Hu Lufei, Maslanik Tom, Zerebeckyj Mykolai, Plato Craig F
Pharmacological Sciences, Gilead Sciences Inc. Palo Alto, CA, United States.
J Pharmacol Toxicol Methods. 2012 Mar;65(2):75-82. doi: 10.1016/j.vascn.2012.02.001. Epub 2012 Feb 12.
Bioimpedance spectroscopy (BIS) has been used in human and large animal research to assess body fluid compartment volumes (BFC) such as total body water (TBW), extracellular fluid volume (ECFV), and intracellular fluid volume (ICFV). To date, the application of BIS for determination of BFC in small research animals has been limited.
We sought to evaluate the sensitivity and consistency of BIS for the determination of BFC in male SD rats. Thus, in separate series of experiments, we a) compared BFC values determined using BIS to BFC values obtained using radioisotope indicator dilution methods; b) examined day-to-day intra- and inter-rat BFC variability in small (267.8±5.4 g) and large (372.6±5.6 g) rats (n=8/group) as compared to empirical normative mammalian values; c) evaluated the sensitivity of BIS to detect time-dependent responses to repeated administration of a potent diuretic; and d) compared empirically generated BFC data to predicted osmotically-induced ECFV and ICFV shifts in response to i.v. administration of hypotonic (0.3%), isotonic (0.9%) or hypertonic (3.0%) saline (n=6/concentration).
BFC values generated using radioisotope dilution agreed with those generated using BIS. BIS reliably detected differences between small and large rats (p<0.001), and was associated with low (<3.5%) day-to-day, intra-animal coefficient of variation (%=Standard Deviation/mean). BIS detected small reductions (~10%) in ECFV induced by as few as 2 days of the loop diuretic, furosemide, relative to vehicle treatment (70.8±1.5 ml vs. 84.0±1.5 ml; respectively, p<0.05). BIS rapidly detected shifts between ECFV and ICFV in response to osmotic saline challenge, and these responses were similar to physiologically predicted responses.
The current studies support using BIS as a means of sensitively and reliably performing repeated measurements of BFC in rats of a) differing sizes, b) in response to therapeutic agents known to influence renal sodium handling and c) in response to osmotic challenge.
生物电阻抗光谱法（BIS）已用于人类和大型动物研究，以评估体液腔室容积（BFC），如总体水（TBW）、细胞外液容积（ECFV）和细胞内液容积（ICFV）。迄今为止，BIS在小型实验动物中用于测定BFC的应用一直有限。
我们试图评估BIS在雄性SD大鼠中测定BFC的敏感性和一致性。因此，在一系列独立实验中，我们：a）将使用BIS测定的BFC值与使用放射性同位素指示剂稀释法获得的BFC值进行比较；b） 与经验性的正常哺乳动物值相比，检查了小（267.8±5.4 g）、大（372.6±5.6 g）大鼠（每组n = 8）的每日大鼠内和大鼠间BFC变异性；c） 评估BIS检测对强效利尿剂重复给药的时间依赖性反应的敏感性；d） 将经验性生成的BFC数据与静脉注射低渗（0.3%）、等渗（0.9%）或高渗（3.0%）盐水后预测的渗透性诱导的ECFV和ICFV变化进行比较（每种浓度n = 6）。
使用放射性同位素稀释法生成的BFC值与使用BIS生成的值一致。BIS可靠地检测到了大鼠大小之间的差异（p<0.001），并且与每日、动物内变异系数低（<3.5%）（% = 标准差/平均值）相关。与载体处理相比（分别为70.8±1.5 ml和84.0±1.5 ml；p<0.05），BIS检测到仅用2天的袢利尿剂呋塞米诱导的ECFV有小幅度降低（约10%）。BIS快速检测到渗透性盐水刺激后ECFV和ICFV之间的变化，并且这些反应与生理预测反应相似。
当前研究支持将BIS用作一种方法，以灵敏且可靠地对以下大鼠的BFC进行重复测量：a） 不同大小的大鼠，b） 对已知影响肾钠处理的治疗药物有反应的大鼠，以及c） 对渗透性刺激有反应的大鼠。
