MODELING EFFECTS OF PH & MEMBRANE POTENTIALS ON CHARGED SOLUTES

PH 的模拟效果

• 批准号: 6280749
• 负责人: KEITH KROLL
• 金额: --
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-18 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6280749
• 关键词: bioengineering /biomedical engineering; biomedical resource; model design /development; technology /technique

The purpose of this study was to investigate the potential for estimating the change in mitochondrial proton motive force (PMF) by modeling the tracer kinetics of a lipophilic cation, Tc-99m-methoxyisobutylisonitrile (MIBI), using a multicapillary distributed model. Isolated working rat hearts were perfused with Krebs-Ringer Buffer containing Tl and MIBI under normoxic (540 Torr) (n=14) or hypoxic conditions (85 Torr) (n=6) for 30 min and then switched to a tracer free perfusate for 30 min. Timed coronary sinus (CS), interstitial fluid (ISF), and aortic perfusate samples were collected and tracer concentration determined. The ISF and CS tracer curves were fitted using a 4 region, 3 barrier blood-tissue exchange model, in order to estimate permeability-surface (PS) area products for capillary (PSc), myocyte (PSpc), and mitochondria (PSm), and volumes of distribution of the myocyte (Vpc) and mitochondrial (Vm) regions. Vm for the lipophilic cation MIBI is related to the mitochondrial membrane potential via the Nernst equation as is Vpc and the sarcolemmal membrane potential. mean + sd; * = p < 0.05 vs Tl; # = p < 0.05 vs normoxic Tracer PSc PSpc PSm Vpc Vm Normoxic Tl 3.45 + 1.05 6.76 + 6.41 1.12 + 2.53 3.92 + 1.23 3.10 + 2.56 Normoxic MIBI 0.34 + 0.23* 5.60 + 6.09 1.67 + 1.93 6.05 + 5.19 67.23 + 11.75* Hypoxic Tl 2.43 + 1.25 7.00 + 4.60 1.47 + 3.20 3.62 + 2.36 7.39 + 4.52# Hypoxic MIBI 0.22 2.94 + 2.61* 4.60 + 10.0 2.84 + 3.25 51.65 + 13.80*# +0.27* We conclude the estimated large PMF (Vm) for MIBI, relative to Tl, is consistent with reported mechanisms of MIBI uptake (lipophilic cation). The decreased Vm for MIBI during hypoxia is consistent with a decrease in PMF.

这项研究的目的是调查潜在的 估计线粒体质子动力（PMF）的变化 模拟亲脂性阳离子的示踪动力学， Tc-99m-甲氧基异丁基异腈 (MIBI)，使用多毛细管 分布式模型。 离体工作大鼠心脏灌注 常氧 (540 Torr) 下含有 Tl 和 MIBI 的 Krebs-Ringer 缓冲液 (n=14) 或缺氧条件 (85 Torr) (n=6) 30 分钟，然后 切换至无示踪剂灌注液 30 分钟。 定时冠状窦 (CS)、间质液 (ISF) 和主动脉灌注液样本 收集并测定示踪剂浓度。 ISF 和 CS 追踪器 使用 4 个区域、3 个屏障的血液组织交换拟合曲线 模型，以估计渗透率-表面积 (PS) 面积乘积 对于毛细血管 (PSc)、肌细胞 (PSpc) 和线粒体 (PSm)，以及 肌细胞 (Vpc) 和线粒体 (Vm) 的分布体积 地区。 亲脂性阳离子 MIBI 的 Vm 与 通过 Nernst 方程计算线粒体膜电位，Vpc 和 肌膜电位。 平均值+标准差； * = p < 0.05 与 Tl 相比； # = p < 0.05 vs 常氧示踪剂 PSc PSpc PSm Vpc Vm 常氧 Tl 3.45 + 1.05 6.76 + 6.41 1.12 + 2.53 3.92 + 1.23 3.10 + 2.56 常氧 MIBI 0.34 + 0.23* 5.60 + 6.09 1.67 + 1.93 6.05 + 5.19 67.23 + 11.75* 缺氧 Tl 2.43 + 1.25 7.00 + 4.60 1.47 + 3.20 3.62 + 2.36 7.39 + 4.52# 低氧 MIBI 0.22 2.94 + 2.61* 4.60 + 10.0 2.84 + 3.25 51.65 + 13.80*# +0.27* 我们得出 MIBI 的估计大 PMF (Vm)， 相对于 Tl，与报道的 MIBI 摄取机制一致 （亲脂性阳离子）。 缺氧期间 MIBI 降低的 Vm 为 与 PMF 的降低一致。