serum H-FABP, HIF-1α, CK-MB and cTnⅠ levels as well as peripheral blood PAR1, PAR4, CCR2, p38MAPK, HSP27, Notch1, NF-κB, MEK1, ERK1/2 and CaMKII mRNA expression of nicorandil group 1 day and 3 days after PCI were significantly lower than those of normal control group.Conclusions:Nicorandil has negative regulating effect on postoperative myocardial injury, platelet activation and inflammatory response activation in patients with slow reflow in PCI.展开更多
Objective:To study the effect of adjuvant nicorandil therapy on inflammation, plaque stability and platelet function in patients with unstable angina.Methods:A total of 134 patients with unstable angina who received d...Objective:To study the effect of adjuvant nicorandil therapy on inflammation, plaque stability and platelet function in patients with unstable angina.Methods:A total of 134 patients with unstable angina who received drug therapy in our hospital between March 2015 and March 2016 were selected as the research subjects and randomly divided into the experimental group who accepted nicorandil combined with conventional therapy and the control group who accepted conventional therapy. 2 weeks after treatment, serum inflammation indexes and plaque stability indexes as well as peripheral blood platelet function parameters were determined.Results:2 weeks after treatment, serum hs-CRP, TNF-α, IL-18, IL-23, MMP1, MMP2, MMP3, MMP9 and ICTP levels of experimental group were significantly lower than those of control group;peripheral blood CD63, PAC-1, CD42b and GP-VI fluorescence intensity as well as Angle, MA and CI levels of experimental group were significantly lower than those of control group while R and K levels were significantly higher than those of control group.Conclusion:Adjuvant nicorandil therapy can relieve the inflammatory response in patients with unstable angina, and thereby inhibit the inflammation-mediated fibrous cap degradation, plaque stability decrease, platelet activation and thrombosis.展开更多
Objective:To explore the effect of nicorandil on the coronary artery microcirculation and hemodynamics in patients with coronary slow flow (CSF).Methods: A total of 86 patients with CSF who were admitted in our hospit...Objective:To explore the effect of nicorandil on the coronary artery microcirculation and hemodynamics in patients with coronary slow flow (CSF).Methods: A total of 86 patients with CSF who were admitted in our hospital were included in the study and randomized into the treatment group and the control group with 43 cases in each group. The patients in the control group were given aspirin, HMG-CoA reductase inhibitor, and ACEI. On this basis, the patients in the treatment group were given nicorandil. The patients in the two groups were continuously treated for 6 months. The coronary artery microcirculation and hemodynamic indicators before and after treatment in the two groups were detected and compared.Results:TAT, ET-1, and hs-CRP levels, LAD, LCX, RCA, TIMI average blood flow frame count value, and IMR after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05). The above indicators after treatment in the treatment group were significantly lower than those in the control group (P<0.05). FMD after treatment in the two groups was significantly elevated when compared with before treatment (P<0.05). FMD after treatment in the treatment group was significantly higher than that in the control group (P<0.05). Conclusions: Nicorandil in the treatment of CSF can effectively improve the coronary artery microcirculation and hemodynamics, with a significant efficacy.展开更多
Objective: To observe the influence of nicorandil combined with creatine phosphate sodium on serum BNP, CK-MB, cTnl, SOD, MMP-9 and cardiac function in patients with STEMI. Methods: A total of 60 patients with STEMI w...Objective: To observe the influence of nicorandil combined with creatine phosphate sodium on serum BNP, CK-MB, cTnl, SOD, MMP-9 and cardiac function in patients with STEMI. Methods: A total of 60 patients with STEMI were randomly divided into observation group (30 cases) and control group (30 cases). Observation group: nicorandil combined with creatine phosphate sodium;control group: patients were treated only by nicorandil. Recording and comparing the levels of BNP, CK-MB, cTnl, SOD, MMP-9 and cardiac function before and after treatment. Results: (1) Before treatment, there was no statistically significant difference in the serum BNP, CK-MB, cTnl, SOD, MMP-9 levels between the two groups. After treatment, compared with the same group before treatment, the serum BNP, CK-MB, cTnl, MMP-9 levels of the two groups were significantly lower, the serum SOD level of the two groups were significantly higher, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups. (2) Before treatment, there was no statistically significant difference in LVEF, WMSI, CI between the two groups. After treatment, compared with the same group before treatment, the WMSI of the two groups were significantly lower, the LVEF and CI of the two groups were significantly higher, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups. Conclusion: Nicorandil combined with creatine phosphate sodium for patients with STEMI can perfect the levels of serum BNP, CK-MB, cTnl, SOD, MMP-9 and be beneficial to protect their cardiac function.展开更多
