格列本脲对急性心肌梗死合并2型糖尿病患者PCI术后心肌不良效应的研究
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摘要
目的:本文通过对比规律服用格列本脲和规律应用胰岛素或单纯饮食控制血糖的急性心肌梗死合并2型糖尿病患者心肌灌注情况及心律失常发生率,探讨格列苯脲可能对缺血心肌的不良效应,为更有效、更合理的治疗提供依据。
方法:选择2008年2月至2009年12月于我科住院的冠心病急性心肌梗死合并2型糖尿病患者105例(男性60例,女性45例,平均年龄56.87±8.95岁)。所有患者符合WHO冠心病急性心肌梗死的诊断标准;符合WHO 2型糖尿病的诊断标准;依从性好能定期随访。排除标准:胰岛素依赖的糖尿病患者;原有严重瓣膜性心脏病,心肌病,心肌炎,心包炎,原发肺动脉高压者;明确诊断患有糖尿病性视网膜增值性病变患者;患有糖尿病神经病变及糖尿病肾病的患者(血肌酐>136μmol/L);潜在的胃肠道出血、贫血、合并其他内分泌疾病或主要脏器疾病如严重肝肾功能不全者,恶性肿瘤患者。
将105名入选患者根据既往治疗情况分为规律应用格列苯脲为试验组A组35例,应用胰岛素为对照组B组35例,饮食控制为空白对照组C组35例。所有患者入院后基础治疗均接受标准的抗血小板、抗凝治疗,皮下注射低分子肝素,并同时服用肠溶阿司匹林,氯吡格雷,血管紧张素转换酶抑制剂(ACEI)、他汀类调脂药物、硝酸酯类药物,酌情选用选择性β1受体阻滞剂,继续维持以往降糖治疗,A组应用格列苯脲(2.5mg-5mg,3/日,天津太平洋制药有限公司);B组应用生物合成人胰岛素(诺和公司,25u-50u/日);C组单纯饮食控制。每组患者收集详细临床资料,年龄、性别、体重指数、吸烟、饮酒、高血压、血脂、行心电图、心肌酶、肌钙蛋白I、肝肾功能、血常规、尿便常规、血脂、血糖、糖化血红蛋白、胰岛素及C肽释放、24小时尿白蛋白排泄率等、心功能分级,患者入院后七日行心脏超声明确心功能;全部患者择期行冠状动脉造影明确冠脉情况,并行冠状动脉支架植入术(PCI),记录冠状动脉造影血管病变支数、病变程度、TIMI分级、支架类型等。三组患者均于术后3-5天内行动态心电图检查。稳定后出院,并于术后一个月复查,行单光子发射型计算机心肌断层显像(简称SPECT),观察心肌缺血面积,平衡门控心血池显像(equilibrium radionuclide angiography,ERNA)观察左心室射血分数;所有数据均应用SPSS13.0软件包进行统计学处理,正态计量资料以均数±标准差表示,非正态计量资料用中位数表示,正态计量资料采用t检验,计量资料多组间比较采用方差分析,计数资料采用χ~2检验,等级资料及非正态计量资料采用秩和检验,以P<0.05定为有统计学意义。
结果:两组患者在性别、体重指数、吸烟、饮酒、高血压、服用药物、血常规、血脂、糖化血红蛋白、血糖、胰岛素、C-肽、肾功能、尿蛋白、心功能分级、冠脉造影病变情况、支架类型等方面比较无统计学差异。冠脉造影结果显示三组患者TIMI血流 Holter结果显示,格列苯脲组室性心律失常发生率低于两对照组,差异有统计学意义,(22.86% vs 48.57% vs 51.54%,χ~2=8.810, P=0.012),两两比较A组发生率低于B组,差异有统计学意义(χ~2=6.341, P=0.012);A组发生率低于C组,差异有统计学意义(χ~2 = 7.529, P=0.006);B组发生率低于C组,差异无统计学意义(χ~2=0.057, P=0.881)。心律失常评分,格列苯脲组评分低于两对照组,差异有统计学意义(10 vs 25 vs 23,χ~2=7.410, P=0.025);其中A组评分低于B组,差异有统计学意义(χ~2=6.991, P=0.008;A组评分低于C组,差异有统计学意义(χ~2=5.915, P=0.015);B组、C组差异无统计学意义(χ~2=0.195, P=0.659)。
静息状态下格列苯脲组患者出现缺血心肌节段高于两对照组,差异有统计学意义(380 vs 300 vs 302,χ~2=11.396, P=0.003),其中A组缺血心肌节段高于B组,差异有统计学意义(χ~2=6.138, P=0.013);A组缺血心肌节段高于C组,差异有统计学意义(χ~2=11.221, P=0.001);B组、C组差异无统计学意义(χ~2=0.008, P=0.929 )。静息无硝甘介入时格列苯脲组心肌~(99m)Tc-MIBI摄取率低于两对照组,差异有统计学意义[48.35% vs(55.20±7.19)% vs 54.34%,χ~2=15.268, P=0.000];两两比较,A组心肌~(99m)Tc-MIBI摄取率低于B组,差异有统计学意义(χ~2=12.668, P=0.000);A组心肌~(99m)Tc-MIBI摄取率低于C组,差异有统计学意义(χ~2=9.042, P=0.003);B组、C组差异无统计学意义(χ~2=1.871, P=0.277);硝酸甘油介入后格列苯脲组~(99m)Tc-MIBI摄取率低于两对照组,差异有统计学意义(56.17% vs 65.7% vs 62.17%,χ~2=11.627, P=0.003),两两比较A组心肌~(99m)Tc-MIBI摄取率低于B组,差异有统计学意义(χ~2=9.544, P=0.002);A组心肌~(99m)Tc-MIBI摄取率低于C组,差异有统计学意义(χ~2=6.648, P=0.010);B组、C组差异无统计学意义(χ~2=1.298, P=0.255)。A组硝酸甘油介入前~(99m)Tc-MIBI摄取率低于硝酸甘油介入后,差异有统计学意义(48.35% vs 56.17%,χ~2=5.159, P=0.000);B组硝酸甘油介入前~(99m)Tc-MIBI摄取率低于硝酸甘油介入后,差异有统计学意义[(55.20±7.19)% vs 65.7%,χ~2=24.377, P=0.000];C组硝酸甘油介入前~(99m)Tc-MIBI摄取率低于硝酸甘油介入后,差异有统计学意义(54.34% vs 62.17%,χ~2=22.355, P=0.000)。格列苯脲组心肌缺血面积评分高于两对照组,差异有统计学意义(64 vs 46 vs 46,χ~2=8.538, P=0.014<0.05),其中A组心肌缺血面积评分高于B组,差异有统计学意义(χ~2=5.873, P=0.015<0.017);A组心肌缺血面积评分高于C组,差异有统计学意义(χ~2=6.768, P=0.009<0.017);B组、C组差异无统计学意义(P=0.969>0.05)。ERNA显示格列苯脲组左室射血分数低于两对照组,差异有统计学意义[53% v(s56.51±4.23)% vs 60%,χ~2=21.479, P=0.000<0.05];A组左室射血分数低于B组,差异有统计学意义(P=0.001<0.017);A组左室射血分数低于C组,差异有统计学意义(χ~2=4.545, P=0.000<0.017 ); B组、C组差异无统计学意义(P=0.033>0.017)。
