缩醛基毛冬青提取化合物R4对缺血缺氧心肌的保护作用

目的：研究缩醛基毛冬青提取化合物R4对缺血缺氧心肌的保护作用,以便为缩醛基毛冬青提取化合物R4的临床新用途提供实验依据。方法：采用小鼠常压耐缺氧实验、夹闭气管小鼠心电消失时间、垂体后叶素所致大鼠心肌缺血模型及大鼠冠脉结扎所致的心肌缺血模型,观察缩醛基毛冬青提取化合物R4对缺血缺氧心肌的保护作用。结果：缩醛基毛冬青提取化合物R4（1.0、2.0、4.0 mg/kg）均能显著延长小鼠常压耐缺氧条件下的存活时间,延长夹闭气管小鼠心电消失时间,缩醛基毛冬青提取化合物R4（0.75、1.5和3.0 mg/kg）能拮抗垂体后叶素引起的心电图变化,并能明显降低结扎冠脉所致大鼠的心肌梗塞范围。结论：缩醛基毛冬青提取化合物R4对缺血缺氧心肌具有明显保护作用,其效应与剂量呈相关性,其机制可能是通过扩张冠脉,增加心肌的供血供氧而发挥抗心肌缺血的作用。     

Redistribution of myocardial blood flow in chronic ischemia under the effects of pharmacological agents

In the experiments with anesthetized dogs under chronic myocardial ischemia the effect of propranolol, diltiazem, lithium and sodium hydroxybutyrate on the myocardial blood flow redistribution was studied with the help of ultrasonic method. The redistribution was estimated by the ratio change of blood flows in veins which drain blood directly from the focus of myocardial ischemia and total myocardial of left ventricular (v cardiac magna). It was established that propranolol increases the ratio and diltiazem decreases it. Some differences in the effect of antihypoxic drugs were revealed. Sodium hydroxybutyrate redistributed the blood flow in favour of the focus of myocardial ischemia and lithium hydroxybutyrate increased the blood flow both in the focus of myocardial ischemia and in the conditionally-intact region of myocardium of left ventricular.     

Effects of lipoic acid on citrate content, aconitate hydratase activity, and oxidative status during myocardial ischemia in rats

The effects of lipoic acid on intensity of free radical reactions, citrate content, and aconitate hydratase during myocardial ischemia have been investigated. Treatment with lipoic acid normalized biochemiluminescence parameters and citrate level, which were increased in the myocardial pathology. Treatment with lipoic acid also increased specific activity of aconitate hydratase, which was decreased in myocardium and blood of animals with myocardial ischemia. Administration of lipoic acid decreased DNA fragmentation observed during myocardial ischemia. The data suggest that lipoic acid can be effectively used as a cardioprotector preventing the development of free radical oxidation during myocardial ischemia.     

硫化氢对急性心肌缺血大鼠心肌线粒体损伤的影响

目的：探讨硫化氢（H2S）对急性心肌缺血大鼠线粒体功能的影响,并探讨其改善急性心肌缺血损伤的作用机制。方法：通过结扎大鼠左冠状动脉前降支建立急性心肌缺血模型。雄性SD大鼠48只随机分为6组（n=8）：假手术组,缺血组,缺血＋硫氢化钠（NaHS）低、中、高剂量组和缺血＋炔丙基甘氨酸（PPG）组。透射电镜观察心肌组织线粒体超微结构;检测血浆中H2S含量、心肌组织CSE活性;测定心肌线粒体活力、膜肿胀度及线粒体总ATP酶、谷胱甘肽过氧化物酶（GSH-PX）、超氧化物歧化酶（SOD）的活性和丙二醛（MDA）含量。结果：与假手术组比较,缺血组大鼠血浆H2S含量和心肌组织中CSE活性降低;心肌线粒体膜肿胀,线粒体活力下降;线粒体中MDA含量明显升高,ATP酶、SOD、GSH-Px活性明显降低（P〈0.01）。与缺血组比较,缺血＋NaHS低、中、高剂量组大鼠血浆H2S含量和心组织中CSE活性均升高;缺血＋NaHS中、高剂量组大鼠心肌线粒体MDA含量明显减少,膜肿胀度减轻;缺血＋NaHS低、中、高剂量组线粒体活力有所恢复,ATP酶、SOD、GSH-Px的活性明显升高（P〈0.05或P〈0.01）。PPG可部分减弱H2S的心肌保护作用（P〈0.05或P〈0.01）。结论：H2S可增强线粒体ATP酶、SOD、GSH-Px的活性,降低线粒体脂质过氧化水平,从而起到对大鼠急性心肌缺血的保护作用。     

