Cerebral ischemia revisited: New insights as revealed using in vitro brain slice preparations

Summary The elucidation of the pathophysiological mechanisms of cerebral ischemia/hypoxia dictates the use of experimental models which mimic this disabling brain condition. In vivo experimental models have been available for many decades and are responsible for the bulk of, though incomplete, knowledge we have about these mechanisms. Since study in isolation of each postulated mechanism is impossible in vivo, the need for an in vitro experimental model has intensified in recent years. Consequently, rat and guinea pig hippocampal slice preparations have emerged as the models of choice. This review attempts to highlight some of the results obtained using brain slices in the study of cerebral ischemia/hypoxia and compare them to those obtained in vivo. Both the biochemical and the physiological correlates of energy metabolism, ion homeostasis, neurotransmission and neuromodulation of this brain condition are reviewed. The agreements, and especially the disagreements, between the in vivo and in vitro findings are emphasized. Details are given of the possible roles of both lactic acid, Ca²⁺ and excitotoxins in the neuronal damage inflicted by cerebral ischemia/hypoxia. Recent attempts to protect brain slices against experimental cerebral ischemic/hypoxic damage are also reviewed here briefly.     

Conduction of the impulse in the ischemic myocardium — implications for malignant ventricular arrhythmias

Summary Ventricular arrhythmias occurring consequent to regional disturbances of myocardial perfusion are the most frequent cause of sudden cardiac death. They are related to marked changes of impulse propagation in the ischemic region, which consist of circulating excitation with re-entry. Mapping of the impulse during ventricular tachycardias and ventricular fibrillation shows that the circus movements change their shape and localization from beat to beat. Zones of tissue which block the impulse during one beat may conduct the impulse at a fast rate during the next beat. The main cause underlying this behavior is the depression of the ischemic action potential. This depression is caused by the partial inactivation and the prolonged recovery of the rapid sodium inward current. In addition to the decrease in resting potential, other factors, such as acidosis, contribute to the inactivation of the inward currents generating the upstroke of the action potential. An increase of coupling resistance between myocardial cells and/or an increase of extracellular resistance appear to be less important for explaining conduction disturbances in acute ischemia.     

Ventricular fibrillation threshold during acute ischemia in hypertrophied rat hearts

Summary Ventricular fibrillation threshold was significantly lower in hypertrophied hearts than in normal hearts. Ischemia produced by coronary occlusion reduced fibrillation threshold in both normal and hypertrophied hearts, but the maximum reduction in fibrillation theshold was observed earlier in hypertrophied hearts.     

Postischemic ATP levels predict hepatic function 24 hours following ischemia in the rat

Summary Hepatic function was assessed by the aminopyrine breath test (ABT) in male Sprague Dawley rats 24 h after partial hepatic ischemia. ABT decreased progressively to 26.3 (p<0.05) and 19.7% of dose (p<0.05) after 90 and 120 min of ischemia, respectively. ABT at 24 h after injury was correlated to the concentration of ATP in the ischemic lobes 1 h after the onset of reperfusion (r²=0.971) but not to ALT activity in plasma at 1 h (r²=0.391). We conclude that postischemic ATP levels are a better index of subsequent hepatic function than ALT.     

利用灌注技术观察昆明小鼠Willis环的形态结构

目的建立完整的昆明小鼠动脉环(Willis环)形态结构。方法选用昆明小鼠利用灌注技术经左心室往脑血管内灌注填充塑化剂约2 mL,去骨取脑,观察Willis环结构。结果该方法使复杂的小鼠脑血管及Willis环立体清晰的显露出来。结论我们采用灌注技术显示小鼠脑血管动脉环的形态结构,对小鼠脑血管的模型制作具有一定的指导意义。     