结论:1应用格列苯脲组患者心肌显像缺血面积高于胰岛素及饮食控制组,提示格列苯脲会增加急性心肌梗死合并2型糖尿病患者心肌缺血或梗死面积,并减低左心室收缩功能。
2格列苯脲影响急性心肌梗死合并2型糖尿病的患者冠脉的TIMI血流。
3格列苯脲对急性心肌梗死合并2型糖尿病的患者减少发生恶性心律失常的可能。
Objective: To compare the myocardial perfusion conditions and the incidence of arrhythmias in patients with CHD and type 2 diabetes who taking glibenclamide or insulin regularly, to assess the adverse effects of glibenclamide on the myocardium, for investigating more effective and rational therapy.
Methods: From June, 2008 and December, 2009, 105 consecutive patients (60 male and 45female, age 56.87±8.95 years) who with type 2 diabetes and coronary artery disease were enrolled into the study. All patients had clinical histories of acute myocardial infarction and losed the chance of thrombolysis and emergency PCI; Type 2 Diabetes were diagnosed according to the criterion of WHO; Patients were excluded for any of the following reasons: Insulin-dependent diabetes mellitus; The original severe valvular heart disease, cardiomyopathy, myocarditis, pericarditis, primary pulmonary hypertension; diabetic proliferative retinopathy assessed by an experienced ophthalmologist; diabetic neuropathy assessed by autonomic neuropathy tests or diabetic nephropathy (creatinine>136μmol/L); potential of gastrointestinal bleeding, anemias, and other endocrine or major organ diseases.
Each patient was assigned to either insulin or glibenclamide group according to which treatment he accepted outside hospital regularly. The patients who took glibenclamide for group A, insulin for group B and diet for group C. All patients were admitted to hospital and subcutaneous inject low molecula heparin, while oral aspirin, clopidogrel, angiotensin-converting enzyme inhibitor (ACEI), statins, nitrates, If necessary, applied appropriate dose ofβ1-blockers. Collected the clinical informations of all patients in each group detailed, age, sex, body mass index, smoking, drinking, hypertension, hyperlipidemia, electrocardiogram, myocardial enzymes, cardiac troponin I, liver and kidney function, red cell, urine will be normal, blood lipids, blood glucose, glycated hemoglobin, insulin and C-peptide release, a 24-hour urinary albumin excretion, 7 days after myocardial infarction all patients took echocardiography to evaluate the condition of wall motion, ventricular wall thickness, ventricular diameter; 10 days after took selective coronary angiography and PCI, recorded the TIMI rank of the coronary flow lesion count, lesion extent, stents types, etc, took holter in the 3-5 days after operation. one month after PCI all patients took SPECT to evaluate the condition of myocardial perfusion, and ERNA for LVEF; All data are applied SPSS 13.0 for statistical analysis, Normal measurement data express to mean±standard deviation, multiple independent groups was used ANOVA, enumeration data and ranked data usingχ~2 test, with P<0.05 as statistically significant.