Role of the locus coeruleus in the development of cerebrovascular disorders in acute myocardial ischemia

Experiments on rats were made to examine the total cerebral blood flow during locus coeruleus (LC) stimulation, acute myocardial ischemia and in the presence of acute myocardial ischemia after LC precoagulation . LC electric stimulation caused a decrease in the cerebral blood flow. The most profound cerebrovascular disorders were observed in animals with acute myocardial ischemia without LC precoagulation and were followed by cardiac arrhythmias. Cerebrovascular hemodynamic disorders occurring in acute myocardial ischemia were prevented by LC coagulation. It is suggested that the cerebrovascular disorders are consequent on the formation in the LC of the hyperactive determinant structure and play a role of a secondary pathogenetic factor in heart regulation disorders.     

缺血预处理对缺血/再灌注离体心脏的保护作用

目的：探讨连续多次短暂缺血预处理对缺血/再灌注损伤心肌的保护作用及机制。方法：采用大鼠离体心脏Lan-gendorff灌流模型,观察缺血预处理对心肌缺血/再灌注后不同时间点冠脉流出液中AST、CPK、UDH及冠脉流量,心肌组织中SOD、LPO以及再灌注性心律失常的影响。结果：缺血预处理可以减少缺血/再灌注损伤的心肌冠脉流出液中AST、CPK、LDH的含量,提高心肌SOD活性,降低LPO水平,并且抑制再灌注性心律失常的发生,提高再灌注期间的冠脉流量。结论：缺血预处理对心肌缺血/再灌注损伤具有一定保护作用。     

Myocardial infarction and heart failure in the db/db diabetic mouse

Clinical studies have reported that the incidence and severity of myocardial infarction is significantly greater in diabetics compared with nondiabetics after correction for all other risk factors. The majority of studies investigating the pathophysiology of myocardial ischemia-reperfusion injury have focused on otherwise healthy animals. At present, there is a paucity of experimental investigations on the pathophysiology of heart failure in diabetic animals. We hypothesized that the severity of myocardial reperfusion injury and the development of congestive heart failure would be markedly enhanced in the db/db diabetic mouse. Accordingly, we studied the effects of varying durations of in vivo myocardial ischemia and reperfusion on the incidence of heart failure in db/db diabetic mice. Nondiabetic and db/db diabetic mice (10 wk of age) were subjected to 30, 45, or 60 min of left coronary artery occlusion and 28 days of reperfusion. Survival at 24 h of reperfusion was 100% in nondiabetic mice subjected to 30 min of myocardial ischemia and 88% in nondiabetic mice subjected to 45 min of myocardial ischemia. In contrast, survival was 53% in db/db diabetic mice subjected to 30 min of myocardial ischemia and 44% in db/db mice after 45 min of myocardial ischemia. Prolonged survival in nondiabetic mice was not significantly attenuated when compared during the 28-day follow-up period with all groups experiencing >90% survival. Prolonged survival was significantly decreased in db/db mice after both 30 and 45 min of myocardial ischemia compared with sham controls. Furthermore, we observed a significant degree or left ventricular dilatation, cardiac hypertrophy, and cardiac contractile dysfunction in db/db mice subjected to 45 min of myocardial ischemia and 28 days reperfusion. In nondiabetic mice subjected to 45 min of myocardial ischemia, we failed to observe any changes in left ventricular dimensions or fractional shortening. These studies provide a feasible experimental model system for the investigation of heart failure secondary to acute myocardial infarction in the db/db diabetic mouse.     

Fibrinolytic activity of rat blood during transient coronary insufficiency

Local 10-min and 40-min myocardial ischemia was accompanied by a significant depression in the rat blood fibrinolytic activity. During 40-min postischemic myocardial reperfusion after short-term (10-min) myocardial ischemia fibrinolytic reactions were activated and after prolonged (40-min) myocardial ischemia they were suppressed.     