局灶性脑缺血再灌注损伤神经细胞凋亡的研究

目的研究局灶性脑缺血再灌注损伤后神经细胞凋亡及其大鼠脑组织不同时间病理学改变情况.方法随机选取66只成年Wistatr大鼠,按照随机数字法分3组,对照组(假手术组,n=6)、观察1组(脑缺血组,n=24)、观察2组(脑缺血再灌注组,n=36).采用线栓法制造大鼠局灶性脑缺血再灌注模型,手术后HE染色,并分别采用TUNEL法和电镜观察大鼠缺血灌注损伤后神经元凋亡情况和细胞凋亡形态的变化.结果大鼠缺血再灌注后0~63 h时其神经功能损伤最为严重,伴随时间的延长逐渐能得到轻微缓解和改善,再灌注24 h后神经功能明显好转,之后再次出现加重的趋势.研究发现:再灌注后神经元会出现凋亡,TUNEL阳性细胞集中在灌注后病灶中心的边缘区域以及皮层区.结论线栓法制备动物脑组织缺血灌注模型能有效用于脑组织缺血再灌注后的临床分析,局灶区的神经元以凋亡、坏死为主,其中轻度脑缺血主要以神经凋亡为主,中重度缺血主要以坏死为主.     

冬眠动物达乌尔黄鼠离体心脏对缺灌和再灌损伤的耐受性

秋季未入眠之达乌尔黄鼠离体心脏用Langendorff方法灌流,平衡10min,全心缺灌15min,然后再灌10min。于缺灌期和再灌期分别定时收集心脏冠脉流出液,测定流份中肌酸激酶(CK)的活性(U·L^－1),同时记录心电图和心脏收缩力。此外,用恒温动物大鼠作为冬眠动物黄鼠的实验对照,经受完全相同的实验处理。缺灌15 min期内,两种动物心脏皆有大量CK释放,释放量与缺灌时间呈线性关系。但黄鼠各采样点CK释放值都低于大鼠,提示黄鼠心脏对缺灌损伤的耐受性强于大鼠。再灌期大鼠心脏有两个CK释放峰,而黄鼠仅有第Ⅰ峰,且其活性值(179±32U·L^－1)显著低于大鼠(255±17 U·L^－1,P<0.05)。再灌期黄鼠室颤和室速发生率以及心脏收缩幅度下降百分率皆显著低于大鼠(P<0.01)。上述结果证明,与大鼠相比较,冬眠动物黄鼠心脏对缺灌和再灌损伤具有较强的耐受性。     

缺血区心肌血管网阻抗和顺应性时相变化的建模与仿真研究

为研究缺血程度和在舒张期提高灌注压对缺血区血管网阻抗和顺应性时相变化的影响,利用一个包括正常心肌和缺血心肌的左心室壁血流灌注计算机仿真模型,6条雄性犬的左心室压和主动脉压的实测数据作为输入进行仿真．结果表明,缺血区血管网中各单元阻抗和顺应性随缺血程度的加重而上升;体外反搏对阻抗和顺应性的作用与缺血程度降低一致．     

脑缺血损伤的研究进展

缺血性脑血管疾病是一种致死致残的常见病、多发病. 近年来,对脑缺血再灌注损伤的研究越来越深入. 大量的实验研究表明,脑缺血再灌注损伤对脑损害的机制是非常复杂的,在缺血性损伤过程中除缺氧和能量代谢衰竭外,由缺血诱导的一系列瀑布样效应是导致缺血性神经元死亡的重要机制. 同时脑缺血损伤的研究受到很多因素的影响,诸如血糖浓度、脑温、脑血流量、血压、鼠种以及大鼠的性别等. 本文就脑缺血损伤的相关病理生理机制、影响因素及治疗等方面的进展进行综述,以期对缺血后神经元的死亡机制作进一步的探索.     

脑缺血动物模型的研究进展

缺血性脑血管病是由于脑动脉硬化等原因,使脑动脉管腔狭窄,血流减少或完全阻塞,脑部血液循环障碍,脑组织受损而发生的一系列症状,是临床医学的难题.制备脑缺血动物模型对缺血性脑学管病的病理生理学机制的探讨、特效药的筛选、最佳治疗方法的建立就显得尤为重要,本文就常用的脑缺血动物模型的选择、制备及影响因素做一综述.