PILOT & FEASIBILITY STUDIES

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Decreased thyroid function often occurs in critically ill patients and is of prognostic significance. However, it is unknown if hypothyroidism is a cause of organ dysfunction or just an epi-phenomena of acute sepsis. The objective of this study is to determine the ability of exogenous thyroid hormone to improve hepatic bioenergetics in a septic rat model. Bioenergetic function will be assessed by measuring the high energy phosphate levels in the liver using 31P NMR spectroscopy. The experimental animals in the study will be given thyroid treatment immediately following septic induction. The comparison of the high energy phosphate levels between the treatment and non-treatment groups will demonstrate the influence of thyroid function on hepatic bioenergetics Preliminary data show that an injured but unchallenged liver exhibits apparently stable bioenergetic function as assessed by ATP and inorganic phosphate (Pi) concentrations. Subsequently, when the liver is subjected to a metabolic challenge (glucagon), there is an increase in the Pi/ATP ratio. This ratio increase demonstrates the severity to which the liver is dysfunctional from an energetics perspective. Our preliminary data (without the glucagon challenge) have not demonstrated the livers of the septic animals to be bioenergetically unstabIe~therefore, we tested the liver with a glucagon challenge. The preliminary results from these data demonstrate hepatic bioenergetic failure in septic animals, whereas non-septic animals do not. Accordingly, we now propose to study the effects of triiodothyronine (T3) replacement on modifying this hepatic dysfunction. :