Cardioprotective mechanisms activated in response to myocardial ischemia

Myocardial ischemia, a disorder causing myocardial infarction and malfunction, can activate various adaptive mechanisms that protect cardiomyocytes from ischemic injury. During the early hours post myocardial ischemia, injured cardiac cells can release several molecules, including adenosine, opioids, and bradykinin, which promote myocardial survival by activating the G protein signaling pathways. During a later phase about several days, myocardial ischemia induces upregulation of growth factors and cytokines, including VEGF, ILGF, HGF, and SDF-1, in the injured myocardium, contributing to cardioprotection. In addition to the injured heart, the liver participates in cardioprotection. In response to myocardial ischemia, the liver upregulates and releases secretory proteins, including FGF21 and TFF3, both of which promote cardiomyocyte survival. The liver also provides a reservoir of hepatic cells that mobilize to the site of myocardial ischemia, potentially contributing to cardioprotection. Taken together, the early and late mechanisms act coordinately in a time-dependent manner, ensuring effective cardioprotection post myocardial infarction. Investigations on these innate cardioprotective mechanisms have provided insights into the development of cardioprotective strategies for treating myocardial infarction. In this article, the authors review the innate mechanisms of cardioprotection in myocardial ischemia.     

心肌缺血／再灌注损伤后血清和心肌组织Leptin水平的变能

目的：观察大鼠心肌缺血／再灌注损伤对血清和心肌组织瘦素（Leptin）表达的影响,探讨Leptin在心肌缺血／再灌注损伤中的作用。方法：建立大鼠心肌缺血／再灌注模型,检测血清乳酸脱氢酶（LDH）和Leptin浓度,并用HE染色和免疫组织化学观察心肌组织病理学及Lepfin表达水平。结果：缺血组、再灌注组血清LDH水平显著升高（P〈0．05）,表明该模型制作成功,造成心肌局部一定程度的损伤。缺血组血清Leptin含量（6．34±2．49）ng／ml显著低于对照组（7．50±2．93ng／ml,P〈0．05）;再灌注后Leptin水平缓慢恢复,于再灌注2h时Leptin达到（8．32±1．74）ng／ml,恢复到损伤前水平（8．38±2．56）ng／ml,且随再灌注时间延长有升高趋势。免疫纽化显示与假手术纽心肌Leptin蛋白表达水平相比,其他四组均有显著降低（P〈0．01）,按缺血45min后再灌注1h组、缺血45min后再灌注3h组、单纯缺血45min组、缺血45min后再灌注2h组依次递减。结论：Leptin在心肌缺血／再灌注损伤后早期45min血中有明显减少,心肌组织中也明显表达下降。心肌组织病理损伤与Leptin的改变可能有一定的关系。     

Shape identification of electrocardiographic ST segment based on radial basis function neural network

The types of myocardial ischemia can be revealed by electrocardiographic (ECG) ST segment.Effective measurement and electrocardiographic analysis of ST as well as calculation of displacement and shape change of ST segment can help doctors diagnose coronary heart disease and myocardial ischemia,especially for asymptomatic myocardial ischemia.Therefore,it is a very important subject in clinical practice to measure and classify the ECG ST segment.In this paper,we introduce a computerized automatic identification method of the electrocardiographic ST segment shape with radial basis function neural network based on adaptive fuzzy system,which has a better effect than other methods.It helps to analyze the reason of the ST segment change and confirm the position of myocardial ischemia,and is useful for doctor diagnosis.     

Myocardial ischemia--association with perioperative cardiac morbidity.

