葡萄糖-胰岛素-钾极化液对犬重度心肌缺血/再灌注后心律失常和心电图的影响

目的探讨葡萄糖-胰岛素-钾合剂（GIK）对犬重度心肌缺血/再灌注（MI/R）后心律失常和心电图的影响。方法制备犬重度MI/R模型。再灌注前5min静脉分别输注生理盐水、GIK或GK（葡萄糖-钾液）。观察动物心电、血糖等的变化。结果犬重度MI/R引起心律失常,包括室性早搏、室速和室颤。再灌注期间静脉输注生理盐水、GIK或GK,未观察到室性心律失常发生率和严重程度有显著差异。但GIK可缩短再灌注期间心电图QRS波群时间。其中,再灌注4hQRS波群时间显著缩短,由对照组0.077±0.006s缩短至GIK组0.058±0.003s（n=6,P<0.01）。GK组与对照组比较无显著差异（n=6,P>0.05）。结论GIK对犬重度MI/R引起的室性心律失常无显著改善作用,但可缩短缺血/再灌注心脏的QRS波群时间,提示胰岛素可能影响MI/R心室除极。     

葡萄糖-胰岛素钾液对心肌缺血/再灌注犬血液流变学和血糖的影响

目的:观察近年推荐使用的大剂量葡萄糖胰岛素钾液（GIK）对急性心肌缺血/再灌注（MI/R）犬血液流变学特性的影响。方法:定量狭窄冠状动脉左前降支（血流量降低80%）制作犬心肌缺血/再灌注模型。将24只杂种犬随机分为GIK组、葡萄糖钾液（GK）组及生理盐水对照组（n=8）。再灌注同时分别静脉输注GIK、GK、生理盐水（2ml·h-1·kg-1）。在狭窄冠脉前和再灌注即刻及再灌注后1h、2h、4h抽取冠状静脉窦血,测定血液流变学和血糖变化。结果:缺血50min时各组犬血细胞比容、全血高切粘度、全血低切粘度较缺血前均有不同程度增高（P<0.05）。GIK组再灌注后各时间点血糖和血液流变学指标与缺血前及生理盐水对照组相比均无显著差异。GK组再灌注后2h和4h时血细胞比容（HCT）较生理盐水对照组增高（P<0.05）。再灌注后GIK组与生理盐水组血糖无明显升高,GK组再灌注后2h和4h血糖较对照组分别增加76%和92%（P<0.01）。结论:急性心肌缺血可致血液流变学特性显著改变,主要表现为HCT、ηbh、ηbl增高。本研究所用GIK的剂量不会导致血糖明显变化,且对MI/R过程中犬血液流变学无明显影响;本研究结果还提示,单独输注高糖可能对急性心肌缺血患者不利。     

极化液对缺血/再灌大鼠心肌细胞死亡及心脏功能的影响:胰岛素的关键作用

目的　探讨葡萄糖 胰岛素 钾极化液 (GIK)对心肌缺血 /再灌 (MI/R)后心肌细胞死亡(坏死和凋亡 )及心脏功能的影响 ,并比较和分析GIK各组分在其中的作用。方法　制备大鼠MI/R模型 ,分别用生理盐水、GIK、葡萄糖 钾液 (GK)或胰岛素干预分组。观察动脉血压、血糖、左室压等的变化 ,再灌注结束后检测心肌梗死或提取DNA检测心肌细胞凋亡。结果　MI/R造成明显的心脏功能障碍、心肌梗死和缺血区细胞凋亡。GIK与胰岛素 (而非GK)具有相似的减轻再灌注心肌损伤作用 ,包括减少心肌梗死范围 [(41 3± 8 3) %和 (39 6± 8 6) %比对照组 (54 4± 1 0 4) % ,q =4 34和q=4 90 ,P值均 <0 0 5]、减弱DNA梯带形成及促进再灌后心脏收缩 /舒张功能恢复。结论　GIK可减少心肌梗死、促进缺血心脏功能恢复 ,胰岛素可能通过抑制缺血心肌细胞凋亡在GIK心肌保护中发挥关键作用。     

