缺血预适应对缺血再灌注心室肌有效不应期影响的实验研究

观察２４只家兔左冠状动脉前降支（ＬＡＤ）阻闭、再通过程中心室肌有效不应期（ＥＲＰ）变化情况，以探讨缺血预适应（ＰＣ）抗缺血再灌注心律失常的部分电生理机制。２４只健康家兔，体重２．５～３．０ｋｇ，随机等分成两组。按每千克体重戊巴比妥钠３０ｍｇ剂量术前静...     

心肌缺血预适应与再灌注损伤

心肌缺血预适应现象的发现使其成为心肌缺血 再灌注损伤的一种有效的治疗措施 ,近 3 0年的基础和临床研究逐步阐明了这种现象发生的机制。本文综述了该现象研究的历史和最新进展 ,以及缺血预适应对心肌细胞、内皮细胞的保护作用 ,并阐述了其与心肌梗死、心肌顿抑和心律失常的临床关系 ,文章中也涉及到了最新的麻醉剂预适应和远隔保护作用     

兔右冠脉缺血预适应与右心缺血再灌注损伤

目的 :探讨兔右冠脉缺血预适应 (IP)与缺血再灌注损伤 (IR)的相关性。方法 :以单纯缺血 6 0 min 再灌注 6 0 min(IR)为对照 ,观察经 IP(缺血 5min 再灌注 10 min)后 IR心肌缺血型 S- T段、超微结构改变及再灌注心律失常发生率。结果 :较之 IR组 ,IP组的 ST段明显下移 ,电镜下见右室和右房心肌超微结构改变明显减轻 ,缓慢型再灌注心律失常的发生率明显减少。结论 :清醒兔右冠脉 IP可减少 IR引起的右心缺血性超微结构损伤及再灌注心律失常发生率     

非心肌组织缺血预适应及其对心脏的保护作用

缺血预适应已经从心脏扩展到心外组织如脑、视网膜、肺、胃、肝脏、小肠、肾脏、骨骼肌等，非心肌组织缺血预适应对远隔的心脏也具有保护作用。非心肌组织缺血预适应及其对心脏的保护与经典的心脏缺血预适应都属于机体内源性的保护作用，在诱导方式与作用机制方面，它们有相同之处，但也存在差异。     

优降糖对缺血预适应心肌再灌注损伤的影响

心肌缺血预适应 (IPC)对心肌具有保护作用 ,在犬、兔、猪、大鼠、人等进行的大量研究均证实了这种现象的存在 ,但IPC的作用机理迄今尚未完全阐明。本文旨在研究在完整大鼠模型中 ,IPC对心肌保护作用是否通过三磷酸腺苷 (ATP)敏感钾通道(KATP)介导。资料和方法　　 1 实验动物 :健康雄性Spraque Daley(SD)大鼠 ,体重 15 0～ 170g ,由中国医科大学实验动物部提供 ;所有大鼠均自由饮水、摄食 ,由实验动物部专人饲养。2 .实验分组和方法 :腹腔内注射戊巴比妥 (5mg/kg)进行麻醉 ,采用结扎及放松冠状动脉前降支(LAD)的方法复制心肌缺血 …     

缺血预适应研究现状及展望

缺血预适应（ischem ic precond ition ing,IPC）有强有力的保护效应,IPC现象的发现,为缺血/再灌注损伤的防治开拓了一个新的研究领域。本文对IPC的特点,各期的分子或细胞机制及其最新进展,以及IPC的临床应用前景进行探讨,并提出药物预适应可能是今后IPC临床应用的方向。     

三碘甲状腺原氨酸和缺预适应对大鼠小肠缺血再灌注损伤的作用

目的 了解缺血预适应和Ｔ３对小肠缺血再灌注损伤的作用。方法 观察缺血预适应和Ｔ３对大鼠小肠缺血再灌注后肠组织腺苷酸含量和肠粘膜损伤的影响。结果 Ｔ３组和预适应组（预适应为１０分钟缺血后１５分钟再灌注）的小肠组织ＡＴＰ及总腺苷酸含量均明显高于对照组（Ｐ〈０．０５）,肠粘膜损伤亦明显减轻;且Ｔ３组比预适应组肠粘膜损伤更轻（Ｐ〈０．０５）,动物存活率增加（Ｐ〈０．０５）。结论 Ｔ３和缺血预适应对小肠缺血     