The development of ambulatory electrocardiographic recorders and analysers and the application of transesophageal echocardiography in the mid-1980''s enabled investigators to quantify and describe the occurrence of silent as well as symptomatic ischemia in the perioperative period. Several technical advances which have recently occurred in ECG monitoring include the use of miniaturized digital computing equipment to store and analyze data. In addition, real time ST-segment analysis has become widely available on multicomponent monitors in both the operating room and intensive care units. The incidence of perioperative myocardial ischemia depends on the patient population, the surgical procedure, and the monitoring technique used. Several studies in the early 1990''s have shown that cardiac morbidity in patients undergoing major, noncardiac surgery is best predicted by postoperative myocardial ischemia, rather than tradition preoperative clinical predictors. Long duration postoperative ischemia may be the factor most significantly associated with adverse cardiac outcome. Postoperative pain, physiological and emotional stress may all combine to cause tachycardia, hypertension, increase in cardiac output, and fluid shifts which, in high risk patients, might result in subendocardial ischemia and eventual myocardial infarction. If postoperative myocardial ischemia is the cause of late postoperative myocardial infarction in patients undergoing non-cardiac surgery, then treatment of postoperative myocardial ischemia should reduce morbidity. In addition, reducing pain and stress and avoiding postoperative hypoxemia might prevent postoperative myocardial ischemia and minimize the need for extensive preoperative cardiac evaluation.     

Effect of parathyroidin on the course of acute myocardial ischemia in experiments on rats

Experiments were made on 187 white rats weighing 180-200 g. Acute myocardial ischemia was simulated in 137 animals. Fifty sham-operated rats served as control. Experimental acute myocardial ischemia was accompanied by an increase in blood creatine phosphokinase and lactate dehydrogenase activity as well as by an elevation of serum lactate level and fall of blood plasma calcium concentration, suppression of diuresis and excretion of calcium with urine. Intraperitoneal injections of parathyroidine to rats with acute myocardial ischemia led to rapid normalization of the homeostatic parameters. Lethality of experimental animals decreased 1.8-fold.     

参附注射液对心肌缺血/再灌注损伤血流动力学和心肌酶的影响

目的：探讨参附注射液对家兔心肌缺血/再灌注（I/R）损伤的保护作用及其机制。方法：家兔30只,随机分为3组（n=10）：对照组、心肌缺血/再灌注损伤（MI/RI）组和参附注射液组,统一标准喂养。行药物预处理10 min后,手术结扎家兔冠状动脉左心室支,建立急性心肌缺血再灌注模型,观察急性心肌缺血和再灌注状态下血流动力学及心肌组织中酶的变化。结果：与对照组比较：MI/RI组心脏舒缩功能减退,丙二醛（MDA）含量增高,超氧化物歧化酶（SOD）、谷光甘肽过氧化物酶（GSH-PX）和细胞能源Na＋-K＋-ATP酶及Ca2＋-ATP酶活性降低,乳酸脱氢酶（LDH）、肌酸激酶（CK）大量释放。而与MI/RI组比较：参附注射液组能不同程度的恢复左心室收缩压（LVSP）、心室内压最大变化速率（±dp/dtmax）（P〈0.01）,降低左室舒张末期压（LVEDP）（P〈0.01）,抑制MDA、LDH、CK升高,增强SOD、GSH-PX、Na＋,K＋-ATP及Ca2＋-ATP活力。结论：参附注射液对心肌缺血/再灌注损伤具有明显的保护作用。     

基因治疗心肌缺血的载体应用新进展

近年来,随着基因治疗技术的不断进步,为心肌缺血的治疗开辟了一条全新的途径,并取得了一些令人鼓舞的进展。基因治疗主要包括治疗基因、基因转移载体以及基因导入途径三个方面。基因转移载体又在治疗基因和基因表达之间起着桥梁作用,因此,发展安全、高效的基因转移系统是基因治疗的关键之一。目前用于基因治疗心肌缺血基因转移的载体主要有病毒载体和非病毒载体。下面将就不同载体在心肌缺血的基因治疗中的应用进展进行简要的总结。     

雷米普利对糖尿病大鼠心肌缺血／再灌注损伤保护作用的超微结构研究

目的：研究雷米普利对糖尿病大鼠心肌缺血／再灌注损伤的保护作用,并从超微结构的角度初步探讨其作用机制。方法：链脲佐菌素致糖尿病大鼠被随机分为3组（n=16）：缺血／再灌注（I／R）、缺血预适应（IPC）和雷米普利（RAM）组。RAM组每天用雷米普利（1mg／kg）灌胃,I／R和IPC组用等体积生理盐水灌胃。4周后各组动物均经历心肌缺血／再灌注损伤,IPC组于缺血前行心肌缺血预适应。连续监测心电图变化,测定心肌梗死面积,光、电镜下观察心肌形态学改变。结果：与I／R组比较,RAM及IPC组缺血期心脏ST-段抬高幅度降低,室早出现时间推迟,持续时间缩短,室速、室颤发生率降低,心肌梗死面积缩小,形态学观察心肌损伤减轻,心肌纤维及线粒体特征性结构保持清晰,血管通畅,内皮损伤减轻。结论：连续4周使用RAM对实验性糖尿病大鼠具有与IPC相似的心脏保护效应,机制可能与保护心肌细胞及线粒体、改善内皮功能等有关。     

