ALTERED METABOLISM IN THE LUNG APPEARS TO BE AN EARLY EVENT IN ACUTE PULMONARY FAILURE SECONDARY TO ENDOTHELIAL CELL DAMAGE, AND MAY BE DETECTED BY AN INCREASE IN THE LEVEL OF FREE 5-HYDROXYTRYPTAMINE (5-HT) IN PULMONARY BLOOD.

ALTERED METABOLISM IN THE LUNG APPEARS TO BE AN EARLY EVENT IN ACUTE PULMONARY FAILURE SECONDARY TO ENDOTHELIAL CELL DAMAGE, AND MAY BE DETECTED BY AN INCREASE IN THE LEVEL OF FREE 5-HYDROXYTRYPTAMINE (5-HT) IN PULMONARY BLOOD. DIRECT AND UNAMBIGUOUS MEASUREMENT OF FREE BLOOD 5-HT LEVELS TO OBTAIN EARYL DIAGNOSIS OF PULMONARY DAMAGE WOULD BE POSSIBLEWITH ELECTROCHEMICAL METHODOLOGY IF AN ELECTRODE OF ADEQUATESPECIFICITY AND SENSITIVITY WERE AVAILABLE. THE GRANTEE WILL INVESTIGATE THE FEASIBILITY OF DEVELOPING A SPECIFIC ELECTROCHEMICAL SENSOR FOR 5-HT CONSISTING OF AN ELECTRODE DERIVATIZED WITH ANTIBODY TO 5-HT. AN ANTIBODY TO 5-HT WILLBE IMMOBILIZED ON ELECTRODE SURFACES BY COVALENT BONDING OR CHEMISORPTION. THE ANTIBODY-DERIVATIZED ELECTRODE, WHEN EXPOSED TO A SOLUTION (E.G., BLOOD, PLASMA) CONTAINING 5-HT,MAY REACT ONLY WITH 5-HT TO PRODUCE AN ELECTROCHEMICALLY MEASURABLE IMMUNE COMPLEX ON THE ELECTRODE SURFACE. AGREEMENT BETWEEN ELECTROCHEMICAL AND FLUOROMETRIC MEASUREMENTS OF 5-HT IN PLASMA AND SERUM WILL CONSTITUTE A DEMONSTRATION OF THE ABILITY OF AN ELECTRODE TO MEASURE 5-HT DIRECTLY IN THE BLOOD. THE SUCCESSFUL COMPLETION OF THE OVERALL PROJECT WILL EVENTUALLY MAKE AVAILABLE FOR THE FIRST TIME TECHNOLOGY FOR PERFORMING RAPID, REAL TIME ANALYSIS OF 5-HT WITHOUT THE NEED FOR SAMPLE MANIPULATION, EXTRACTION, OR RADIOLABELLED REAGENTS. THE AVAILABILITY OF SPECIFIC ELECTRODES FOR 5-HT MAY YIELD DIAGNOSTIC METHODOLOGY FOR THE CLINICAL ASSESSMENT OF PULMONARY ENDOTHELIAL CELL FUNCTION, THROMBOEMBOLIC DISEASE, PLATELET VIABILITY FOLLOWING STORAGE OR INFUSION, AS WELL AS ANY OF THE OTHER PHYSIOLOGICAL OR PATHOLOGICAL STATE IN WHICH 5-HT IS IMPLICATED. THE METHOD OF ANALYSIS IS NOT LIMITED TO 5-HT, BUT CAN BE EXTENDED TO INCLUDE ANY COMPOUND TO WHICH AN ANTIBODY CAN BE PREPARED. THE ELECTRODES TO BE DEVELOPEDCOULD FORM THE BASIS FOR NEW DIAGNOSTIC OR PATIENT MONITORING INSTRUMENTATION FOR USE IN HOSPITALS, CLINCIAL LABORATORIES, PHYSICIANS' OFFICES, OR EVEN AT HOME BY THE PATIENT.