缺血预适应与心肌细胞内钙离子的变化

缺血预适应作为心脏内源性的保护机理之一涉及细胞内多种复杂的变化。其中细胞Ca2 + 在缺血预处理期间短暂轻度升高或以启动细胞内第二信使系统 ,改变细胞内各种Ca2 + 的转运 ,减轻缺血再灌注期细胞内Ca2 + 的升高 ,产生对心脏的保护作用。在缺血预适应期及缺血再灌注期 ,细胞内Ca2 + 的变化涉及细胞膜L Ca2 + 型通道、细胞内肌浆网、线粒体及细胞膜Na+ /Ca2 + 交换等方面的变化     

缺血后适应干预缺血再灌注心肌相关信号通路的研究进展

<正> 再灌注治疗可挽救急性心肌梗死(acute myocardial infarction,AMI)濒临死亡的心肌,但随后的缺血冉灌注(ischemicreperfusion,I/R)损伤却减弱了冉灌注治疗带来的益处。作为再灌注治疗的一种辅助方法,缺血预适应可以缩小心肌梗死范围,然而必须在缺血事件发生前应用才能发挥保护心     

缝隙连接在大鼠缺血预适应心肌保护中的作用

目的探讨心肌缝隙连接在缺血预适应中的调控机制以及在预适应信号传导通路中的地位和作用。方法Sprague—Dawley大鼠进行30min的冠状动脉缺血和4h再灌注,根据是否使用缺血预适应、二氮嗪、18β-甘草次酸和5-羟基奎酸分为7组,即对照组（单纯缺血再灌注）、缺血预适应组、缺血预适应和5-羟基奎酸合用组、二氮嗪组、二氮嗪和5-羟基奎酸合用组、甘草次酸组、甘草次酸和5-羟基奎酸合用组。测量各组的血流动力学指标、心肌梗死面积以及缝隙连接蛋白43的磷酸化和内化。结果与对照组相比,缺血预适应、二氮嗪、18β-甘草次酸能降低心肌梗死面积（P〈0．001）,5-羟基奎酸可以阻断缺血预适应和二氮嗪的心肌保护作用（P〉0．05）,但是对缝隙连接失耦联剂甘草次酸没有影响（P〈0．001）。缺血预适应和线粒体三磷酸腺苷敏感性钾通道开放剂二氮嗪能促进缝隙连接蛋白43磷酸化,抑制去磷酸化和内化（P〈0．001,P〈0．001）,线粒体三磷酸腺苷敏感性钾通道阻断剂5-羟基奎酸能阻断该作用（P〉0．05,P〉0．0051）。结论缺血预适应通过开放线粒体三磷酸腺苷敏感性钾通道来调节缝隙连接蛋白43的磷酸化和内化,进而调控缝隙连接的化学转运,减少心肌梗死面积。     

大鼠脑缺血再灌注过程中血浆内皮素含量变化及分析

四血管闭塞法制备大鼠脑缺血再灌注模型，测定脑缺血再灌注过程中大鼠血浆内皮素（ＥＴ）含量。结果表明：脑缺血２０ｍｉｎ血浆ＥＴ含量较假手术组明显升高，再灌注６０ｍｉｎ后，血浆ＥＴ含量与假手术对照组相比无统计差异。故认为ＥＴ参与脑缺血期脑损害，再灌注损伤与血浆ＥＴ浓度关系不大，但与ＥＴ的生物学作用并非无关。     

L-nitro-arginine inhibits increase in endothelin binding sites induced by ischemia and reperfusion

We have demonstrated that ischemia and reperfusion promoted augmented contractile response to endothelin-1 (ET) in coronary arteries in the presence of polymorphonuclear leukocytes (PMN). It has been also reported that ischemia and reperfusion increase ET binding sites in cardiac membrane in isolated rat heart perfused by blood cell-free system. To determine the role of PMN and L-arginine to nitric oxide (NO) pathway in these phenomena, isolated perfused rabbit hearts were subjected to 30 min of global ischemia followed by 30 min of reflow in the absence or presence of PMN and 10(-5)M of L-nitro-arginine (LNA). PMN was prepared with Percoll density gradients from peritoneal exudate elicited by glycogen. PMN activated with 10(-6)M of phorbol myristate acetate or their supernatant were infused into the coronary perfusion circuit after 5 min of reflow. LNA was added to perfusate also after reflow. The effect of superoxide dismutase (SOD: 50 IU/ml) was also determined. After the end of protocols, membrane fraction was isolated from the hearts for (125)I-ET-1 binding assay. ET-1 binding (Bmax) showed a significant increase by ischemia and reperfusion (P<0.01 vs control). That was markedly augmented with addition of activated PMN or their supernatant (both P<0.01), but abolished either by LNA or SOD (P<0.01 and P<0.05, respectively). These results indicate that increase in ET-receptor by ischemia and reperfusion is mediated by free radicals generated via L-arginine to NO pathway.     