Results: The three groups in gender, body mass index, smoking, drinking, high blood pressure, blood lipids, glycated hemoglobin, blood glucose, insulin, C-peptide, kidney function, medication, coronary angiography lesions, stents types, etc. connection was no statistical difference. The results of coronary angiography showed that the ratio of the patients with0.05). The results of Holter showed that the incidence of arrhythmia of the three groups were significantly difference(22.86% vs 48.57% vs 51.54%,χ~2=8.810, P=0.012<0.05), A and B group differences were statistically significant (22.86% vs 48.57%,χ~2=6.341, P=0.012<0.05); A group, C group differences were statistically significant (22.86% vs 51.54%,χ~2 =7.529, P=0.006<0.017), B group, C group no statistically significant difference (48.57% vs 51.54%,χ~2=0.057, P=0.881>0.05). The arrhythmia scores were statistically significant differences between the three groups (10 vs 25 vs 23,χ~2=7.410, P=0.025<0.05), where A, B group the differences were statistically significant (10 vs 25,χ~2=6.991, P=0.008 <0.017), A group, C group differences were statistically significant (10 vs 23,χ~2=5.915, P=0.015<0.017), B group, C group were not statistically significant difference (25 vs 23,χ~2=0.195, P=0.659>0.017). ECT results showed that In the rest state, the ratio of abnormal myocardial perfusion segments in the three groups were statistically significant difference (32.90% vs 25.97% vs 26.15%, P=0.003<0.05); where A, B group were statistically significant difference (32.90% vs 25.97%, P=0.013<0.017); A group, C group were statistically significant difference (32.90% vs 26.15%, p P=0.001<0.017); B group, C group were not statistically significant difference (25.97% vs 26.15%, P= 0.929>0.05); The ischemic myocardial area score A group was significantly higher than B group and C group (380 vs 300, P=0.013<0.017 ), (380vs302, P =0.001<0.017); B group and C group were no significant difference (300 vs 302, P=0.929>0.017). ERNA showed that LVEF in the three groups were statistically significant difference (53%vs(56.51±4.23)% vs 60%,χ~2 =21.479, P=0.000<0.05), A group was significantly lower than B group [53% vs (56.51±4.23)%, P=0.001<0.017]; there were no significant difference between B group and C group [(56.51±4.23)% vs 60%, P=0.033>0.017], A group, C group differences were statistically significant (53% vs 60%,χ~2=4.545, P=0.000<0.017), illustrated the LVEF of A group was significantly lower than B group and C group.
Conclusion: 1. The ischemic areas of myocardial perfusion imaging of the patients who had long histories of application of glibenclamide was higher than those of the insulin and diet groups, suggesting that glibenclamide would increase myocardial ischemic area in patients with acute myocardial infarction and type 2 diabetes mellitus, And it would decrease the LVEF severely.
2. Glibenclamide had significant adverse effects on TIMI grade of the coronary flow in the patients with acute myocardial infarction and type 2 diabetes mellitus.
3. Glibenclamide increases the possibility of malignant arrhythmias in the patients with acute myocardial infarction and type 2 diabetes mellitus.
方法:选择2008年2月至2009年12月于我科住院的冠心病急性心肌梗死合并2型糖尿病患者105例(男性60例,女性45例,平均年龄56.87±8.95岁)。所有患者符合WHO冠心病急性心肌梗死的诊断标准;符合WHO 2型糖尿病的诊断标准;依从性好能定期随访。排除标准:胰岛素依赖的糖尿病患者;原有严重瓣膜性心脏病,心肌病,心肌炎,心包炎,原发肺动脉高压者;明确诊断患有糖尿病性视网膜增值性病变患者;患有糖尿病神经病变及糖尿病肾病的患者(血肌酐>136μmol/L);潜在的胃肠道出血、贫血、合并其他内分泌疾病或主要脏器疾病如严重肝肾功能不全者,恶性肿瘤患者。
