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。     

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     

GIK对缺血/再灌注犬心肌超微结构的影响

目的:观察葡萄糖-胰岛素-钾液（GIK）、葡萄糖-钾液（GK）对急性心肌缺血/再灌注（MI/R）犬心肌缺血区内心肌细胞改变的影响,分析GIK中的胰岛素对MI/R心肌细胞的保护作用。 方法: 将犬心肌定量缺血(左前降支血流量降低80%) 50 min,再灌注4 h,建立犬MI/R模型。24只杂种犬随机分为GIK组、GK组和盐水对照组(n=8),于再灌注前5 min,分别输注GIK、GK和生理盐水。再灌注4 h后,计算梗死区占缺血区重量的百分比,并制作电镜切片于透射电镜下观察。 结果: GIK可显著减少心肌梗死(MI)的范围［GIK组（5.2±0.8）% vs. 盐水对照组（9.4±0.8）%,P<0.05］;而GK组MI的范围（8.5±0.9）%则与盐水对照组无明显差异。与盐水对照组相比,GIK组对非缺血心肌的超微结构无影响,对缺血心肌有一定的保护作用。GK对缺血心肌无保护作用。结论: 再灌注时,静脉输注GIK可减轻心肌超微结构的损伤,其中的胰岛素是GIK上述作用的关键成分。     

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。     

雷诺嗪对豚鼠在体心肌缺血-再灌注损伤心律失常的预防作用

目的:探讨雷诺嗪对豚鼠在体心肌缺血-再灌注损伤(MIRI)模型的心律失常的影响及其可能作用机制.方法:将40只MIRI模型豚鼠分为4组:假手术组,对照组(MIRI组),雷诺嗪注射组和雷诺嗪持续灌注组,观察各组超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、再灌注心律失常发生情况.结果:与MIRI组比较,雷诺嗪注射组、雷诺嗪持续灌注组SOD活性增高,MDA含量降低,发生心室颤动的只数减少.结论:雷诺嗪可增强SOD活性,降低MAD水平,对抗MIRI过程的作用,减少再灌注心律失常的发生.     

肾素-血管紧张素对大鼠心肌缺血和缺血再灌注心律失常影响的实验研究

本研究观察肾素 -血管紧张素系统 (RAS)对大鼠心肌缺血和缺血再灌注后心律失常的影响 ,以及给予氯沙坦 (AT1受体拮抗剂 )和培多普利 (ACE抑制剂 )干预的结果。1 方法 :结扎大鼠左冠状动脉前降支 (LAD)造成心肌梗死 ,30min后松解结扎线再灌注心肌 6 0min ;假手术组只穿线不结扎。大鼠随机分为四组 :即假手术组 (S组 )、生理盐水组 (C组 )、氯沙坦组 (L组 ,5mg/kg体重 )、培多普利组 (P组 ,3mg/kg体重 )。每组大鼠 19只 ,其中每组有 8只结扎LAD30min后 ,于心肌再灌注 5min时 ,从心脏取血 ,测量血浆去甲肾上腺素 (NE)水平 ;各组其余 11…     

腺苷对大鼠心肌缺血再灌注心律失常的影响

目的 :研究腺苷对大鼠心肌缺血再灌注 （I/ R）致心律失常的影响以及与 ATP敏感性钾通道 （KATP）的关系。方法 :采用结扎大鼠左冠状动脉前降支造成缺血 10 min,然后再灌注 15 m in,诱发室性心律失常。在心肌缺血前分别给予腺苷 （2 ,6 mg/ kg）及 KATP阻断剂格列本脲 （Glib,7.5 mg/ kg）。结果 :1与对照组相比 ,腺苷 2 ,6 m g/ kg两剂量组可明显减少 I/ R室颤的发生率 （P<0 .0 1） ,降低心律失常评分分值 （P<0 .0 1） ,能明显降低磷酸肌酸激酶 （CPK ）和乳酸脱氢酶 （L DH）活性 （P<0 .0 1）。 2 Glib阻断 KATP后 ,诱发出严重的室性心律失常 ,且 CPK,L DH值均显著高于对照组 （P<0 .0 1）。 3腺苷 6 mg/ kg在 Glib阻断 KATP后 ,亦可降低室性心律失常分值 ,降低 CPK,L DH水平 ,同Glib组相比较 ,P<0 .0 1或 P<0 .0 5。结论 :腺苷对大鼠 I/ R心肌损伤有明显的保护作用 ,而 KATP的开放可能是其保护作用的部分机制     