Variations in plasma endothelin concentrations during coronary spasm

A provocation test using methylergometrine was carried out inpatients with a normal coronary angiogram. Patients exhibitingspasm (Group I, n = 6) were compared with non-spasm patients(Group II, n = 6). The endothelin concentration was determinedin all cases at 0800, 1100, 1400, 1600, 1900, 2100, 2300 and0100 h. The provocation test was carried out at 1700 h and anadditional determination was made during spasm if the test waspositive. The two groups had similar clinical characteristics and didnot differ in terms of risk factors. Apart from the value recordedduring spasm, the endothelin plasma level was significantlyhigher in Group I. A time x measurement interaction was notedin both groups, with a higher endothelin level in the morning.The endothelin level increased signficantly during spasm inGroup I patients. The plasma concentration of endothelin appeared to be higherin the basal state and during spasm in patients exhibiting spasticangina.     

参麦注射液对兔心肌缺血再灌注内皮功能的影响

目的 :观察兔心肌缺血再灌注 (I/R)损伤中内皮功能改变 ,参麦注射液 (SMI)对其影响及作用机制。方法 :检测假手术对照组、心肌I/R模型组及心肌I/R加SMI治疗组 ,不同时期血中一氧化氮代谢产物 (NOP)和内皮素 (ET)含量及心肌组织NOP、ET、总超氧化物歧化酶 (T SOD)和丙二醛 (MDA)含量 ,并电镜观察心肌超微结构。结果 :I/R模型组与假手术对照组比较缺血 4 0min、再灌注 4 0min血清NOP明显降低 ,血浆ET显著增高 ;再灌注 4 0min后心肌组织NOP、T SOD明显降低 ,ET、MDA明显增高 ,心肌超微结构发生异常改变。而I/R加SMI治疗组与I/R模型组比较上述改变减轻。结论 :心肌I/R导致血管内皮功能紊乱 ;SMI能够改善I/R时的内皮功能 ,减轻心肌I/R损伤     

Effects of repeated brief episodes of ischemia and reperfusion in isolated perfused rat hearts

Summary The effects of ischemia and reperfusion on the coronary endothelium and myocardium as well as tolerance to ischemia/reperfusion injury were assessed using isolated retrogradely perfused rat hearts. Repeated brief episodes of myocardial ischemia followed by reperfusion is known to have a protective effect against subsequent myocardial infarction. However, no studies have been performed with perfusion in the absence of blood cells to determine the effect of repeated ischemia and reperfusion on the coronary endothelium and myocardium. Using the Langendorff perfusion technique, rat hearts were subjected to a 30-, 10-, 5-, or 2-min period of low-flow perfusion by reducing the coronary flow to 3ml/min followed by reperfusion at 20ml/min for the same period of time. Control perfusion was then performed at a constant flow rate of 20 ml/min for 60min. Acetylcholine-induced coronary vasodilation was significantly (P < 0.05) lower in hearts subjected to 30min of ischemia and 30min of reperfusion when compared with the control hearts. Myocardial creatinine kinase (CK) activity was significantly reduced (P < 0.01) in hearts subjected to ischemia and reperfusion for either 30, 10, or 5min. To assess the effect of repeated episodes of ischemia and reperfusion, the following protocols were used: a control study with constant perfusion for 60min (group A), 30min of ischemia and 30min of reperfusion (group B), three 10min episodes of ischemia and reperfusion (group C), six 5-min episodes of ischemia and reperfusion (group D), and 15 2-min episodes of ischemia and reperfusion (group E). Acetylcholine-induced coronary vasodilation was significantly inhibited in group B (80% ± 12%,P < 0.05) and group C (70% ± 13%,P < 0.01), but did not change significantly in either group D (123% ± 19%) or group E (142% ± 15%), compared with the control group (group A; 127% ± 15%, mean ± SEM). Nitroglycerin-induced coronary vasodilation was not altered by ischemia/reperfusion in any group. In contrast, myocardial CK activity was significantly lower in group B (3.6 ± 0.6IU/mg protein,P < 0.01), group C (3.2 ± 0.1IU/mg protein,P < 0.01), and group D (3.3 ± 0.2IU/mg protein,P < 0.01) than in group A (47 ± 6.7 IU/mg protein). The myocardial CK activity of group E was not significantly different from that of group A, but was significantly higher than in groups B, C, and D (P < 0.01). In isolated perfused rat hearts, both the coronary endothelium and myocardium are damaged by repeated episodes of ischemia and reperfusion. However, the coronary endothelium is more resistant to such damage than is the myocardium.     