Objective::Residual cardiovascular risk in patients with coronary heart disease(CHD)still needs to be addressed in real-world practice.This study aimed to examine the clinical effectiveness of nicorandil and nitrate i...Objective::Residual cardiovascular risk in patients with coronary heart disease(CHD)still needs to be addressed in real-world practice.This study aimed to examine the clinical effectiveness of nicorandil and nitrate in addition to optimal treatment for CHD patients.Methods::This retrospective cohort study included patients with CHD between October 2009 and March 2020 from 2 tertiary hospitals in Wuhan,China.Patients were grouped into nicorandil and nitrate groups depending on the first recorded antianginal therapy.Demographic and clinical data were collected from databases of the 2 hospitals.The primary outcome was cumulative 18-month major adverse cardiovascular event(MACE)-free survival,which was evaluated by Kaplan-Meier analysis.Propensity score matching(PSM)and multivariate Cox regression were adopted to adjust for confounding factors.Results::A total of 14,275 patients were analyzed,including 590 and 13,685 patients in the nicorandil and nitrate groups,respectively.With a median follow-up of 0.88(Q1,Q3:0.21,1.54)years,the cumulative 18-month MACE-free survival rates were comparable between the 2 groups(80.0%vs.75.0%,adjusted hazard ratio(aHR):1.04,95%confidence interval(CI):0.42-2.56,P=0.982,7)after 1:4 PSM.The cumulative 18-month stroke-free survival rate was significantly higher in the nicorandil group compared to the nitrate group(93.0%vs.84.0%,aHR:0.56,95%CI:0.34-0.92,P=0.023,5).Conclusion::This retrospective study showed that nicorandil and nitrate have similar 18-month rates of MACEs in CHD patients,but nicorandil is associated with lower incidence of stroke compared to nitrate.More studies need to be conducted to validate this association and explore the long-term benefit of nicorandil use on the occurrence of MACEs in the future.展开更多
文摘BACKGROUND Coronary artery disease(CAD)is a leading cause of global cardiovascular morta-lity.Refractory angina pectoris,a manifestation of CAD,requires effective drug treatments.Pericarpium Trichosanthis injection,a traditional Chinese medicine,improves cardiovascular symptoms,while nicorandil alleviates spasms and angina.Both have potential in treating CAD.AIM To investigate the therapeutic effects of combining Pericarpium Trichosanthis injection and nicorandil in elderly patients suffering from refractory angina caused by coronary heart disease.METHODS A retrospective analysis was conducted on the data of 130 patients diagnosed with refractory coronary heart disease.Based on the different treatment regimens administered during hospitalization,the patients were divided into a control group(58 cases)and a study group(72 cases).The control group received conven-tional treatment,which included aspirin,statins,and nitrate vasodilators.In addition to the conventional medication,the study group received a combination treatment of Pericarpium Trichosanthis injection and nicorandil.RESULTS After treatment,the study group showed significantly higher left ventricular ejection fraction and cardiac output,and lower brain natriuretic peptide and C-reactive protein levels compared to the control group.The study group also exhibited improvements in angina,quality of life,exercise endurance,and lipid profiles.Multivariate logistic regression analysis revealed a relationship of lipid levels and heart function with the combined treatment.Some patients in the study group experienced headaches during treatment,but no significant adverse reactions were observed.Follow-up showed that the treatment was well-tolerated,with no drug-related adverse reactions detected.CONCLUSION Combination of Pericarpium Trichosanthis injection and nicorandil is more effective than conventional treatment in improving symptoms and heart function in elderly patients with refractory angina pectoris.
文摘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 tirofiban 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 tirofiban and nicorandil 36 hours after surgery.The following parameters were measured:TIMI grade,corrected TIMI frame count(c TFC),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 c TFC,lower infarction relative artery(IRA),lower peak CK-MB,and no reflow ratio after PCI.The treatment group had significantly higher LVEDD and LVEF but lower incidence of MACEs than the control group.CONCLUSION:The intracoronary injection of nicorandil combined with tirofiban can effectively improve myocardial reperfusion in elderly STEMI patients after emergency PCI and improve shortterm prognoses.