缬沙坦抗大鼠心肌缺血再灌注心律失常的作用

缺血再灌注 (ischemia reperfusion ,I/R)心律失常是心肌I/R损伤中一种最常见的表现 ,特别是快速恢复冠状动脉血流可诱发致命性心律失常室性心动过速 (室速 )和心室颤动(室颤 )。动物实验已证实 ,血管紧张素转换酶抑制剂(ACEI)具有抗I/R心律失常作用。但血管紧张素Ⅱ受体(AT1受体 )拮抗剂缬沙坦在心肌I/R心律失常中的作用尚未见报道。本研究利用大鼠心肌I/R模型 ,观察缬沙坦对大鼠心肌I/R心律失常的作用。1.材料与方法 :4 8只雄性Sprague dawley大鼠 ,体重(2 98± 2 2 )g ,随机均分三组 ,灌喂给药。缬沙坦组 30mg·kg-1·d-1,苯那普…     

缝隙连接蛋白43与心肌缺血再灌注心律失常的研究进展

近年来,心肌缺血再灌注损伤(myocardial ischemic-reperfusion injury,MIRI)的治疗和预防是心血管领域新兴的研究课题之一。缝隙连接(gap junction,GJ)是心脏电生理的基本结构。缝隙连接蛋白(connexin,Cx)是缝隙连接的基本单位。缝隙连接蛋白43(connexin 43,Cx43)是心脏Cx家族中最丰富的成员,Cx43的正常表达对于心脏发育、电耦联的心肌细胞活性和心肌功能的协调至关重要。Cx43与MIRI之间的关系已成为当前研究的重点。该文就Cx43与心肌缺血再灌注心律失常的关系作一综述。     

气体信号分子硫化氢对大鼠心肌缺血再灌注心律失常的影响

目的:研究硫化氢(H2S)对大鼠心肌缺血再灌注室性心律失常的影响及作用机制。方法:以硫化氢钠(NaHS)作为H2S供体,建立心肌缺血再灌注损伤动物模型,将实验大鼠按随机原则分为假手术组、心肌缺血再灌注(I/R)组、H2S+I/R组及H2S+KATP通道阻断剂(格列本脲)+I/R组,监测大鼠心率(HR)、动脉压(ABP)、左心室内压(LVP)及左室内压力最大上升速率(+dp/dtmax)、左室内压力最大下降速率(-dp/dtmax)等血流动力学指标,观察大鼠室性心律失常的发生情况。结果:I/R组ABP[(12.6±1.3)kPa∶(14.2±1.3)kPa]、LVP[(13.7±1.1)kPa∶(15.6±1.6)kPa]、+dp/dtmax[(398±52)kPa/s∶(516±63)kPa/s]、-dp/dtmax[(307±27)kPa/s∶(388±52)kPa/s]均较假手术组显著降低(P均0.05);H2S+I/R组HR[(309±11)次/min∶(395±12)次/min、(387±10)次/min]、ABP[(10.0±1.3)kPa∶(12.6±1.3)kPa、(11.7±1.2)kPa]、LVP[(11.0±1.2)kPa∶(13.7±1.1)kPa、(12.6±1.0)kPa]显著低于I/R组及H2S+格列本脲+I/R组(P均0.05),且各项指标均显著低于假手术组;H2S+格列本脲+I/R组各项指标与I/R组相似,无显著差别(P均0.05)。H2S+I/R组室性早搏数[(483±136)个∶(765±175)个、(700±167)个]、室性心动过速发生率(51%∶86.5%、86.3%)、室颤(33.5%∶66.5%、60.3%)死亡率(0:27%、23%)以及室性心律失常评分[(2.6±0.7)分∶(4.3±0.9)分、(4.1±0.7)分]明显低于I/R组及H2S+格列本脲+I/R组(P均0.05),I/R组及H2S+格列本脲+I/R组间无显著差异(P均0.05)。结论:硫化氢可减少大鼠心肌缺血再灌注室性心律失常的发生,其作用机制可能与开放细胞内KATP通道有关。     

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。     

Effect of magnesium on ischemic and reperfusion arrhythmias in a canine model with diminished collateral blood flow