Ketamine anesthesia reduces intestinal ischemia/reperfusion injury in rats

AIM： To investigate the effects of ketamine anesthesia on the motility alterations and tissue injury caused by ischemia/reperfusion in rats. METHODS： Thirty male Wistar rats weighing 200-250 g were used. Ischemia was induced by obstructing blood flow in 25% of the total small intestinal length （ileum） with a vascular clamp for 45 min, after which either 60 min or 24 h of reperfusion was allowed. Rats were either anesthetized with pento-barbital sodium （50 mg/kg） or ketamine （100 mg/kg）. Control groups received sham surgery. After 60 min of reperfusion, the intestine was examined for mor-phological alterations, and after 24 h intestinal basic electrical rhythm （BER） frequency was calculated, and intestinal transit determined in all groups. RESULTS： The intestinal mucosa in rats that were anesthetized with ketamine showed moderate alterations such as epithelial lifting, while ulceration and hemorrhage was observed in rats that received pento-barbital sodium after 60 min of reperfusion. Quantitative analysis of structural damage using the Chiu scaleshowed significantly less injury in rats that received ketamine than in rats that did not （2.35 ± 1.14 vs 4.58 ± 0.50, P 〈 0.0001）. The distance traveled by a marker, expressed as percentage of total intestinal length, in rats that received pentobarbital sodium was 20% ± 2% in comparison with 25.9% ± 1.64% in rats that received ketamine （P = 0.017）. BER was not statistically different between groups. CONCLUSION： Our results show that ketamine anesthesia is associated with diminished intestinal injury and abolishes the intestinal transit delay induced by ischemia/reperfusion.     

夹脊穴和足三里穴埋线刺激对老年大鼠不同脑区单胺类神经递质含量的影响

老年大鼠性腺内分泌及生殖功能衰退主要与下丘脑释放ＧｎＲＨ的能力下降有关。而ＧｎＲＨ释放减少又与下丘脑ＣＡ类神经递质（ＮＡ、ＤＡ）含量下降,ＣＡ／５－ＨＴ比值下降有关。在老年大鼠夹脊穴和足三里穴埋线四次,刺激４０ｄ后,用荧光法测定海马、下丘脑和中脑内５－ＨＴ、ＮＡ、ＤＡ含量。发现老年大鼠５－ＨＴ、ＤＡ、ＮＡ含量都降低,以ＮＡ、ＤＡ降低尤为明显。穴位刺激后５－ＨＴ、ＮＡ、ＤＡ含量升高,其中ＤＡ、５－ＨＴ升高显著。已知肾俞穴埋线可以不同程度激活下丘脑内侧视前区、蓝斑和中缝核神经元兴奋性,增加蓝斑对下丘脑内侧视前区激活效应,减少老年大鼠皮层、下丘脑、蓝斑中脂褐质颗粒沉积,缩短老年雌鼠性周期长度,延缓老年雄鼠性腺衰老发生。所以长期慢性刺激夹脊穴和足三里穴可通过调节脑内单胺类神经递质而产生抗衰老作用。     

Edaravone reduces mitochondrial damage due to reperfusion injury following leg ischemia in rats

PURPOSE:

Free radicals have been implicated in reperfusion injury. It was shown that the free radical scavenger edaravone might suppress reperfusion injury in rat extremities. The present study aimed to elucidate how edaravone suppresses reperfusion injury, focusing on its effect on the mitochondrial structure and glycogen storage in the lower extremity muscles.