基金This work received the support of the National Natural Science Foundation of China (Grant No. 81600283) and the Guangxi Natural Science Foundation (Grant No. 2016 GXNSFBA380022).
文摘Background Nicorandil (NIC) is a vasodilatory drug used to treat angina. However, its efficacy of cardioprotection in coronary mi- croembolization (CME) is largely unknown. This study was undertaken to determine whether nicorandil pretreatment could attenuate myo- cardial apoptosis and improve cardiac function after CME in rats. Methods Forty-five rats were randomly divided into a Sham group, a CME group and a CME + NIC (NIC) group (n = 15 per group). CME was established by injecting plastic microspheres (42 pm in diameter) into the left ventricle of the rats in all of the groups except the Sham group. The NIC group received nicorandil at 3 mg/kg per day for seven days before the operation. Cardiac fimction was assessed by echocardiography, the expression levels of cleaved caspase-9/8/3 were detected by Western blot, microinfarction area was measured by haematoxylin-basic fuchsin picric acid staining, and myocardial apoptosis was de- tected by TUNEL staining. Results Compared to that in the Sham group, cardiac fimction in the CME group was significantly decreased (P 〈 0.05). However, compared to the CME group, the NIC group showed improved cardiac function (P 〈 0.05). The expression levels of cleaved caspase-9/8/3 protein and myocardial apoptosis were dramatically increased in the CME group compared to those in the Sham group (P 〈 0.05), while the NIC pretreatment group had significantly decreased expression levels of cleaved caspase-9/8/3 protein as well as a de- creased apoptotic rate (P 〈 0.05). Conclusions NIC pretreatment inhibited CME-induced myocardial apoptosis and improved cardiac func- tion through blockade of the mitochondrial and death receptor-mediated apoptotic pathways.
基金supported by the National Key Research and Development program of China(2018ZX09201013)Xinxin Merck Cardiovascular Research Fund(2017-CCA-xinxin merck fund-003)。
文摘Previous studies have shown that nicorandil has a protective effect on cardiomyocytes.However,there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct size in patients with ST-segment elevation myocardial infarction(STEMI)compared to the current standard of percutaneous coronary intervention(PCI)regimen.The CHANGE(China-Administration of Nicorandil Group)study is a multicenter,prospective,randomized,double-blind and parallel-controlled clinical study of STEMI patients undergoing primary PCI in China,aiming to evaluate the efficacy and safety of intravenous nicorandil in ameliorating the myocardial infarct size in STEMI patients undergoing primary PCI and provide evidence-based support for myocardial protection strategies of STEMI patients.
基金supported by a grant from the Shanghai Clinical Medical Center of organ transplantation(QY040101-2-04)
文摘BACKGROUND:Neurological injury is a common complication in the early period after liver transplantation,posing an enormous obstacle to treatment efficiency and patient survival.Nicorandil is a mitochondrial ATP-sensitive potassium channel(mitoK ATP) opener.It has been reported to be effective in reducing brain injury in recent studies.However,it is still unclear whether nicorandil has cerebral protective effect in patients undergoing liver transplantation.METHODS:Fifty patients scheduled for liver transplantation were randomly divided into a nicorandil group(group N)(n=25),in which patients received 10 mg nicorandil through a nasogastric tube 30 minutes before induction of anesthesia,and a control group(group C)(n=25) who received 10 mL normal saline.The Mini-Mental State Examination(MMSE) was performed before anesthesia(day 0),and on days 3 and 7 after surgery.Blood samples were obtained before induction of anesthesia(T1),and at 12(T2) and 36 hours(T3) after surgery for determination of serum neuron-specific enolase(NSE) and S100β protein(S100β) concentrations.RESULTS:During surgery,5 patients in each group were eliminated due to severe reperfusion or renal insufficiency.Therefore,20 patients remained in each group.The MMSE scores after operation were significantly lower than those before operation in group C.However,there was no difference at days 3 and 7 compared with day 0 in group N.Serum NSE concentrations after surgery were significantly higher than baseline(at T1) in both groups,except at T3 in group N.Serum S100β concentration after surgery was significantly higher than baseline(at T1) in both groups.The MMSE scores at days 3 and 7 in group N were significantly higher than those in group C.The concentrations of serum NSE and S100β at T2 and T3 in group N were significantly lower than those in group C.CONCLUSIONS:Oral nicorandil,as a premedication before liver transplantation,improves postoperative MMSE scores.It also attenuates the increase of NSE and S100β in blood,indicating its cerebral protective effect.