高、低剂量极化液对缺血/再灌注心肌细胞凋亡及相关基因的影响

目的 :探讨高、低两种剂量葡萄糖 -胰岛素 -钾极化液 （GIK）对缺血 /再灌注 （MI/R）心肌超微结构 ,细胞凋亡及其相关基因的影响。方法 :制备兔MI/R模型 ,分别用生理盐水 ,低剂量极化液 （LGIK） ,高剂量极化液 （HGIK）干预分组。检验心肌组织SOD活性 ,原位末端标记 （TUNEL）法测定凋亡心肌细胞 ,免疫组化SP法测定Bcl 2 ,Fas的含量 ,在电镜下观察心肌细胞的超微结构。结果 :与对照组比较 ,HGIK组SOD活性增加 （P <0 .0 1） ,凋亡指数 （AI）和Fas含量减少 （P <0 .0 1） ,Bcl 2含量增加 （P <0 .0 1）。心肌细胞超微结构表现为损伤减轻。LGIK亦可增加SOD活性和Bcl 2含量 （P <0 .0 5 ） ,减少AI和Fas（P <0 .0 5 ）含量。结论 :GIK具有抗缺血 /再灌注损伤的作用 ,其机制可能是通过调节Bcl 2和Fas介导的心肌缺血 /再灌注细胞凋亡而实现。高剂量GIK对缺血 /再灌注心肌细胞的保护作用显著大于低剂量GIK（P <0 .0 5 ）。     

葡萄糖-胰岛素-钾液对缺血/再灌注心肌的保护作用

目的:观察极化液（葡萄糖-胰岛素-钾液,G IK）对急性心肌缺血/再灌注（M I/R）犬心脏功能、冠脉血流量及心肌损伤的影响,分析胰岛素在G IK上述效应中的作用。方法:制备犬M I/R模型,心肌定量缺血（左前降支血流量降低80%）50 m in,再灌注4 h。24只杂种犬随机分为G IK、葡萄糖-钾液（GK）和盐水对照组（n=8/组）,再灌注前5m in输注G IK、GK、生理盐水。观察冠脉血流量及血流动力学指标;检测不同时间血清乳酸脱氢酶（LDH）、肌酸激酶（CK）活性;再灌注4 h后测量并计算心肌梗死范围。结果:与盐水对照组相比,G IK明显增加左前降支冠脉血流量（CBFLAD）,改善再灌注后左室收缩及舒张功能,降低血清CK、LDH,减少心肌梗死范围,而GK无上述作用。结论:再灌注时输注G IK可促进再灌注心脏功能恢复及减轻心肌损伤,该作用可能与G IK增加冠脉血流量有关;胰岛素是G IK上述作用的关键成分。     

胰岛素对缺血/再灌注心肌的保护作用

目的 :探讨胰岛素在心肌缺血 /再灌注 （I/ R）期间对心肌细胞的保护作用。方法 :制备兔 I/ R模型并将其随机分为 3组 ,分别于缺血前 30 min予以葡萄糖 -胰岛素 -钾 （GIK） （葡萄糖 15 0 g/ L ,胰岛素 10 0 U/ L ,钾 80 m mol/ L ）、胰岛素 （10 0 U / L ）、生理盐水静脉注射 （1.2 m l/ h） ,然后实施 40 min的心肌局部缺血和 3h的再灌注。采集并处理心肌血流动力学指标 ,检验乳酸脱氢酶 （L DH ）、肌酸激酶 （CK）活性。 3h后 ,采用 E- vans蓝 - TTC法测量心肌梗死范围。结果 :与对照组比较 ,GIK及胰岛素组在血流动力学 （L VEDP,± dp/ dtmax） ,CK,L DH、梗死范围测量等均表现为损伤减轻 ,且这两组间未见明显差异。结论 :在 I/ R的过程中 ,GIK合剂除了提供能量外 ,其中的胰岛素也发挥了重要的心肌保护作用     

