A noninvasive method to study regulation of extracellular fluid volume in rats using nuclear magnetic resonance

Abstract

Gordon CJ, Phillips PM, Johnstone AF. A noninvasive method to study regulation of extraceullular fluid volume in rats using nuclear magnetic resonance. Am J Physiol Renal Physiol 310: F426-F431, 2016. First published December 23, 2015 doi:10.1152/ajprenal.00405.2015.-Timedomain nuclear magnetic resonance (TD-NMR)-based measurement of body composition of rodents is an effective method to quickly and repeatedly measure proportions of fat, lean, and fluid without anesthesia. TD-NMR provides a measure of free water in a living animal, termed %fluid, and is a measure of unbound water in the vascular and extracellular spaces. We hypothesized that injecting a bolus of fluid into the peritoneal cavity would lead to an abrupt increase in %fluid and the rate of clearance monitored with TD-NMR would provide a noninvasive assessment of the free water homeostasis in an awake rat. Several strains of laboratory rats were injected intraperitoneally with 10 ml/kg isotonic or hypertonic saline and %fluid was monitored repeatedly with a Bruker "Minispec" TD-NMR body composition system. Following isotonic saline, %fluid increased immediately by 0.5% followed by a recovery over ϳ6 h. Injecting hypertonic (3 times normal saline) resulted in a significantly greater rise in %fluid and longer recovery. Intraperitoneal and subcutaneous fluid injection led to similar rates of clearance. The Wistar-Kyoto rat strain displayed significantly slower recovery to fluid loads compared with LongEvans and Sprague-Dawley strains. Rats exercised chronically showed significant increases in %fluid, but the rate of clearance of fluid was similar to that of sedentary animals. We conclude that this technique could be used to study vascular and extracellular volume homeostasis noninvasively in rats. fluid homeostasis; rodent; noninvasive; unanesthetized; deydration NONINVASIVE MEASUREMENT OF body composition of laboratory rodents is becoming an increasingly popular method to measure body fat as well as other components of body composition without the need for anesthesia or terminating the animal. Magnetic resonance-based systems are used to rapidly measure body composition in awake animals (10, 11). Time-domain nuclear magnetic resonance (TD-NMR) measures the percentages of fat, lean, and fluid of unanesthetized mice and rats (5). The %fluid parameter is a measure of water in a liquid, unbound state and does not include water that is bound in tissue. Hence, %fluid measured by TD-NMR is primarily a measure of unbound fluid in blood and other extracellular fluid compartments. TD-NMR measures of %fluid of rats and mice are typically 7-8% (5).We speculated that the TD-NMR measure of %fluid could be used to study the homeostatic regulation of free water in an awake rodent. That is, if a bolus of saline were to be injected into a mouse or rat, one should be able to measure an abrupt increase in the %fluid. The magnitude of the rise in fluid volume and the rate of clearance of the excess could reflect the capacity of homeostatic processes involved in regulating e...

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“…Body composition was measured using the Bruker LF65 II "Minispec" body composition analyzer (Bruker Optics, Billerica, MA) as previously reported (Gordon et al, 2016). Briefly, a mouse was placed in an acrylic cylinder (48-mm diameter) and was loosely restrained in the cylinder by pushing a plunger to maintain the mouse inside the cylinder based on the size of the mouse.…”

Modeling heart failure risk in diabetes and kidney disease: limitations and potential applications of transverse aortic constriction in high-fat-fed mice

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Sepsis-like Energy Deficit Is Not Sufficient to Induce Early Muscle Fiber Atrophy and Mitochondrial Dysfunction in a Murine Sepsis Model

“…(ii) The increased free fluid mass in the Sepsis mice indicated increased extracellular water and may reflect capillary leakage or kidney failure, as is commonly described in sepsis [ 48 , 49 , 50 , 51 ]. (iii) the lean mass measured by TD-NMR includes the water bound to macromolecules within muscles and their extracellular matrix (composed of ~75% water and ~20% protein) [ 36 , 37 , 52 , 53 ]. As muscle swelling and tissue edema have been well described in human sepsis [ 25 , 54 , 55 ], and since the Sepsis mice had a state of extracellular hyperhydration in our study, such abnormalities may contribute to the overestimation of muscle wet weights, lean mass, and body weight (see Appendix A for more details on TD-NMR analysis, and Supplementary Table S5 , which summarizes the impact of the hydration state in our study).…”

“…Body composition was measured in a non-anesthetized mouse by time-domain nuclear magnetic resonance (TD-NMR) (Minispec fl50 7.5 MHz, Bruker, Billerica, MA, USA). Total body mass was composed of free fluid mass (i.e., unbound water in the vascular and extracellular spaces), fat mass, and lean mass [ 36 ]. The lean mass included dry lean mass and lean-associated water [ 37 ].…”