Each year 750,000 cases of multiple organ dysfunction syndrome (MODS) are diagnosed in critically ill patients in the United States. As a major life threatening complication of trauma and critical illness, MODS is a strong predictor of death. A basic premise for organ failure is an inadequate supply to, extraction by, or utilization of oxygen by the tissues. Under hypoxic conditions, the earliest indicators of compromised oxygenation are found in the gut. Importantly, gut PCO2 reflects inadequate perfusion in relation to cellular metabolic demands. To date, there is no clinically validated threshold prognostic value of gut tissue PCO2 at which dysoxia (critically reduced 02) begins. Identifying a prognostic value would be extremely useful for clinicians for assessing the adequacy of oxygenation. Thus, the purpose of this research is a) to describe the tissues' ability to generate CO2 and buffer metabolic acids at varied points along the Gl tract under aerobic (control) and two anaerobic conditions (respiratory versus metabolic acidosis) and b) to identify the earliest and the most reliable biomarker(s) of dysoxia. This study will examine these metabolic processes in a rat model. The central goal of this research is to identify the threshold values for a site-specific clinically appropriate biomarker of dysoxia with the future potential of using this biomarker to guide therapeutic interventions for individuals at risk for developing MODS. A 3x3x4 experimental design (dysoxic condition x site x time-to-death) will be used to examine regional changes in oxygenation under control and dysoxic conditions at three sites in a rat model (n=91). The independent variables are dysoxic condition (control [no dysoxia], and respiratory and metabolic acidosis), time-to-death (0"""""""", 5"""""""", 15"""""""", 30"""""""", & 40""""""""), and site (rectal, gastric, and sublingual). Data will be collected on PCO2 and 1C pH, the dependent variables, at the three sites. Calculation of bicarbonate will be based on the directly measured variables of tissue PCO2 and 1C pH. Primary statistical tests for evaluating site-specific differences in the generation of CO2 and the buffering of metabolic acids include repeated measures ANOVA, paired comparisons, and multiple regression. Cluster analysis will be used to examine the spatial pattern and temporal evolution of changes in 1C pH in whole tissue at the three sites under all study conditions. Nurses, by their proximity to the bedside, are interdisciplinary team members who play a key role in surveillance to detect early changes in oxygenation. The early identification and treatment of these changes close to the time of insult may prevent or minimize MODS. Findings from this research will support the long- term clinical goal of detecting early changes in tissue oxygenation so that interventions can be developed and systematically tested in clinical populations to prevent and/or limit the progression of MODS.
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| Fisher, Elaine M; Sun, Xiaoyan; Erokwu, Bernadette O et al. (2008) Hypobaric hypoxia reduces GLUT2 transporter content in rat jejunum more than in ileum. Adv Exp Med Biol 614:345-52 |