胰岛素对心肌缺血/再灌注损伤兔心肌组织中髓过氧化物酶活性的影响及意义

目的观察胰岛素是否能够通过减轻中性粒细胞(PMN)在心肌组织中的浸润、聚集而抑制炎症反应,从而减轻心肌缺血/再灌注(MI/R)损伤。方法建立兔MI/R模型,分为假手术组、GIK组、GK组和对照组,后三组缺血45 min/再灌注6 h,检测各组血浆肌酸激酶同工酶(CK-MB)活性、高敏C反应蛋白(hs-CRP)水平,以及心肌组织中髓过氧化物酶(MPO)活性,利用Evans blue-TTC染色法测定心脏梗死面积。结果与对照组相比,GIK组CK-MB活性下降(P<0.01)、心肌梗死面积减小(P<0.01)、MPO活性降低(P<0.01)、hs-CRP水平下降(P<0.01),GK组上述各指标则无明显变化(P均>0.05)。结论胰岛素能够减轻兔MI/R过程中PMN在心脏组织中的聚集,这可能是胰岛素保护MI/R心脏的重要机制之一。     

极化液给予时机对缺血/再灌注犬心脏功能及心肌损伤的影响

目的:探讨不同时间开始给予极化液（葡萄糖-胰岛素-钾液,G IK）对犬心肌缺血/再灌注（M I/R）后心脏功能及心肌细胞损伤的影响。方法:制备犬M I/R模型,心肌定量缺血（左前降支血流量降低80%）50 m in,再灌注4 h。分别于:①再灌注前30 m in（再灌注前）、②再灌注即刻（再灌注时）、③再灌注后1 h（再灌注后）给予G IK。观察对动脉血压、心率、左室压的影响及测定心大静脉血清乳酸脱氢酶（LDH）、肌酸激酶（CK）活性,再灌注结束后检测心肌梗死率或细胞凋亡指数。结果:与再灌注后组相比,再灌注前组和再灌注时组可明显改善再灌注后左室收缩及舒张功能,降低血清CK、LDH活性,减少心肌梗死范围[分别为（5.9±1.1）%和（5.2±0.8）%vs（9.1±1.2）%,均P<0.01]、抑制心肌细胞凋亡的发生[（4.6±0.9）%和（3.7±1.1）%vs（8.9±2.3）%,均P<0.05]。结论:再灌注早期给予G IK可降低M I/R引起的心肌细胞损伤,促进再灌注后心脏功能的恢复,在再灌注后1 h给予G IK对心脏的上述保护作用则明显减弱。     

作者单位：030001山西省太原市 山西医科大学基础医学院生理学系,细胞生理学山西省重点实验室通讯作者：贺忠梅,E-mail：hezmei@126.com

目的 探讨低氧诱导因子-1α(HIF-1α)稳定表达对大鼠心肌缺血再灌注细胞凋亡的影响及可能机制。方法 采用结扎冠脉左前降支45min,再灌注3h的方法,构建大鼠心肌缺血再灌注损伤模型;实验分为假手术组(Sham)、心肌缺血/再灌注组(MI/R)、HIF-1α活化剂DMOG 心肌缺血/再灌注组(D MI/R)、HIF-1α抑制剂YC-1 心肌缺血/再灌注组(YC-1 MI/R);采用全自动生化分析仪测定血清心肌酶(CK-MB,LDH)活性;Western blot检测心脏组织HIF-1α蛋白表达;Evens blue/TTC染色测定心肌梗死面积;TUNEL染色及Caspase-3,8,9活性测定心肌细胞凋亡。结果 (1)与MI/R 组相比,D MI/R 组的HIF-1α蛋白表达量明显增加,心肌酶CK-MB、LDH的活性降低,心肌梗死面积明显减小,并且心肌组织的病理损伤减轻;(2)稳定HIF-1α表达可明显降低心肌细胞凋亡率,且部分逆转了缺血再灌注后心肌组织Caspase-9与Caspase-3的活性升高。结论 HIF-1α稳定表达可抑制线粒体途径介导的心肌细胞凋亡,从而发挥对缺血再灌注损伤的心脏保护效应。     