将105名入选患者根据既往治疗情况分为规律应用格列苯脲为试验组A组35例,应用胰岛素为对照组B组35例,饮食控制为空白对照组C组35例。所有患者入院后基础治疗均接受标准的抗血小板、抗凝治疗,皮下注射低分子肝素,并同时服用肠溶阿司匹林,氯吡格雷,血管紧张素转换酶抑制剂(ACEI)、他汀类调脂药物、硝酸酯类药物,酌情选用选择性β1受体阻滞剂,继续维持以往降糖治疗,A组应用格列苯脲(2.5mg-5mg,3/日,天津太平洋制药有限公司);B组应用生物合成人胰岛素(诺和公司,25u-50u/日);C组单纯饮食控制。每组患者收集详细临床资料,年龄、性别、体重指数、吸烟、饮酒、高血压、血脂、行心电图、心肌酶、肌钙蛋白I、肝肾功能、血常规、尿便常规、血脂、血糖、糖化血红蛋白、胰岛素及C肽释放、24小时尿白蛋白排泄率等、心功能分级,患者入院后七日行心脏超声明确心功能;全部患者择期行冠状动脉造影明确冠脉情况,并行冠状动脉支架植入术(PCI),记录冠状动脉造影血管病变支数、病变程度、TIMI分级、支架类型等。三组患者均于术后3-5天内行动态心电图检查。稳定后出院,并于术后一个月复查,行单光子发射型计算机心肌断层显像(简称SPECT),观察心肌缺血面积,平衡门控心血池显像(equilibrium radionuclide angiography,ERNA)观察左心室射血分数;所有数据均应用SPSS13.0软件包进行统计学处理,正态计量资料以均数±标准差表示,非正态计量资料用中位数表示,正态计量资料采用t检验,计量资料多组间比较采用方差分析,计数资料采用χ~2检验,等级资料及非正态计量资料采用秩和检验,以P<0.05定为有统计学意义。
结果:两组患者在性别、体重指数、吸烟、饮酒、高血压、服用药物、血常规、血脂、糖化血红蛋白、血糖、胰岛素、C-肽、肾功能、尿蛋白、心功能分级、冠脉造影病变情况、支架类型等方面比较无统计学差异。冠脉造影结果显示三组患者TIMI血流
静息状态下格列苯脲组患者出现缺血心肌节段高于两对照组,差异有统计学意义(380 vs 300 vs 302,χ~2=11.396, P=0.003),其中A组缺血心肌节段高于B组,差异有统计学意义(χ~2=6.138, P=0.013);A组缺血心肌节段高于C组,差异有统计学意义(χ~2=11.221, P=0.001);B组、C组差异无统计学意义(χ~2=0.008, P=0.929 )。静息无硝甘介入时格列苯脲组心肌~(99m)Tc-MIBI摄取率低于两对照组,差异有统计学意义[48.35% vs(55.20±7.19)% vs 54.34%,χ~2=15.268, P=0.000];两两比较,A组心肌~(99m)Tc-MIBI摄取率低于B组,差异有统计学意义(χ~2=12.668, P=0.000);A组心肌~(99m)Tc-MIBI摄取率低于C组,差异有统计学意义(χ~2=9.042, P=0.003);B组、C组差异无统计学意义(χ~2=1.871, P=0.277);硝酸甘油介入后格列苯脲组~(99m)Tc-MIBI摄取率低于两对照组,差异有统计学意义(56.17% vs 65.7% vs 62.17%,χ~2=11.627, P=0.003),两两比较A组心肌~(99m)Tc-MIBI摄取率低于B组,差异有统计学意义(χ~2=9.544, P=0.002);A组心肌~(99m)Tc-MIBI摄取率低于C组,差异有统计学意义(χ~2=6.648, P=0.010);B组、C组差异无统计学意义(χ~2=1.298, P=0.255)。A组硝酸甘油介入前~(99m)Tc-MIBI摄取率低于硝酸甘油介入后,差异有统计学意义(48.35% vs 56.17%,χ~2=5.159, P=0.000);B组硝酸甘油介入前~(99m)Tc-MIBI摄取率低于硝酸甘油介入后,差异有统计学意义[(55.20±7.19)% vs 65.7%,χ~2=24.377, P=0.000];C组硝酸甘油介入前~(99m)Tc-MIBI摄取率低于硝酸甘油介入后,差异有统计学意义(54.34% vs 62.17%,χ~2=22.355, P=0.000)。格列苯脲组心肌缺血面积评分高于两对照组,差异有统计学意义(64 vs 46 vs 46,χ~2=8.538, P=0.014<0.05),其中A组心肌缺血面积评分高于B组,差异有统计学意义(χ~2=5.873, P=0.015<0.017);A组心肌缺血面积评分高于C组,差异有统计学意义(χ~2=6.768, P=0.009<0.017);B组、C组差异无统计学意义(P=0.969>0.05)。ERNA显示格列苯脲组左室射血分数低于两对照组,差异有统计学意义[53% v(s56.51±4.23)% vs 60%,χ~2=21.479, P=0.000<0.05];A组左室射血分数低于B组,差异有统计学意义(P=0.001<0.017);A组左室射血分数低于C组,差异有统计学意义(χ~2=4.545, P=0.000<0.017 ); B组、C组差异无统计学意义(P=0.033>0.017)。
结论:1应用格列苯脲组患者心肌显像缺血面积高于胰岛素及饮食控制组,提示格列苯脲会增加急性心肌梗死合并2型糖尿病患者心肌缺血或梗死面积,并减低左心室收缩功能。
2格列苯脲影响急性心肌梗死合并2型糖尿病的患者冠脉的TIMI血流。
3格列苯脲对急性心肌梗死合并2型糖尿病的患者减少发生恶性心律失常的可能。
Objective: To compare the myocardial perfusion conditions and the incidence of arrhythmias in patients with CHD and type 2 diabetes who taking glibenclamide or insulin regularly, to assess the adverse effects of glibenclamide on the myocardium, for investigating more effective and rational therapy.
Methods: From June, 2008 and December, 2009, 105 consecutive patients (60 male and 45female, age 56.87±8.95 years) who with type 2 diabetes and coronary artery disease were enrolled into the study. All patients had clinical histories of acute myocardial infarction and losed the chance of thrombolysis and emergency PCI; Type 2 Diabetes were diagnosed according to the criterion of WHO; Patients were excluded for any of the following reasons: Insulin-dependent diabetes mellitus; The original severe valvular heart disease, cardiomyopathy, myocarditis, pericarditis, primary pulmonary hypertension; diabetic proliferative retinopathy assessed by an experienced ophthalmologist; diabetic neuropathy assessed by autonomic neuropathy tests or diabetic nephropathy (creatinine>136μmol/L); potential of gastrointestinal bleeding, anemias, and other endocrine or major organ diseases.
