METABOLIC INTERVENTIONS FOR PRESERVING TRANSPLANTED LUNG

保护移植肺的代谢干预措施

• 批准号: 6335263
• 负责人: DAN M MEYER
• 金额: $ 0.7万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-15 至 2001-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6335263
• 关键词: Mammalia; animal tissue; biological products; biomedical resource; cardiovascular system; injury; minerals; nuclear magnetic resonance spectroscopy; technology /technique

In the past year, we have used 19F NMR for the measurement of cytosolic free calcium in perfused hearts. Initial concerns were related to the possible alterations by BAPTA of the kinetics of calcium release or sequestration. Therefore, in these studies we used a new calcium indicator with a high dissociation constant (KD) TF-BAPTA which has been shown to reduce perturbations due to buffering of transients. Our initial studies with TF-BAPTA showed minimal effects on myocardial contractility. This is a great advantage compared to studies with 5F-BAPTA which showed that developed left ventricular pressure was reduced by 80% after 30 minutes of loading. Using TF-BAPTA for cytosolic free calcium measurement in Langendorff perfused rat hearts, we showed that myocardial intracellular calcium increased five-fold 24 hours postburn; these changes in intracellular calcium were paralleled by a 46% decrease in myocardial contractile function. While the high dissociation constant of TF-BAPTA is not well suited for measuring basal intracellular calcium, our initial value of intracellular calcium was 807 nM which is close to the value measured with 5F-BAPTA (630 nM). Thus our use of TF-BAPTA in the isolated heart allows us to detect changes in the intracellular calcium levels that are mediated by burn trauma and sepsis in vivo. Thus, our studies during the past year have shown that TF-BAPTA allows effective assessment of changes in [Ca2+]i in the perfused heart in models of sepsis or burn trauma. The advantage of measuring [Ca2+]i using this technique is that we can correlate injury-mediated changes in the intracellular electrolyte concentrations with changes in mechanical performance as well as metabolic status. (Service 2) REPORT PERIOD: (09/01/97-08/31/98)

在过去的一年中，我们使用了19F NMR进行测量 灌注心脏中的无胞质钙。 最初的担忧是 与Bapta可能改变的动力学有关 钙释放或隔离。 因此，在这些研究中，我们使用了 具有高解离常数（KD）的新钙指标 TF-BAPTA已显示出由于缓冲而减少扰动 瞬态。 我们对TF-Bapta的初步研究表明很少 对心肌收缩性的影响。 这是一个很大的优势 与5F-BAPTA的研究相比，该研究表明该研究左 加载30分钟后，心室压力降低了80％。 在Langendorff中使用TF-BAPTA进行胞质免费钙测量 灌注大鼠心脏，我们表明心肌内钙 燃烧后24小时增加了五倍；这些细胞内的变化 钙与心肌收缩降低46％平行 功能。 虽然TF-BAPTA的高解离常数不是 非常适合测量基础细胞内钙，我们的初始 细胞内钙的值为807 nm，接近值 用5F型河口（630 nm）测量。 因此，我们在 孤立的心脏使我们能够检测细胞内的变化 由体内烧伤创伤和败血症介导的钙水平。 因此，过去一年的研究表明，TF-Bapta允许 有效评估灌注心脏中[Ca2+] i的变化 败血症或烧伤创伤的模型。 测量[Ca2+] i的优点 使用这种技术是我们可以将伤害介导的变化相关联 在细胞内电解质浓度中，随着变化的变化 机械性能以及代谢状态。 （服务2） 报告期限：（09/01/97-08/31/98）