抗TNF-α中和抗体通过升高脂联素水平减轻小鼠心肌缺血/再灌注损伤的作用

目的:阐明心肌缺血/再灌注(MI/R)时,脂联素(APN)与肿瘤坏死因子-α(TNF-α)的关系,以及使用中和抗体阻断TNF-α可否提高血浆APN,进而发挥心肌保护作用。方法: 96只成年雄性C57小鼠和36只ob/ob小鼠均采用30 min缺血/再灌注(I/R)建立MI/R模型。96只C57小鼠分为假手术组、手术+盐水对照组及手术+抗TNF-α中和抗体治疗组(n=32);36只ob/ob小鼠分为ob/ob假手术组、ob/ob手术+盐水对照组及ob/ob手术+抗TNF-α中和抗体治疗组(n=12)。假手术或缺血20 min后,腹腔注射给予单次抗TNF-α中和抗体或盐水干预。分别采用ELISA检测TNF-α与APN血浆水平;小鼠心脏超声评估心脏LVEF;伊文氏蓝/TTC染色检测心脏梗死面积;以及TUNEL/Caspase-3活性检测观察心肌细胞凋亡。结果: 血浆ELISA测定发现,MI/R后,小鼠血浆TNF-α水平在再灌后1 h即显著升高,后缓慢下降。注射抗TNF-α中和抗体可在再灌后1 h即中和TNF-α（P<0.01）,同时在再灌注3 h、8 h、1 d及3 d后4个时间点,较给予盐水对照显著升高血浆APN（P<0.01）。通过小鼠心脏超声、伊文氏蓝/TTC染色和TUNEL/Caspase-3活性检测发现,与给予盐水的对照相比,腹腔注射抗TNF-α中和抗体可提高小鼠的心肌功能（P<0.05）、减少梗死面积（P<0.01）及心肌细胞的凋亡（P<0.01）。而在ob/ob小鼠中,通过以同样的实验方法证实,单次注射抗TNF-α中和抗体已不能提高血浆APN的含量,其减轻心肌损伤的作用同样被显著削弱,但给予APN球状片段仍可发挥心肌保护作用。结论: 以抗TNF-α的中和抗体阻断TNF-α可逆转MI/R后血浆APN的降低并发挥心肌保护作用,提示抗TNF-α中和抗体发挥的心肌保护作用可能部分通过提高APN实现。     

Comparison of low-dose dobutamine stress echocardiography and echocardiography during glucose-insulin-potassium infusion for detection of myocardial viability after anterior myocardial infarction

BACKGROUND: Low-dose dobutamine stress echocardiography (LDDSE) is one of the methods most used to assess myocardial viability. Glucose-insulin-potassium (GIK) infusion has been shown to increase contraction of the ischemic zone. The aim of this study was to compare LDDSE and echocardiography during GIK infusion for detection of myocardial viability. METHODS: Thirty-two patients who had first anterior myocardial infarction (MI) without previous MI were included in the study. Echocardiographic evaluation was carried out on the 7th +/- 2 days after MI. During continuous electrocardiographic, blood pressure and echocardiographic monitoring, an intravenous infusion of dobutamine (3 microg/kg body weight/min) was started with an infusion pump, continued for 5 min and then increased to 5 microg/kg/min and 10 microg/kg/min for another 5 min. The GIK protocol consisted of a fixed dose of insulin (100 microU/kg/h intravenously) and a variable glucose/potassium infusion rate. GIK echocardiography was done at baseline and after 60 min of GIK. The detected viable myocardium was defined as one or two scores decreasing in at least two adjacent abnormal segments during LDDSE and GIK echocardiography. RESULTS: Under resting conditions 225 segments (44%) were normokinetic, 21 segments (4%) dyskinetic, 117 segments (23%) akinetic and 149 segments (29%) hypokinetic. Viability was detected in 20% (57 segments) of the asynergic segments at baseline with GIK echocardiography and in 22% (62 segments) of those segments with LDDSE (P < 0.05). Left ventricular wall motion score index at baseline was 1.87 and it decreased significantly indicating improvement in left ventricular systolic function during both LDDSE and GIK echocardiography (P < 0.001, versus 1.75 and 1.76 respectively). The agreement between LDDSE and GIK echocardiography for detection of myocardial viability was 96%. CONCLUSION: We have shown that GIK echocardiography is similar to LDDSE for detection of myocardial viability. With the support of further clinical studies GIK echocardiography could be used to detect myocardial viability after acute MI.     