Each patient was assigned to either insulin or glibenclamide group according to which treatment he accepted outside hospital regularly. The patients who took glibenclamide for group A, insulin for group B and diet for group C. All patients were admitted to hospital and subcutaneous inject low molecula heparin, while oral aspirin, clopidogrel, angiotensin-converting enzyme inhibitor (ACEI), statins, nitrates, If necessary, applied appropriate dose ofβ1-blockers. Collected the clinical informations of all patients in each group detailed, age, sex, body mass index, smoking, drinking, hypertension, hyperlipidemia, electrocardiogram, myocardial enzymes, cardiac troponin I, liver and kidney function, red cell, urine will be normal, blood lipids, blood glucose, glycated hemoglobin, insulin and C-peptide release, a 24-hour urinary albumin excretion, 7 days after myocardial infarction all patients took echocardiography to evaluate the condition of wall motion, ventricular wall thickness, ventricular diameter; 10 days after took selective coronary angiography and PCI, recorded the TIMI rank of the coronary flow lesion count, lesion extent, stents types, etc, took holter in the 3-5 days after operation. one month after PCI all patients took SPECT to evaluate the condition of myocardial perfusion, and ERNA for LVEF; All data are applied SPSS 13.0 for statistical analysis, Normal measurement data express to mean±standard deviation, multiple independent groups was used ANOVA, enumeration data and ranked data usingχ~2 test, with P<0.05 as statistically significant.
Results: The three groups in gender, body mass index, smoking, drinking, high blood pressure, blood lipids, glycated hemoglobin, blood glucose, insulin, C-peptide, kidney function, medication, coronary angiography lesions, stents types, etc. connection was no statistical difference. The results of coronary angiography showed that the ratio of the patients with
Conclusion: 1. The ischemic areas of myocardial perfusion imaging of the patients who had long histories of application of glibenclamide was higher than those of the insulin and diet groups, suggesting that glibenclamide would increase myocardial ischemic area in patients with acute myocardial infarction and type 2 diabetes mellitus, And it would decrease the LVEF severely.
2. Glibenclamide had significant adverse effects on TIMI grade of the coronary flow in the patients with acute myocardial infarction and type 2 diabetes mellitus.
3. Glibenclamide increases the possibility of malignant arrhythmias in the patients with acute myocardial infarction and type 2 diabetes mellitus.
引文
1 Gross GJ, Auchampach JA, et al Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs [J]. Circ Res, 1992, 70(2): 223-233
2 Grover G J, McCullough J R, Henry D E, et al. Anti-ischemic effects of the potassium channel activators pinacidil and cromakalim and the reversal of these effects with the potassium channel blocker[J]. J Pharmacol Exp Ther, 1989, 251 1: 98-104
3 Steenbergen C, Pefinan ME, London RE, et a1 Mechanism of preconditioning ionic alteration [J]. Circ Res, 1993, 72: 112-25
4 Tosaki A, rdis GA, acrdahelyi P, et al Effects of Preconditioning onReperfusion Arrhythmias, Myocardial Functions, Formation of Free Radicals, and Ion Shifts in Isolated Ischemic/Reperfused Rat Hearts [J].J Cardiovascular Pharmaco1ogy, 1994, 23: 365-367
5赵静,张凯伦,胡志伟等,二氮嗪预处理对大鼠心肌缺血-再灌注损伤的保护作用,中国胸心血管外科临床杂志[J],2005,12 04:270-273
6 Ashraf Hassouna, Mahmoud Loubani, et a1 Mitochondrial dysfunction as the cause of the failure to precondition the diabetic human myocardium. [J].Cardiovascular Research, 2006; 69: 450-458
7吴伟等,优降糖对K-ATP通道介导缺血预适应心肌再灌注损伤的影响,中国危重病急救医学,2002,14 10:609-611
8 Howes LG, Cardiovascular effects of sulphonylureas: role of K-ATP channels. Diabetes Obes Metab, 2000, 2: 67-73
9 Curtis MJ, Walker MJ. Quantification of arrhythmias using scoring systems: an examination of seven scores in an in vivo model of regional myocardial ischaemia. Cardiovasc Res, 1998, 22: 656-665
10 Lee T M, Chou T F. Impairment of myocardial protection in type 2 diabetic patient s [J]. J Clin Endocrinol Metab, 2003, 88: 531-537
11 Traverse J H, Chen Y, Hou M, et al Effect of K-ATP channel and adenosine receptor blockade during rest and exercise in congestive heart failure [J] .Circ Res, 2007, 100: 1643-1649
12 Kosmas EN, Levy RD, Hussain SNA. Acute effects of glyburide on the regulation of peripheral blood flow in normal humans. Eur J Pharmacol, 1995, 274: 193-199
13 Ascher T C. Boes U. Forearm vascular reactivity is differentially influenced by gliclazide and glibenclamide in chronically treated type 2 diabetic patients [J]. Clin Physiol Funct Imaging , 2005, 25: 40-46
14 Abbink E. J., Wollersheim H., Netten P. M., et al Microcirculatory effects of KATP channel blockade by sulphonylurea derivatives in humans, European Journal of Clinical Investigation, 2002, 3 32: 163-171
