MODELING EFFECTS OF PH & MEMBRANE POTENTIALS ON CHARGED SOLUTES

这项研究的目的是调查 线粒体质子推动力(PMF)的变化 对亲脂性阳离子的示踪动力学进行建模， TC-99M-甲氧基异丁基异腈(MIBI)，使用多毛细管 分布式模型。分离的工作大鼠心脏灌流 常氧(540Torr)下含TL和MIBI的Krebs-Ringer缓冲液 (n=14)或低氧条件(85托)(n=6)30分钟，然后 改用不含示踪剂的灌流液30分钟。定时冠状静脉窦 (CS)、间质液(ISF)和主动脉灌流液样本 收集并测定示踪剂浓度。ISF和CS示踪剂 使用4个区域、3个屏障的血液-组织交换来拟合曲线 模型，以估算渗透率-表面积乘积 对于毛细血管(PSC)、心肌细胞(PSPC)和线粒体(PSM)，以及 心肌细胞(VPC)和线粒体(Vm)的分布体积 地区。亲脂性阳离子MIBI的Vm与 线粒体膜电位与VPC和Nernst方程的关系 肌膜电位。平均值+SD；*=p&lt；0.05与TL；# =p&lt；0.05与常氧Tracer 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* 缺氧性TL 2.43+1.25 7.00+4.60 1.47+3.20 3.62+2.36 7.39+ 4.52#缺氧性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，与已报道的MIBI摄取机制一致 (亲脂性阳离子)。低氧时MIBI的Vm降低为 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.