ADENOSINE ENHANCED MYOCARDIAL PROTECTION DURING SURGERY

心脏手术中缺血心肌保护的现状 包括使用低温、缺血停止和化学疗法 心脏麻痹 尽管有这些干预措施， 可能发生心肌损伤。 为了进一步降低发病率 手术后心肌损伤，更好地了解 与术后心室相关的生化异常 功能障碍是必要的。 本研究的长期目标是 深入了解细胞内 ATP的区室化和心脏收缩功能 缺血和再灌注的设置。 具体而言，我们将确定： (1)如果心肌核苷酸库的恢复率可以 通过操纵内源性心脏组织腺苷水平， (a)双嘧达莫，（B）腺苷-5 'α，β亚甲基二磷酸 （c）氯-9-（2）-羟基-3-壬基腺嘌呤盐酸盐（EHNA）; (2)如果心室功能的恢复受到心室收缩率的影响， 核苷酸补充，（3）如果通过增强保留增加ATP 内源性腺苷或AMP的变化反映了 线粒体和胞质间室的细胞ATP，和（4）如果 增加的胞质ATP含量导致体内细胞内的功能改善， 狗准备。 离体Langendorff灌注等体积 收缩大鼠心脏制备物和使用 狗将被用来确定腺嘌呤核苷酸的时间变化， 池和心室功能对缺血和再灌注的反应。 将通过确定dP/dt max和 函数曲线，而核苷酸浓度将由 通过高效液相色谱法冷冻钳夹组织。 腺嘌呤核苷酸的亚细胞分布将通过 采用非水性组织分级分离技术。 分析 将采用方差和回归分析来确定差异 治疗和心室功能对ATP的依赖性。 这 这项研究可能会导致一种可能的治疗方法， 缺血发作后的恢复。

Protection of the ischemic myocardium during cardiac surgery presently involves the use of hypothermia, ischemica arrest, and chemical cardioplegia. Despite these interventions, irreversible ischemic myocardial injury may occur. In order to further decrease the incidence of myocardial damage after surgery, a better understanding of the biochemical abnormalities associated with postoperative ventricular dysfunction is needed. The long-term objectives of this study are to provide insight into the relationship between intracellular compartmentalization of ATP and cardiac contractile function in the setting of ischemia and reperfusion. Specifically, we will determine: (1) if the rate of restoration of myocardial nucleotide pool can be enhanced by manipulating endogenous cardiac tissue adenosine levels with (a) dipyridamole, (b) adenosine-5' alpha, beta methylene diphosphate (AOPCP), and (c) erythro-9-(2)-hydroxy-3-nonyladeninehydrochloride (EHNA); (2) if the recovery of ventricular function is influenced by the rate of nucleotide repletion, (3) if the increase in ATP via augmented retention of endogenous adenosine or AMP reflects a change in the distribution of cellular ATP between mitochondrial and cytosolic compartments, and (4) if increased cytosolic ATP content results in improved function in an in vivo dog preparation. An isolated, Langendorff-perfused, isovolumetrically contracting rat heart preparation and a cardiopulmonary bypass model using dogs will be employed to determine temporal changes in adenine nucleotide pools and ventricular function in response to ischemia and reperfusion. Ventricular function will be assessed by determining dP/dt max and function curves, while nucleotide concentrations will be determined from freeze clamped tissue by high performance liquid chromatography. Subcellular distribution of adenine nucleotides will be evaluated by employing a non-aqueous tissue fractionation technique. Analysis of variance and regression analysis will be employed to determine difference among treatments and dependence of ventricular function on ATP. This research could lead to a possible treatment to enhance ventricular recovery after an ischemic episode.