METHODS:

Sixteen male Lewis rats (mean [± SD] weight 497±32 g) were divided into two groups and injected with either 3.0 mg/kg of edaravone (edaravone group, n=8 rats) or the same dose of saline (control group, n=8 rats) into the peritoneal cavity. The rat reperfusion injury models were created by clamping the bilateral common femoral arteries for 5 h, then declamping. The muscles were harvested more than 5 h after the start of reperfusion. The mitochondrial damage, defined as mitochondrial swelling, was examined using a transmission electron microscope at ×30,000 original magnification (n=3 for each rat). Glycogen storage, defined as a positive periodic acid-Schiff stain area, was examined using computerized densitometry (n=5 sections for each rat).

RESULTS:

The mitochondria in the control group demonstrated marked swelling (mean mitochondrial size = 0.169±0.059 μm²). However, the mitochondria in the edaravone group had significantly less swelling (mean mitochondrial size = 0.102±0.036 μm²; P<0.01). The mean percentage of positive periodic acid-Schiff stain was also significantly higher in the edaravone group than in the control group (51.7±6.8% versus 7.3±2.1%; P<0.01).

CONCLUSION:

The results suggested that edaravone reduces mitochondrial damage due to reperfusion injury, resulting in a high level of glycogen storage.     

Deterioration in myocardial blood flow following relief of sustained ischemia is not associated with release of endothelin into the coronary sinus

Summary Numerous studies have described a progressive deterioration in resting myocardial blood flow following relief of sustained ischemia in both necrotic and salvaged myocardium (termed no reflow and low reflow, respectively). We sought to determine whether release of the potent vasoconstrictor peptide endothelin-1 may play a role in these phenomena. As part of a previous study in our laboratory, 14 anesthetized open-chest dogs underwent 1 h of coronary artery occlusion and 4 h of reperfusion, while 2 dogs served as time-matched sham-operated controls (artery isolated but not occluded). Regional myocardial blood flow was measured by injection of radiolabeled microspheres at 30 min and 4 h post reflow; endothelin-1 concentrations in the coronary sinus were determined by radioimmunoassay at baseline, during coronary occlusion and at 30 min and 4 h after reperfusion; and the extent of myocardial necrosis was delineated by post-mortem tetrazolium staining. As expected, in dogs subjected to ischemia/reperfusion, regional myocardial blood flow deteriorated between 30 min and 4 h post reflow in both the subendocardium (1.40±0.30 versus 0.48±0.06 ml/min/g;p=0.003; reflecting a mixture of no reflow and low reflow) and subepicardium (0.84±0.08 versus 0.64±0.07 ml/min/g;p=0.03; due to low reflow). However, endothelin levels showed only a modest and nonsignificant increase during the protocol (4.1±0.5, 4.7±0.2 and 4.9±0.6 pg/ml plasma at baseline, 30 min and 4 h post reflow;p=NS), and regression analysis revealed no correlation between release of endothelin and deterioration in blood flow in either myocardial layer. Moreover, the sham-operated controls showed a similar modest increase in endothelin levels, with no change in myocardial perfusion during the course of the protocol. We therefore conclude that deterioration in myocardial blood flow following relief of sustained ischemia in the anesthetized open-chest dog is not associated with release of endothelin-1 into the coronary sinus.     

预处理对肝脏再灌注损伤大鼠肝组织、血液中NO和ET的影响及意义

目的　探讨预处理对肝脏缺血再灌注损伤大鼠肝组织和血液中一氧化氮 (NO)和内皮素 (ET)含量的影响及意义。方法　建立肝脏 70 %缺血再灌注损伤大鼠模型 ,分为对照组、缺血组、缺血预处理组、L -精氨酸组(L - arg)、Nω-硝基 - N -精氨酸甲酯 (L - NAME)组 ,观察各组肝功能变化 ,检测肝组织和血清中 NO和 ET及透明质酸 (HA)水平。结果　预处理可减轻 NO水平的下降和血浆 ET的升高 ,防止肝功酶的升高 (P<0 .0 5 )。结论　预处理可诱导缺血再灌注损伤大鼠 NO产生增加、ET产生减少 ,进而改善其微循环 ,减少再灌注损伤。