The beneficial effect of insulin, glucose, and dipyridamole on regional left ventricular function early after acute myocardial infarction

BACKGROUND: High-dose glucose-insulin-potassium (GIK) solution has beneficial effects on reducing mortality in acute myocardial infarction. Dipyridamole (DIP) is a powerful antioxidant and increases adenosine concentration. Experimentally, GIK and DIP have additive protective effects in ischemia-reperfusion injury. AIM: This work aims to assess the acute effects of DIP alone, GIK alone, and GIK+DIP on left ventricular function in patients evaluated early after an acute myocardial infarction. METHODS: Ten male patients (age 63+/-11 years) with uncomplicated acute myocardial infarction were evaluated within 3 days after admission. All had been treated with systemic thrombolysis and were on full therapy (including beta-blockers) at the time of testing. They underwent stress echocardiography [2D echo, with wall motion score index (WMSI) evaluated in a 16-segment model of the left ventricle, with each segment scored from 1=normal to 4=dyskinetic] during low-dose DIP alone (0.28 mg/kg in 4 min); GIK alone (4-h infusion of glucose 30%, 25 insulin units, and 40 mEq of KCl, at an infusion rate of 1.5 ml/kg/h); and GIK+DIP. RESULTS: Regional systolic function (baseline WMSI=1.69+/-0.2) improved after DIP (1.54+/-0.1), GIK (1.54+/-0.1), and, to a greater extent, after GIK+DIP (1.33+/-0.2; p<0.001 vs. baseline; p<0.05 vs. DIP; p<0.05 vs. GIK). CONCLUSION: High-dose GIK has an acute beneficial effect on regional left ventricular function in patients with acute myocardial infarction. This beneficial effect is potentiated by low-dose DIP coadministration.     

Identification of viable myocardium in patients with chronic coronary artery disease and myocardial dysfunction: comparison of low-dose dobutamine stress echocardiography and echocardiography during glucose-insulin-potassium infusion

Low-dose dobutamine stress echocardiography (LDDSE) is one of the methods most used to assess myocardial viability. Glucose-insulin-potassium (GIK) has been shown to increase contraction of the ischemic zone. The aim of this study was to compare LDDSE and echocardiography during GIK infusion for detection of myocardial viability in patients with chronic coronary artery disease (CAD) and myocardial dysfunction. Twenty-one patients who had chronic CAD and myocardial dysfunction were included in the study. Glucose-insulin-potassium protocol consisted of a fixed dose of insulin (100 microU/kg/hour IV) and a variable glucose/potassium infusion rate. GIK echocardiography was made at baseline and after 60 minutes of GIK infusion. During continuous electrocardiographic, blood pressure, and echocardiographic monitoring, an intravenous infusion of dobutamine (3 microg/kg body weight/min) was started with an infusion pump and continued for 5 minutes and then increased to 5 microg/kg/min and 10 microg/kg/min for another 5 minutes. The detected viable myocardium was defined as 1 or 2 scores decreasing in at least 2 adjacent abnormal segments during LDDSE and GIK echocardiography. Viability was detected in 19% (52 segments) of the asynergic segments at baseline with GIK echocardiography and 16% (44 segments) of those segments with LDDSE (p>0.05). Left ventricular wall motion score index at baseline was 2.24+/-0.35 and it decreased significantly during both LDDSE (p=0.004 vs 2.11+/-0.36) and GIK echocardiography (p=0.001 vs 2.09+/-0.32). The agreement between LDDSE and GIK echocardiography for detection of myocardial viability was 95%. This study shows that GIK echocardiography is similar to LDDSE for detection of myocardial viability. With the support of further clinical studies GIK echocardiography can be used to detect myocardial viability in patients with chronic CAD.     

Effects of glucose-insulin-potassium solution added to reperfusion treatment in acute myocardial infarction.

