- 作者：Lufei Hu ; lufei.hu@gilead.com ; Tom Maslanik ; Mykolai Zerebeckyj ; Craig F. Plato
- 关键词：BIS ; bioimpedance spectroscopy ; BFC ; body fluid compartment volumes ; TBW ; total body water ; ECFV ; extracellular fluid volume ; ICFV ; intracellular fluid volume ; VAP ; vascular access port
- 刊名：Journal of Pharmacological and Toxicological Methods
- 出版年：2012
- 期刊代码：28_10568719
- 类别：pha
- 出版时间：March-April, 2012
- 卷：65
- 期：2
- 页码：75-82
- 文件大小：605 K
Introduction
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.Methods
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 卤 5.4 g) and large (372.6 卤 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).
Results
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 卤 1.5 ml vs. 84.0 卤 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.
Discussion
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.