基因治疗心肌缺血的载体应用新进展

近年来,随着基因治疗技术的不断进步,为心肌缺血的治疗开辟了一条全新的途径,并取得了一些令人鼓舞的进展。基因治疗主要包括治疗基因、基因转移载体以及基因导入途径三个方面。基因转移载体又在治疗基因和基因表达之间起着桥梁作用,因此,发展安全、高效的基因转移系统是基因治疗的关键之一。目前用于基因治疗心肌缺血基因转移的载体主要有病毒载体和非病毒载体。下面将就不同载体在心肌缺血的基因治疗中的应用进展进行简要的总结。     

Effect of NO synthase inhibition on myocardial metabolism during moderate ischemia

Nitric oxide (NO) is involved in the control of myocardial metabolism. In normoperfused myocardium, NO synthase inhibition shifts myocardial metabolism from free fatty acid (FFA) toward carbohydrate utilization. Ischemic myocardium is characterized by a similar shift toward preferential carbohydrate utilization, although NO synthesis is increased. The importance of NO for myocardial metabolism during ischemia has not been analyzed in detail. We therefore assessed the influence of NO synthase inhibition with N(G)-nitro-l-arginine (l-NNA) on myocardial metabolism during moderate ischemia in anesthetized pigs. In control animals, the increase in left ventricular pressure with l-NNA was mimicked by aortic constriction. Before ischemia, l-NNA decreased myocardial FFA consumption (MV(FFA); P < 0.05), while consumption of carbohydrate and O(2) (MVo(2)) remained constant. ATP equivalents [calculated with the assumption of complete oxidative substrate decomposition (ATP(eq))] decreased with l-NNA (P < 0.05), associated with a decrease of regional myocardial function (P < 0.05). In contrast, aortic constriction had no effect on MV(FFA), while MVo(2) increased (P < 0.05) and ATP(eq) and regional myocardial function remained constant. During ischemia, alterations in myocardial metabolism were similar in control and l-NNA-treated animals: MV(FFA) decreased (P < 0.05) and net lactate consumption was reversed to net lactate production (P < 0.05). Regional myocardial function was decreased (P < 0.05), although more markedly in animals receiving l-NNA (P < 0.05). We conclude that the efficiency of oxidative metabolism was impaired by l-NNA per se, paralleled by impaired regional myocardial function. During ischemia, l-NNA had no effect on myocardial substrate consumption, indicating that NO synthases were no longer effectively involved in the control of myocardial metabolism.     

Oxygen radicals in cardiac surgery

Most cardiac surgical procedures require the use of prolonged induced myocardial ischemia. Experimental models of global myocardial ischemia which mimic cardiac surgical techniques have been developed to investigate the possibility of oxygen free radical development during prolonged myocardial ischemia or upon reperfusion. In such experiments, various free radical scavenging agents, including superoxide dismutase, catalase, and mannitol, have been shown to improve the tolerance of the heart to protracted global ischemia. Use of these agents has improved cardiac functional recovery and has attenuated the biochemical and structural changes which occur due to prolonged ischemia and reflow. In a recently developed porcine experimental model, the effects of preexisting regional myocardial ischemia with superimposed global ischemia and reperfusion have been studied, with free radical scavenging agents administered in an attempt to reduce myocardial infarction and improve regional functional recovery. In most such studies completed to date, free radical scavenging agents have resulted in better myocardial preservation, suggesting, at least indirectly, that there may be an oxygen free radical-mediated component of the ischemia-reperfusion injury seen in such models. Techniques for directly measuring myocardial oxygen free radical levels may allow for early clarification of the development of such toxic species in the clinical cardiac surgical setting.