OBJECTIVE: Reperfusion treatment modalities used in the routine treatment protocols of acute myocardial infarction (AMI) were found to be ineffective in establishing the nutritional cellular reperfusion in the microvascular environment even they succeed to open the infarct related artery. Glucose-insulin-potassium (GIK) solution, which is presumed to stimulate the glycolytic pathway, is experimentally proven to be the most efficacious substrate for the preservation of energy production and therefore the myocardial viability, in the setting of acute ischemia. METHODS: We compared, 54 patients who suffered AMI and received GIK solution (300 g glucose+50 IU crystallized insulin+80 mEq potassium chloride in one liter solution) in addition to conventional treatment (GIK group) with 27 patients who were traditionally treated (control group) for in-hospital and early-term (1 month) cardiac morbidity. We also compared the two groups in terms of heart rate variability (HRV). RESULTS: Eight patients in the control group developed new-onset symptomatic congestive heart failure whereas only 5 patients in GIK group were found to have such a cardiac morbidity (p=0.01). Reduced HRV (<50 ms) was found in 3 patients of control group whereas no patient in GIK group had abnormal HRV (p=0.01). CONCLUSION: The GIK solution decreased the incidence of new-onset symptomatic congestive heart failure and low HRV after myocardial infarction. Larger multicenter trials need to resolve the questions on the efficiency of metabolic intervention with GIK solution in acute myocardial infarction.     

Effect of glucose-insulin-potassium infusion on myocardial damage due to percutaneous coronary revascularization

Percutaneous coronary intervention has been known to cause myocardial damage as a result of microvascular dysfunction due to microembolization and microinfarction. Previous studies have shown that glucose-insulin-potassium (GIK) infusion decreases mortality in patients with acute myocardial infarction. Therefore, in this study, we aimed to investigate the effect of GIK infusion on myocardial damage due to percutaneous coronary revascularization. A total of 52 consecutive nondiabetic patients diagnosed with non-ST-elevation acute coronary syndrome and designated for elective percutaneous coronary intervention were randomized in a double-blind fashion into GIK and normal saline groups. GIK infusion (30% dextrose, 300 U insulin, and 60 mEq potassium chloride) at a dose of 1.5 ml/kg/hour was initiated 24 hours before the intervention and continuing during and until 1 hour after the intervention. Troponin I levels were recorded in venous blood samples before and 12 and 24 hours after the intervention. The increase in troponin I was significantly lower at 12 and 24 hours in the GIK group compared with those of the saline controls (p=0.022 and p=0.005, respectively). GIK infusion initiated 24 hours before coronary stenting for non-ST-elevation acute coronary syndrome resulted in less myocardial damage as determined by postprocedure troponin I levels.     

Effects of glucose-insulin-potassium (GIK) on myocardial blood flow and metabolism in canine endotoxin shock

Glucose-insulin-potassium (GIK) has beneficial effects during endotoxin shock, possibly through improvement of myocardial function, but the mechanism is not clear. We have studied the effects of GIK on left ventricular function, coronary flow, and oxygen consumption in controls and dogs treated with endotoxin (1.5 mg/kg-1). The animals were anaesthetized (etomidate 4 mg/kg-1/hr-1) and ventilated (N2O:O2 = 2:1). We have measured left ventricular pressure, left ventricular end-diastolic pressure (LVEDP) and LVdP/dt, systemic blood pressure, cardiac output (CO; thermodilution), coronary blood flow (CBF; radioactive microspheres), and oxygen content and lactate in arterial and coronary sinus blood. Endotoxin caused a rapid fall of CO and blood pressure with a temporary recovery followed by gradual circulatory collapse. GIK infusion (50% glucose, 2 g/kg-1 bw, 8 mmol KCl, and 3 U insulin/kg-1 bw) increased CO (56%), CBF (61%), blood pressure (21%), LVEDP (77%), and LVdP/dt (28%), and systemic vascular resistance decreased (23%). Stroke work (80%) and tension time index (42%) decreased during shock, but GIK temporarily improved these variables. The ratio of stroke work, respectively tension time index to oxygen consumption, suggests that myocardial efficiency decreased during shock and improved after GIK. Endotoxin decreased the ratio of endo- to epicardial flow. GIK did not change this ratio. However, for the same endo to epi ratio, increased CBF implies increased flow to endocardium.     