15 Ye Y, Lin Y, Perez-Polo JR, et al Oral glyburide, but not glimepiride, blocks the infarct-size limiting effects of pioglitazone. CardiovascularDrugs and Therapy, 2008, 22 6: 429-436
16 Tomai F, Crea F, Gaspardone A, et al Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATP-sensitive K+ channel blocKer. Circulation, 1994, 90: 700-705
17 Mori Minamiji K, Kurgan H, et al Rest-injected T1 imaging for assessing viability of severe asynergic regions J. Nucl Med, 1991, 32: 171
18 Calli M, Marcassa C, Silvap P, et al Improvement of resting 99mTc-sestamibi myocardial uptake by acute nitroglycerin administration[J]. J Am Coll Cardiol, 1993, 21 SupplA: 756
19 Roldano Scognamiglio, Angelo Avogaro, et al Effects of Treatment With Sulfonylurea Drugs or Insulinon Ischemia-Induced Myocardial Dysfunction in Type 2 Diabetes. DIABETES, 2002, 51: 808-812
20 Cacciapuoti F, Spiezia R, Bianchi U, et al Effectiveness of glibenclamide on myocardial ischemic ventricular arrhythmias in non-insulin-dependent diabetes mellitus. Am J Cardiol 1991, 67: 843-847
21 Lomuscio A, Vergani D, Marano L, et al. Effects of glibenclamide on ventricular fibrillation in non-insulin-dependent diabetics with acute myocardial infarction. Coron Artery Dis, 1994, 5: 767-771
1 Gibble FM, Ashcroft FM. Differential sensitivity of beta-cell and extrapancreatic K-ATP channels to gliclazide. Diabetologia, 1992, 42: 845-848
2 Lawrence CL, ProKs P, Rodrigo GC, et al Gliclazide produces high- affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells [J]. Diabetologia, 2001, 44 8: 1019-1025
3 Sakura H, Ammala C, Smith PA, et al Cloning and functional expression of the cDNA encoding a novel ATP - sensitive potassium channel subunit expressed in pancreatic beta-cells, brain, heart, and skeletal muscle[J]. FEBS Lett, 1995, 77 3: 338
4 Babenko AP, Aguilar Bryan L and Bryan J. A View of SUR/Kir6.X K-ATP channels [J ] . Annu Rev Physiol, 1998, 60: 667
5 Wang L, Cherednichenko G, Hernandez L, et al Preconditioning limits mitochondrial Ca2+ during ischemia in rat hearts: role of K-ATP channels. Am J Physiol Heart Circ Physiol, 2001, 280: H2321
6赵静,张凯伦,胡志伟等,二氮嗪预处理对大鼠心肌缺血-再灌注损伤的保护作用,中国胸心血管外科临床杂志[J],2005,12 04: 270-273.
7 Tilley Pain, Xi-Ming Yang, et al Opening of Mitochondrial K-ATP Channels Triggers the Preconditioned State by Generating Free Radicals. Circulation Research, 2000, 87: 460-466
8 Sasaki N, Sato T, Ohler A, et al Activation of mitochondrial ATP-dependent potassium channels by nitricoxide. Circulation, 2000, 101: 439–445
9 Yellon DM, Downey JM. Preconditioning the myocardium:from cellular physiology to clinical cardiology[J]. Physiol Rev, 2003, 83:1113-1151
10李寒等,二氮嗪对大鼠心肌缺血再灌注损伤的影响,中国体外循环杂志,2006,4 1:64
11 Billmen GE, Avendano GE, Hallliwill JR, et al The effects of theATP-dependent potassium channel antagonist, glyburide, on coronary blood flow and susceptibility to ventricular fibrillation in unanesthetized dogs. J Cardiovasc Pharmacol, 1993, 21: 197-204
12 TosaKi A, Szerdahelyi P, Engelman RM, et al J Pharmacol Exp Ther, 1995, 267: 1355-1362
13 Kosmas EN, Levy RD, Hussian SNA. Acute effects of glyburide on the regulation of peripheral blood flow in normal humans. Eur J Pharmacol, 1995, 274: 193-199
14 Wascher T C, Boes U. Forearm vascular reactivity is differentially influenced by gliclazide and glibenclamide in chronically treated type 2 diabetic patients [J]. Clin Physiol Funct Imaging , 2005, 25: 40-46
15 Reffelmann T, et al Post-stenotic coronary blood flow at rest is not altered by therapeutic doses of the oral antidiabetic drug glibenclamide in patients with coronary artery disease. Heart, 2002, 87 1: 57-60
16 ImamuraY, TomoikeH, Narishiget, et al Glibenclamide decreases basal coronary blood flow in anesthetized dogs, Am J Physiol, 1992, 263: 399-404
17 Roldano Scognamiglio, et al Effects of Treatment With Sulfonylurea Drugs or Insulin on Ischemia-Induced Myocardial Dysfunction in Type 2 Diabetes. Diabetes, 2002, 51 3: 808-812
18 McNulty PH, Pfau S, Deckelbaum LI, Effect of plasma insulin level on myocardial blood flow and its mechanism of action. Am J Cardiol, 2000, 85: 161–165
19 Enst T, Richwine RT, Bray MS, et al Insulin improves functional and metabolic recovery of reperfused working rat heart. Ann Thorac Surg, 1999, 67: 1682-1688
20 Abbink EJ, Pickkers P, Van Posendaol AJ, et al Vascular K-ATP channel blockade by glybenclamide, but not by acarbose, in patients with type 2 diabetes [J]. Clin Sci (Lond), 2002, 102 3: 307-314
21 Ohnson SP, Monster TBM, Olsen ML, et al Risk and short-term prognosis of myocardial infarction among users of antidiabetic drugs. AmericanJournal of Therapeutics, 2006, 13: 134-140
22 Fisman EZ, Tenenbaum A, Motro M, et al Oral antiabetic therapy in patients with heart disease. Herz, 2004, 29: 290-298
23 Schothorgh CE, Wilde AA. Sulfonylurea derivatives in cardiovascular research and in cardiovascular patients [J]. Cardiovasc Res, 1997, 34 1: 73-80
