MODELING EFFECTS OF PH & MEMBRANE POTENTIALS ON CHARGED SOLUTES

本研究的目的是调查 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-99 m-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 含Tl和MIBI的Krebs-Ringer缓冲液，常氧（540 Torr） （n=14）或缺氧条件（85托）（n=6）持续30分钟，然后 转换为无示踪剂灌注30分钟。 (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跟踪器 使用4个区域、3个屏障的血液-组织交换来拟合曲线 模型，以估计渗透率-表面（PS）面积乘积 毛细血管（PSc）、肌细胞（PSpc）和线粒体（PSm），以及 肌细胞分布容积（Vpc）和线粒体分布容积（Vm） 地区 亲脂性阳离子MIBI的Vm与 线粒体膜电位通过能斯特方程，如Vpc和 肌膜电位。 平均值+标准差; * = p < 0.05 vs T1; # = p < 0.05 vs常氧示踪剂PSc PSpc PSm Vpc Vm常氧Tl 3.45 + 1.05常氧甲基异丁基异腈 0.34+ 0.23* 5.60 + 6.09 1.67 + 1.93 6.05 + 5.19 67.23 + 11.75* 低血糖Tl 2.43 + 1.25 7.00 + 4.60 1.47 + 3.20 3.62 + 2.36 7.39 + 4.52#次氯酸钠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T1，与报道的MIBI摄取机制一致 （亲脂性阳离子）。 缺氧时MIBI的Vm降低， 与PMF的下降一致。

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.