Summary To assess the effects of elevated serum magnesium on ischemic and reperfusion arrhythmias, the left anterior descending coronary artery was cannulated and perfused by a shunt from a carotid artery in 20 open-chest anesthetized dogs. Ischemia was caused for 30 minutes by shunt occlusion and retrograde diversion of collateral blood flow. Dogs (10/group) were treated prior to occlusion with either saline or MgSO₄ (100 mg/kg IV). Plasma magnesium rose from 0.72±0.05 mM to 3.89±0.29 mM before occlusion (p<0.01) and fell to 3.28±0.21 mM just before reperfusion (p<0.01). Compared to saline, magnesium significantly slowed heart rate (113±4 beats/min vs. 124±3 beats/min, p<0.05), lowered arterial blood pressure (90±2 mmHg vs. 111±4 mmHg, p<0.05), and reduced myocardial blood flow to the ischemic zone before the occlusion (59±7 ml/min/100 g vs. 83±5 ml/min/100 g, p<0.01). The incidence of ventricular tachycardia during occlusion was 80% in the saline group and 70% in the magnesium group (p=1.0). The time required for a monophasic complex to develop in an electrogram over the ischemic zone was 4.5±0.24 minutes in the saline group and was not altered by magnesium (4.6±0.18 minutes). The incidence of reperfusion-induced ventricular fibrillation was 100% in both groups. The results suggest that acute infusion of magnesium offers little protection against ventricular tachyarrhythmias evoked by occlusion or reperfusion in a canine model of myocardial ischemia with diminished collateral blood flow.     

Ventricular fibrillation during partial reperfusion following severe myocardial ischemia in the canine model

The authors examined whether partial reperfusion protects against reperfusion ventricular fibrillation (VF) following severe acute myocardial ischemia. Fifty-seven dogs were divided into two groups. In group A (n = 21), the left anterior descending coronary artery was occluded for 10 minutes, followed by full reperfusion. In the remaining 36 dogs (group B), myocardial ischemia was induced by retrograde blood flow (RBF) for 10 minutes. Thereafter, these dogs were divided into three subgroups: in group B1 (n = 10), full reperfusion was made by a carotid-left anterior descending coronary artery bypass; in group B2 (n = 13), partial reperfusion was achieved by collateral flow into the ischemic zone due to stopping RBF; in group B3 (n = 13), RBF was continued for an additional 5 minutes. During 10 minute ischemia, the myocardial blood flow at the ischemic zone measured by the H2 gas-clearance method was 12.3 +/- 2.0 ml/min/100 g in A, 3.4 +/- 0.9 ml/min/100 g in B1, 4.7 +/- 0.6 ml/min/100 g in B2, and 4.7 +/- 0.6 ml/min/100 g in B3 (A vs B1, p less than 0.02; A vs B2 and B3, p less than 0.01). Maximal ST-segment elevation was 11.4 +/- 1.8 mV in A, 28.2 +/- 2.7 mV in B1, 25.1 +/- 3.0 mV in B2, and 27.0 +/- 1.9 mV in B3 (A vs B1, B2, and B3, p less than 0.001). Maximal conduction delay was 48.6 +/- 9.4 ms in A, 106.4 +/- 5.2 ms in B1, 101.6 +/- 9.9 ms in B2, and 91.2 +/- 5.1 ms in B3 (A vs B1, B2, and B3, p less than 0.001). The incidence of reperfusion VF was 14% (3/21) in A, 80% (8/10) in B1, and 69% (9/13) in B2 (A vs B1, p less than 0.001; A vs B2, p less than 0.005). In group B3, VF occurred in only 1 of 13 dogs for the additional 5 minutes. It is concluded that reperfusion VF occurred frequently when ischemia was severe even though the duration of ischemia was short (B1), and that reperfusion VF was not prevented by partial reperfusion when the ischemia was severe (B2).     

银杏黄酮对急性心肌缺血/再灌注的药理作用

目的本研究通过观察银杏黄酮对家兔心肌缺血/再灌注的作用,为其临床应用寻找新的证据。方法家兔随机分为2组,对照组和银杏黄酮组,每组5只,口服给药,连续7d。以常规方法制备兔心肌缺血/再灌注模型。记录心率、血压、左心室内压、左心室内压微分变化。同时观察银杏黄酮对家兔急性心肌缺血/再灌注治疗后减轻心肌梗死的情况。结果心肌缺血及再灌注后心率、血压、左心室内压等在银杏黄酮治疗组与正常对照组无显著差异。左心室内压微分在心肌缺血和缺血/再灌注中,银杏黄酮组与对照组有显著差异（P<0.05）。银杏黄酮治疗后对家兔急性心肌缺血/再灌注可减轻心肌梗死,银杏黄酮组与对照组有显著差异（P<0.01）。结论银杏黄酮对急性心肌缺血/再灌注后心率、血压、心左室内压无明显影响,但却非常明显地减少由于缺血所造成的心肌组织的梗死面积。     