24 Halkin A, Roth A, Jonas M, et al Sulfonylureas are not associated with increased mortality in diabetics treated with thrombolysis for acute myocardial infraction [J]. J Thromb Thrombolysis, 2001, 12 2: 177-184
25 Hassouna A, Loubani M, Matata B M, et al Mitochondrial dysfunction as t he cause of t he failure to precondition the diabetic human myocardium [J]. CardiovascRes, 2006, 2: 450-458
26 Chan JC, Tomlinson B, Critchley JA et al Metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients. DiabetesCare, 1993, 16: 1035-1038
2 Grover G J, McCullough J R, Henry D E, et al. Anti-ischemic effects of the potassium channel activators pinacidil and cromakalim and the reversal of these effects with the potassium channel blocker[J]. J Pharmacol Exp Ther, 1989, 251 1: 98-104
3 Steenbergen C, Pefinan ME, London RE, et a1 Mechanism of preconditioning ionic alteration [J]. Circ Res, 1993, 72: 112-25
4 Tosaki A, rdis GA, acrdahelyi P, et al Effects of Preconditioning onReperfusion Arrhythmias, Myocardial Functions, Formation of Free Radicals, and Ion Shifts in Isolated Ischemic/Reperfused Rat Hearts [J].J Cardiovascular Pharmaco1ogy, 1994, 23: 365-367
5赵静,张凯伦,胡志伟等,二氮嗪预处理对大鼠心肌缺血-再灌注损伤的保护作用,中国胸心血管外科临床杂志[J],2005,12 04:270-273
6 Ashraf Hassouna, Mahmoud Loubani, et a1 Mitochondrial dysfunction as the cause of the failure to precondition the diabetic human myocardium. [J].Cardiovascular Research, 2006; 69: 450-458
7吴伟等,优降糖对K-ATP通道介导缺血预适应心肌再灌注损伤的影响,中国危重病急救医学,2002,14 10:609-611
8 Howes LG, Cardiovascular effects of sulphonylureas: role of K-ATP channels. Diabetes Obes Metab, 2000, 2: 67-73
9 Curtis MJ, Walker MJ. Quantification of arrhythmias using scoring systems: an examination of seven scores in an in vivo model of regional myocardial ischaemia. Cardiovasc Res, 1998, 22: 656-665
10 Lee T M, Chou T F. Impairment of myocardial protection in type 2 diabetic patient s [J]. J Clin Endocrinol Metab, 2003, 88: 531-537
11 Traverse J H, Chen Y, Hou M, et al Effect of K-ATP channel and adenosine receptor blockade during rest and exercise in congestive heart failure [J] .Circ Res, 2007, 100: 1643-1649
12 Kosmas EN, Levy RD, Hussain SNA. Acute effects of glyburide on the regulation of peripheral blood flow in normal humans. Eur J Pharmacol, 1995, 274: 193-199
13 Ascher T C. Boes U. Forearm vascular reactivity is differentially influenced by gliclazide and glibenclamide in chronically treated type 2 diabetic patients [J]. Clin Physiol Funct Imaging , 2005, 25: 40-46
14 Abbink E. J., Wollersheim H., Netten P. M., et al Microcirculatory effects of KATP channel blockade by sulphonylurea derivatives in humans, European Journal of Clinical Investigation, 2002, 3 32: 163-171
15 Ye Y, Lin Y, Perez-Polo JR, et al Oral glyburide, but not glimepiride, blocks the infarct-size limiting effects of pioglitazone. CardiovascularDrugs and Therapy, 2008, 22 6: 429-436
16 Tomai F, Crea F, Gaspardone A, et al Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATP-sensitive K+ channel blocKer. Circulation, 1994, 90: 700-705
17 Mori Minamiji K, Kurgan H, et al Rest-injected T1 imaging for assessing viability of severe asynergic regions J. Nucl Med, 1991, 32: 171
18 Calli M, Marcassa C, Silvap P, et al Improvement of resting 99mTc-sestamibi myocardial uptake by acute nitroglycerin administration[J]. J Am Coll Cardiol, 1993, 21 SupplA: 756
19 Roldano Scognamiglio, Angelo Avogaro, et al Effects of Treatment With Sulfonylurea Drugs or Insulinon Ischemia-Induced Myocardial Dysfunction in Type 2 Diabetes. DIABETES, 2002, 51: 808-812
20 Cacciapuoti F, Spiezia R, Bianchi U, et al Effectiveness of glibenclamide on myocardial ischemic ventricular arrhythmias in non-insulin-dependent diabetes mellitus. Am J Cardiol 1991, 67: 843-847
21 Lomuscio A, Vergani D, Marano L, et al. Effects of glibenclamide on ventricular fibrillation in non-insulin-dependent diabetics with acute myocardial infarction. Coron Artery Dis, 1994, 5: 767-771
1 Gibble FM, Ashcroft FM. Differential sensitivity of beta-cell and extrapancreatic K-ATP channels to gliclazide. Diabetologia, 1992, 42: 845-848
2 Lawrence CL, ProKs P, Rodrigo GC, et al Gliclazide produces high- affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells [J]. Diabetologia, 2001, 44 8: 1019-1025
3 Sakura H, Ammala C, Smith PA, et al Cloning and functional expression of the cDNA encoding a novel ATP - sensitive potassium channel subunit expressed in pancreatic beta-cells, brain, heart, and skeletal muscle[J]. FEBS Lett, 1995, 77 3: 338
4 Babenko AP, Aguilar Bryan L and Bryan J. A View of SUR/Kir6.X K-ATP channels [J ] . Annu Rev Physiol, 1998, 60: 667
5 Wang L, Cherednichenko G, Hernandez L, et al Preconditioning limits mitochondrial Ca2+ during ischemia in rat hearts: role of K-ATP channels. Am J Physiol Heart Circ Physiol, 2001, 280: H2321
6赵静,张凯伦,胡志伟等,二氮嗪预处理对大鼠心肌缺血-再灌注损伤的保护作用,中国胸心血管外科临床杂志[J],2005,12 04: 270-273.