基金supported by the National Natural Science Foundation of China(No.20445002)the Science Foundation of Shannxi province(No.2005B27).
文摘A rapid and sensitive HPLC-DAD method is developed for simultaneous determination of nicorandil and its degradation products, N-(2-hydroxyethyl) nicotinamide, nitrate ion and nicotinic acid, using nicotinamide (NT) as internal standard, at wavelength 204 nm. Nicotinic acid is identified by HPLC and GC/MS. The method can also be applied to study kinetic of degradation processes of nicorandil in storage.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Korean Ministry of Education,Science and Technology(NRF-2012R1A1A1013210)by a grant of the Korean Health Technology R&D Project,Ministry of Health,Welfare&Family Affairs,Republic of Korea(A092018).
文摘The aim of this study was to design and evaluate extended-release formulations of a model drug,nicorandil,in order to achieve the desired steady-state plasma concentration of drug in vivo.Simulation was employed to estimate optimum dissolution and absorption rate of nicorandil.The dissolution test was employed using pH 1.2,4.0,6.8 buffer solution,or water,to measure the in vitro release behaviors of nicorandil formulations.A single dose(15 mg)of each formulation was orally administered to four beagle dogs under fasted conditions,and the pharmacokinetic parameters were calculated.The in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle dogs.Nicorandil was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release tablets.The nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release formulation.The release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extendedrelease formulations.These results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.
基金This work was supported by the National Natural Science Foundation of China(31771058,32071359,11421202,61227902 and 11120101001)NationalKey Technology R&D Program(2016YFC1100704,2016YFC1101101)+3 种基金International Joint Research Center of Aerospace Biotechnology and Medical Engineering from Ministry of Science and Technology of China111 Project(B13003)Research Fund for the Doctoral Program of Higher Education of China(20131102130004)Fundamental Research Funds for the Central Universities.
文摘For the surgical treatment of cardiovascular disease(CVD),there is a clear and unmet need in developing small-diameter(diameter<6 mm)vascular grafts.In our previous work,sulfated silk fibroin(SF)was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility.However,vascular graft with single layer is difficult to adapt to the complex internal environment.In this work,polycaprolactone(PCL)and sulfated SF were used to fabricate bilayer vascular graft(BLVG)to mimic the structure of natural blood vessels.To enhance the biological activity of BLVG,nicorandil(NIC),an FDA-approved drug with multi-bioactivity,was loaded in the BLVG to fabricate NIC-loaded BLVG.The morphology,chemical composition and mechanical properties of NIC-loaded BLVG were assessed.The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior.The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation,migration and antioxidation capability of endothelial cells(ECs).Moreover,we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway.Overall,the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.
文摘Background: Reduction of myocardial reperfusion injury during cardiopulmonary bypass is an essential requirement for increasing the success rate, decreasing morbidity and mortality of open-heart surgery. Aim: To study the role of pre-operative oral nicorandil in decreasing reperfusion cardiac injury in patients subjected to cardiac valve surgery. Patients and Methods: The study included 62 patients, who were equally randomized into two groups: nicorandil group and control group. Pre-operative, intra-operative and post- operative data were reported and analyzed. Left Ventricle Ejection Fraction (LVEF) was estimated pre-operatively and postoperatively for both groups. Troponin I, creatine kinase-muscle/brain (CK-MB), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured before surgery by 24 hours then 4, 12 and 48 hours after aortic cross clamp removal. Results: Nicorandil considerably decreased TNF-α and IL-6 after 4 and 12 hours following the removal of aortic clamping. It also reduced troponin-I and CKMB at the same time points. However, there were no important changes in IL-6, TNF-α, troponin-I and CK-MB levels in control group in comparison to nicorandil group in the next 48 hours following the removal of aortic clamping. Conclusions: Pre-operative oral nicorandil expressively decreased myocardial reperfusion damage during open heart valve operations, this evidenced by the decrease in the postoperative use of inotropic drugs, considerable reduction of postoperative elevation of cardiac enzymes and inflammatory cytokines with no reported complications.