Patient Self-Management of Oral Anticoagulant Therapy: An International Update

While glucose-insulin-potassium (GIK) has been suggested to be cardioprotective, few studies have assessed its effect on anatomic myocardial infarct size in an ischemia-reperfusion protocol. Anesthetized rabbits were subjected to a 30-minute coronary artery occlusion followed by 4 hours of reperfusion. Rabbits were pretreated with a GIK infusion lasting 90 minutes or placebo. GIK infusion markedly increased serum glucose levels by over twofold, but the area of necrosis expressed as the area at risk was not reduced by GIK infusion (25%) versus control (20%). In a rabbit infarct model of ischemia/reperfusion, GIK failed to reduce myocardial infarct size.     

Effects of glucose-insulin-potassium infusion on myocardial perfusion and left ventricular remodeling in patients treated with primary angioplasty for ST-elevation acute myocardial infarction

The role of glucose-insulin-potassium (GIK) infusion in the management of acute coronary syndrome is controversial. Limited data are available on the effects of adjunctive high-dose GIK (30% glucose, 50 IU of insulin, 80 mEq of potassium chloride infused at 1.5 ml/kg/hour over 24 hours) on myocardial perfusion and left ventricular (LV) remodeling in patients treated with primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction. In this prospective study, 73 patients were randomized to receive GIK infusion (n = 40) or saline (placebo, n = 33) in addition to standard therapy. The primary end points were myocardial perfusion after PCI and LV remodeling at 6 months. Thrombolysis In Myocardial Infarction frame count and myocardial blush grade were evaluated before and after reperfusion treatment. LV end-diastolic and end-systolic volumes, ejection fraction, and wall motion score index were assessed in each patient after PCI and after 6 months. Although no differences in final Thrombolysis In Myocardial Infarction flow were observed between the 2 groups, myocardial blush grade 3 was more frequently achieved in the GIK group (p <0.05). At 6 months, ventricular remodeling was more often observed in the control group (24% vs 3%, p <0.05). In conclusion, GIK infusion in adjunct to primary PCI in patients with ST-segment elevation myocardial infarction was safe, improved myocardial perfusion after revascularization, and was associated with less LV remodeling at follow-up.     

Response of hypertrophic heart myocardial glycogen to GIK and hypovolemic shock

Glucose-insulin-potassium (GIK) given during myocardial ischemia or anoxemia results in improved myocardial function and augments energy reserves of myocardial glycogen (MG). Because many patients with heart disease also have myocardial hypertrophy, our purpose was to examine whether similar elevations in MG can occur in hypertrophic hearts with GIK administration and to study the effect of hypovolemic shock on those MG levels. Mongrel dogs (n = 5) with myocardial hypertrophy underwent serial myocardial biopsies of the left (LV) and right (RV) ventricles, and blood samples were followed by GIK infusion (14.5 ml/kg/hr) for 2 hr. after which the dogs were subjected to 2 hr of hypovolemic shock (mean arterial pressure = 40 mmHg). It was found that after GIK infusion MG was consistently elevated in both RV (.43 +/- .02 to .60 +/- .04 g%) and LV (.63 +/- .07 to .71 +/- .01 g%) and FFA declined (.20 +/- .05 to .05-.01 mEq/liter). The MG responded to hypovolemia by further significant elevations (RV 1.16 +/- .33; LV .82 +/- .17), as did FFA (.38 +/- .21). These results indicate that hypertrophic hearts can indeed respond to GIK infusion by increasing MG in both the RV and LV, as do normal hearts. These hearts then submitted to hypovolemic shock showed a further elevation of MG. The elevated insulin levels post-GIK resulted in suppression of FFA. Thus GIK administration may have a sparing effect on energy stores of the heart during hypovolemic shock, which could have clinical implications in the treatment of patients with hypertrophic myocardia.