PORTASYSTEMIC SHUNT QUANTITATION WITH RADIOACTIVE TRACER

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The specific aim of this proposal is to develop and validate a noninvasive, rapid and quantitative method of measuring portasystemic shunting (PSS) in dogs with either spontaneous PSS or induced cirrhosis. The method will involve external monitoring of the kinetics of a radioactive tracer, I-123 labeled iodoamphetamine (IMP), after transrectal administration into the colon. Preliminary studies indicate that this method accurately quantifies PSS in animals with surgically created shunts. The applicability of this method will be evaluated in cirrhotic animals, and validated against the proven standard of microspheres method. This method will be used to determine whether the level of PSS has prognostic value in dogs with spontaneous PSS, and whether administration of beta blockers affects the level of PSS. The goal of this project is to evaluate whether a rational treatment, based on the measurement of PSS, can be developed for patients with portal hypertension. In the United States, most cases of portal hypertension are caused by alcoholic cirrhosis. The complications of portal hypertension are the major causes of mortality and morbidity in alcoholics. While a number of therapies have been successful in treating selected groups of patients, definitive benefits in all patients have not been demonstrated. This may be due to the lack of an objective indicator of favorable response to the different therapies. The basic abnormality in cirrhosis is mechanical obstruction of portal blood flow, resulting in portal hypertension and PSS. A hepatic encephalopathy and probably survival. In all patients treated with beta blockers for variceal bleeding, PSS is decreased to various degrees while other portal hemodynamic parameters respond unpredictably. Therefore, the degree of PSS response to beta blocker may be an important indicator of whether the patients are likely to benefit from this form of therapy. The level of PSS reflects the total amount of variceal blook flow and is probably related to both the variceal size and the likelihood of variceal bleeding. The level of PSS may therefore be an important prognostic indicator. For these reasons, PSS is potentially important in patient management. The development of an accurate, noninvasive and reproducible method for its measurement under different conditions is warranted.