基金supported by research grants from the Natural Science Foundation of Shandong Province[grant number ZR2017BH114],the National Natural Science Foundation of China[grant number 81700334],and Jinan Science and Technology Plan Project[grant number 201805058].
文摘Aim:The effects of tirofiban combined with nicorandil on effective reperfusion,and the levels of interleukin-4(IL-4)and soluble intercellular adhesion molecule-1(sICAM-1)after percutaneous coronary intervention(PCI)for chronic coronary total occlusion(CTO)were investigated.Method:From January 1,2017,to June 31,2019,a total of 40 patients with CTO receiving PCI in Shandong Qian-foshan Hospital were randomly divided into a control group(treated with single tirofiban)and a cocktail group(treated with nicorandil combined with tirofiban).Effective reperfusion was compared between groups.In addition,differences in coronary serum IL-4 and sICAM-1 levels before and 10 min after the operation were compared between groups,and the incidence rates of adverse reactions were observed.Finally,patient follow-up occurred at 1 month and 6 months,and the total incidence rates of adverse cardiac events in both groups were assessed.Results:The levels of IL-4 and sICAM-1 in the cocktail group significantly decreased after the operation(P<0.05).In addition,after the operation,significantly greater decreases in the IL-4 and sICAM-1 levels were observed in the cocktail group than the control group(P<0.05).The Seattle Angina Scale(SAQ)score of the cocktail group,compared with the control group,showed a significant improvement after vessel opening in the patients with CTO.At the 1-month follow-up,the SAQ score of the cocktail group,compared with the control group,indicated further improvements in terms of angina attack frequency.No significant differences were observed in the incidence rates of adverse reactions between groups(P>0.05).Conclusion:The treatment of patients with CTO undergoing PCI with nicorandil and tirofiban alleviated the inflam-matory response,improved the SAQ scores,and decreased the occurrence of angina pectoris in patients.Moreover,this treatment is safe and reliable,and has important clinical significance.
文摘Objective:To study the effect of nicorandil on postoperative myocardial injury, platelet function and inflammatory response in patients with slow reflow in PCI.Methods: Patients who underwent emergency PCI and had intraoperative slow reflow in Zigong Fourth People's Hospital between March 2015 and August 2017 were selected and divided into nicorandil group and normal control group according to the application of nicorandil after no reflow or not in the history data. The levels of myocardial injury indexes in serum as well as the expression of platelet activation molecules and inflammatory signaling molecules in peripheral blood were measured before PCI as well as 1 day and 3 days after PCI.Results: Compared with the corresponding indexes of same group before PCI, serum H-FABP, HIF-1α, CK-MB and cTnⅠlevels as well as peripheral blood PAR1, PAR4, CCR2, p38MAPK, HSP27, Notch1, NF-κB, MEK1, ERK1/2 and CaMKⅡ mRNA expression of both groups of patients were significantly lower 1 day and 3 days after PCI, and serum H-FABP, HIF-1α, CK-MB and cTnⅠ levels as well as peripheral blood PAR1, PAR4, CCR2, p38MAPK, HSP27, Notch1, NF-κB, MEK1, ERK1/2 and CaMKII mRNA expression of nicorandil group 1 day and 3 days after PCI were significantly lower than those of normal control group.Conclusions:Nicorandil has negative regulating effect on postoperative myocardial injury, platelet activation and inflammatory response activation in patients with slow reflow in PCI.
文摘Objective:To study the effect of adjuvant nicorandil therapy on inflammation, plaque stability and platelet function in patients with unstable angina.Methods:A total of 134 patients with unstable angina who received drug therapy in our hospital between March 2015 and March 2016 were selected as the research subjects and randomly divided into the experimental group who accepted nicorandil combined with conventional therapy and the control group who accepted conventional therapy. 2 weeks after treatment, serum inflammation indexes and plaque stability indexes as well as peripheral blood platelet function parameters were determined.Results:2 weeks after treatment, serum hs-CRP, TNF-α, IL-18, IL-23, MMP1, MMP2, MMP3, MMP9 and ICTP levels of experimental group were significantly lower than those of control group;peripheral blood CD63, PAC-1, CD42b and GP-VI fluorescence intensity as well as Angle, MA and CI levels of experimental group were significantly lower than those of control group while R and K levels were significantly higher than those of control group.Conclusion:Adjuvant nicorandil therapy can relieve the inflammatory response in patients with unstable angina, and thereby inhibit the inflammation-mediated fibrous cap degradation, plaque stability decrease, platelet activation and thrombosis.