7 Tilley Pain, Xi-Ming Yang, et al Opening of Mitochondrial K-ATP Channels Triggers the Preconditioned State by Generating Free Radicals. Circulation Research, 2000, 87: 460-466
8 Sasaki N, Sato T, Ohler A, et al Activation of mitochondrial ATP-dependent potassium channels by nitricoxide. Circulation, 2000, 101: 439–445
9 Yellon DM, Downey JM. Preconditioning the myocardium:from cellular physiology to clinical cardiology[J]. Physiol Rev, 2003, 83:1113-1151
10李寒等,二氮嗪对大鼠心肌缺血再灌注损伤的影响,中国体外循环杂志,2006,4 1:64
11 Billmen GE, Avendano GE, Hallliwill JR, et al The effects of theATP-dependent potassium channel antagonist, glyburide, on coronary blood flow and susceptibility to ventricular fibrillation in unanesthetized dogs. J Cardiovasc Pharmacol, 1993, 21: 197-204
12 TosaKi A, Szerdahelyi P, Engelman RM, et al J Pharmacol Exp Ther, 1995, 267: 1355-1362
13 Kosmas EN, Levy RD, Hussian SNA. Acute effects of glyburide on the regulation of peripheral blood flow in normal humans. Eur J Pharmacol, 1995, 274: 193-199
14 Wascher T C, Boes U. Forearm vascular reactivity is differentially influenced by gliclazide and glibenclamide in chronically treated type 2 diabetic patients [J]. Clin Physiol Funct Imaging , 2005, 25: 40-46
15 Reffelmann T, et al Post-stenotic coronary blood flow at rest is not altered by therapeutic doses of the oral antidiabetic drug glibenclamide in patients with coronary artery disease. Heart, 2002, 87 1: 57-60
16 ImamuraY, TomoikeH, Narishiget, et al Glibenclamide decreases basal coronary blood flow in anesthetized dogs, Am J Physiol, 1992, 263: 399-404
17 Roldano Scognamiglio, et al Effects of Treatment With Sulfonylurea Drugs or Insulin on Ischemia-Induced Myocardial Dysfunction in Type 2 Diabetes. Diabetes, 2002, 51 3: 808-812
18 McNulty PH, Pfau S, Deckelbaum LI, Effect of plasma insulin level on myocardial blood flow and its mechanism of action. Am J Cardiol, 2000, 85: 161–165
19 Enst T, Richwine RT, Bray MS, et al Insulin improves functional and metabolic recovery of reperfused working rat heart. Ann Thorac Surg, 1999, 67: 1682-1688
20 Abbink EJ, Pickkers P, Van Posendaol AJ, et al Vascular K-ATP channel blockade by glybenclamide, but not by acarbose, in patients with type 2 diabetes [J]. Clin Sci (Lond), 2002, 102 3: 307-314
21 Ohnson SP, Monster TBM, Olsen ML, et al Risk and short-term prognosis of myocardial infarction among users of antidiabetic drugs. AmericanJournal of Therapeutics, 2006, 13: 134-140
22 Fisman EZ, Tenenbaum A, Motro M, et al Oral antiabetic therapy in patients with heart disease. Herz, 2004, 29: 290-298
23 Schothorgh CE, Wilde AA. Sulfonylurea derivatives in cardiovascular research and in cardiovascular patients [J]. Cardiovasc Res, 1997, 34 1: 73-80
24 Halkin A, Roth A, Jonas M, et al Sulfonylureas are not associated with increased mortality in diabetics treated with thrombolysis for acute myocardial infraction [J]. J Thromb Thrombolysis, 2001, 12 2: 177-184
25 Hassouna A, Loubani M, Matata B M, et al Mitochondrial dysfunction as t he cause of t he failure to precondition the diabetic human myocardium [J]. CardiovascRes, 2006, 2: 450-458
26 Chan JC, Tomlinson B, Critchley JA et al Metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients. DiabetesCare, 1993, 16: 1035-1038