MODELING EFFECTS OF PH & MEMBRANE POTENTIALS ON CHARGED SOLUTES

PH 的模拟效果

• 批准号: 6308549
• 负责人: KEITH KROLL
• 金额: $ 2.35万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6308549
• 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.

这项研究的目的是研究 估计线粒体质子运动力（PMF）的变化 建模亲脂阳离子的示踪剂动力学， 使用多毛细血管，TC-99M-甲氧基丁丁基甲酸酯（MIBI） 分布式模型。 孤立的工作老鼠心被灌注 在常氧化下含有TL和MIBI的Krebs-Ringer缓冲液（540 Torr） （n = 14）或低氧条件（85 Torr）（n = 6），持续30分钟，然后 切换到无示踪剂灌注液30分钟。 定时冠状窦 （CS），间质液（ISF）和主动脉灌注样品是 收集并确定示踪剂浓度。 ISF和CS示踪剂 使用4个区域，3个屏障血液组织交换拟合曲线 模型，以估计渗透率 - 表面（PS）区域产品 用于毛细管（PSC），肌细胞（PSPC）和线粒体（PSM），以及 心肌（VPC）和线粒体（VM）的分布量 地区。 亲脂阳离子MIBI的VM与 线粒体膜通过Nernst方程和VPC和 肌膜膜电位。 平均 + SD； * = p <0.05 vs tl; ＃ = P <0.05 vs Normogoxic Tracer PSC PSPC PSM VPC VM 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* 低氧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*我们得出了MIBI的估计大PMF（VM）， 相对于TL，与报告的MIBI摄取机制一致 （亲脂阳离子）。 缺氧期间MIBI的VM降低为 与PMF减少一致。