文摘Objective:To explore the effect of nicorandil on the coronary artery microcirculation and hemodynamics in patients with coronary slow flow (CSF).Methods: A total of 86 patients with CSF who were admitted in our hospital were included in the study and randomized into the treatment group and the control group with 43 cases in each group. The patients in the control group were given aspirin, HMG-CoA reductase inhibitor, and ACEI. On this basis, the patients in the treatment group were given nicorandil. The patients in the two groups were continuously treated for 6 months. The coronary artery microcirculation and hemodynamic indicators before and after treatment in the two groups were detected and compared.Results:TAT, ET-1, and hs-CRP levels, LAD, LCX, RCA, TIMI average blood flow frame count value, and IMR after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05). The above indicators after treatment in the treatment group were significantly lower than those in the control group (P<0.05). FMD after treatment in the two groups was significantly elevated when compared with before treatment (P<0.05). FMD after treatment in the treatment group was significantly higher than that in the control group (P<0.05). Conclusions: Nicorandil in the treatment of CSF can effectively improve the coronary artery microcirculation and hemodynamics, with a significant efficacy.
文摘Objective: To observe the influence of nicorandil combined with creatine phosphate sodium on serum BNP, CK-MB, cTnl, SOD, MMP-9 and cardiac function in patients with STEMI. Methods: A total of 60 patients with STEMI were randomly divided into observation group (30 cases) and control group (30 cases). Observation group: nicorandil combined with creatine phosphate sodium;control group: patients were treated only by nicorandil. Recording and comparing the levels of BNP, CK-MB, cTnl, SOD, MMP-9 and cardiac function before and after treatment. Results: (1) Before treatment, there was no statistically significant difference in the serum BNP, CK-MB, cTnl, SOD, MMP-9 levels between the two groups. After treatment, compared with the same group before treatment, the serum BNP, CK-MB, cTnl, MMP-9 levels of the two groups were significantly lower, the serum SOD level of the two groups were significantly higher, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups. (2) Before treatment, there was no statistically significant difference in LVEF, WMSI, CI between the two groups. After treatment, compared with the same group before treatment, the WMSI of the two groups were significantly lower, the LVEF and CI of the two groups were significantly higher, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups. Conclusion: Nicorandil combined with creatine phosphate sodium for patients with STEMI can perfect the levels of serum BNP, CK-MB, cTnl, SOD, MMP-9 and be beneficial to protect their cardiac function.
文摘Objective::Residual cardiovascular risk in patients with coronary heart disease(CHD)still needs to be addressed in real-world practice.This study aimed to examine the clinical effectiveness of nicorandil and nitrate in addition to optimal treatment for CHD patients.Methods::This retrospective cohort study included patients with CHD between October 2009 and March 2020 from 2 tertiary hospitals in Wuhan,China.Patients were grouped into nicorandil and nitrate groups depending on the first recorded antianginal therapy.Demographic and clinical data were collected from databases of the 2 hospitals.The primary outcome was cumulative 18-month major adverse cardiovascular event(MACE)-free survival,which was evaluated by Kaplan-Meier analysis.Propensity score matching(PSM)and multivariate Cox regression were adopted to adjust for confounding factors.Results::A total of 14,275 patients were analyzed,including 590 and 13,685 patients in the nicorandil and nitrate groups,respectively.With a median follow-up of 0.88(Q1,Q3:0.21,1.54)years,the cumulative 18-month MACE-free survival rates were comparable between the 2 groups(80.0%vs.75.0%,adjusted hazard ratio(aHR):1.04,95%confidence interval(CI):0.42-2.56,P=0.982,7)after 1:4 PSM.The cumulative 18-month stroke-free survival rate was significantly higher in the nicorandil group compared to the nitrate group(93.0%vs.84.0%,aHR:0.56,95%CI:0.34-0.92,P=0.023,5).Conclusion::This retrospective study showed that nicorandil and nitrate have similar 18-month rates of MACEs in CHD patients,but nicorandil is associated with lower incidence of stroke compared to nitrate.More studies need to be conducted to validate this association and explore the long-term benefit of nicorandil use on the occurrence of MACEs in the future.