低强度神经节丛刺激对正常心室电生理性质和急性心肌缺血室性心律失常发生的影响

目的 研究低强度神经节丛(GP)刺激对正常心室电生理性质和急性心肌缺血室性心律失常发生的影响.方法 体重18～25kg的正常成年杂种犬39只随机分为正常心脏组(n=12)和急性心肌缺血组(n=27,其中对照组12只,低强度GP刺激组15只),以2根多极电生理导管记录左、右心室局部电图,以自制Ag-AgC1电极记录左、右心室单相动作电位.在正常犬,分别在6h低强度GP刺激前和刺激后测量心室各部位有效不应期(ERP)、动作电位时限(APD),APD回复性质和APD交替以及血清乙酰胆碱和去甲肾上腺素浓度;在急性心肌缺血犬,比较室性心律失常的发生情况.结果 在正常犬,6h低强度GP刺激显著延长心室各部位ERP及APD(P＜0.05),但未改变其空间离散度;6h低强度GP刺激促进APD交替发生但不改变APD回复曲线斜率及其空间离散度;6h低强度GP刺激后血清去甲肾上腺素和乙酰胆碱水平均显著增加(P＜0.05).在急性心肌缺血犬,低强度GP刺激组室性心律失常的发生率显著低于对照组(P＜0.05).结论 低强度GP刺激不增加正常心脏室性心律失常的风险且有助于抑制急性心肌缺血心脏室性心律失常的发生.     

Protective effects of melatonin on myocardial ischemia/reperfusion injury in vivo

The production of oxygen free radicals has been strongly implicated as an important pathophysiological mechanism mediating myocardial ischemia/reperfusion (I/R) injury. Various antioxidants have cardioprotective effects. Melatonin, an indoleamine synthesized by the pineal gland, is a potent antioxidant and a direct free radical scavenger. This is the first in vivo study to evaluate the effect of melatonin (0.5, 1.0, and 5.0 mg/kg, i.v. bolus) on myocardial I/R injury in anesthetized Sprague-Dawley rats. Results demonstrate that pretreatment with intermediate or high doses of melatonin (1.0 and 5.0 mg/kg) at 10 min before left coronary artery occlusion markedly suppressed ventricular tachycardia (VT) and ventricular fibrillation (VF), while reducing the total number of premature ventricular contractions and total duration of VT and VF that occurred during the 45-min ischemic period. Pretreatment with melatonin dramatically improved survival rate of rats when compared with the I/R-only group. After 1-hr reperfusion, melatonin caused a significant reduction in infarct size when compared with I/R-only group. Meanwhile, pretreatment with melatonin (1.0 mg/kg) significantly reduced superoxide anion production and myeloperoxidase activity; the latter is an index of neutrophil infiltration in the ischemic myocardium. Additionally, pretreatment with melatonin (1.0 and 5.0 mg/kg) significantly attenuated ventricular arrhythmias and mortality elicited by reperfusion following 5-min ischemia. In conclusion, melatonin suppresses ischemia- and reperfusion-induced ventricular arrhythmias and reduces infarct size resulting from I/R injury. The pronounced cardioprotective activity of melatonin may be mediated by its antioxidant activity and by its capacity for neutrophil inhibition in myocardial I/R.     

The duration of coronary occlusion influences adrenergic contributions to reperfusion ventricular arrhythmias

Summary To study the role of the adrenergic nervous system in the genesis of nonlethal reperfusion arrhythmias, the proximal left anterior descending coronary artery was occluded for either 1 or 3 hours in 48 open-chest dogs anesthetized with alpha-chloralose. Heart rate was controlled (90 to 110 beats/min) by bilateral vagotomy and continuous right vagal stimulation. Dogs were treated with either saline, timolol (0.1 mg/kg), or prazosin (0.5 mg/kg) 15 minutes prior to reperfusion. Reperfusion after 1 hour of occlusion in saline-treated dogs evoked sustained polymorphic ventricular tachycardia (204±9 beats/min) that reverted to sinus rhythm by 15 minutes of reperfusion. The maximum rate of ventricular tachycardia was significantly reduced by both prazosin and timolol. Both drugs also caused about a 50% reduction in the total number of ectopic beats in the first 10 minutes of reperfusion. With a 3-hour occlusion, reperfusion in saline-treated dogs caused sustained polymorphic ventricular tachycardia (135±15 beats/min) which persisted for several hours. Neither timolol nor prazosin significantly altered the ventricular ectopic rate in these dogs. Furthermore, bilateral stellate transection, left stellate stimulation, isoproterenol (0.5 mg/kg), or methoxamine (100 ug/kg) all failed to alter the ventricular ectopic rate in the saline-treated dogs. Ventricular ectopy induced by reperfusion after a 1- or 3-hour occlusion was overdriven in all dogs by rapid atrial pacing. The results suggest that the nature of reperfusion-induced ventricular ectopy is highly dependent upon the preceeding duration of coronary occlusion. Whereas both alpha-1- and beta-adrenergic receptors appear to play an important role in the genesis of reperfusion-induced ectopy after a 1-hour occlusion, these receptors have little influence on reperfusion-induced ectopy after a 3-hour occlusion.