This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: In order to study the health implications of plasma hypertonicity, we have developed a new measure of hypertonicity that avoids limitations of currently available indices. This study will allow us to determine if as expected, our new measure varies linearly with the hydration status of normal healthy individuals as they are hydrated and dehydrated, respectively. Goals: Plasma hypertonicity, elevated plasma concentrations of osmotically effective solute (solute that can draw fluid out of cells by osmosis), has been proposed as a marker of the geriatric syndrome known as 'frailty'. Clinical data indicate that plasma hypertonicity causes metabolic and physiologic dysregulation, DNA damage and oxidative stress. Observational data indicate that plasma hypertonicity predicts incident diabetes, disability and mortality, and affects millions of institutionalized and non-institutionalized adults. Interventions to normalize plasma tonicity by diet, activity and/or medications may offer great potential to improve the health of a majority of older adults. Experimental Design: The study participants will be asked to refrain from heavy exercise for 24 hrs before the trial, to eat a prescribed supper at home before 11 pm, but not to consume food or fluid after 11 pm. On arrival at the GCRC at 7 am, each study participant will be given a breakfast consisting of reconstituted frozen orange juice and two toasted English muffins with peanut butter and jelly. After breakfast, urine will be collected and body weight measured. At 7:30 a catheter will be inserted into a forearm vein. The participants will be asked to sit upright for 30 min, after which time a baseline blood sample (20 mL) will be collected. They will be instructed to consume a water load of 20 mL/kg body weight (approximately 1.0-1.5 L) over 45 min, and with the exception of providing urine, remain at rest throughout the study period. Blood and urine samples will be collected and body weight measured 60 min, 6 hrs and 24 hrs following the water load (at 9 am, 2 pm, and 8 am the following morning). In addition to the 20 mL samples of urine collected at specific time points, all urine voided over the 24-hr study period will be collected. At 2 and 7 pm, study participants will be provided standardized meals of dry foods (sandwich, potato chips, cheese pizza and cookies). Food and fluid intake will be restricted after 8 pm. Body weight will be also be measured at 10 pm. Following the last blood sample, urine collection and body weight measurements, study participants will be offered breakfast and adlibitum fluid. They will be discharged with instructions to respond to their thirst by drinking fluids. When data analysis is complete, the study participants will be sent results of their tests and a report of the findings of the study. The individuals who carry out the laboratory tests will be blinded to the hydration status of the study participants. Endpoints: The data we collect from the six individuals in this pilot study will allow us to refine the design we intend to use for the main study. We will use the pilot results to: determine if there are additional covariates or confounders that need to be considered, identify the most appropriate length of fluid restriction and timing for sample collection, calculate the appropriate sample size, refine our hypotheses and statistical methods, as well as provide preliminary indication of the pattern of results that may be expected from a larger study.
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