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Development of rapid immunoassays for early detection of acute myocardial infarction

Posted on:2001-01-25Degree:Ph.DType:Dissertation
University:Hong Kong University of Science and Technology (Hong Kong)Candidate:Cheng, ShongFull Text:PDF
GTID:1464390014454841Subject:Health Sciences
Abstract/Summary:
The measurement of cardiac marker proteins in plasma of patients with chest pain initially suspected of having an acute myocardial infarction (AMI) is an important parameter for the correct assessment or exclusion of AMI. The aim of the present study is to develop rapid, simple and economical tests for early detection of AMI based on the immunoassay assessment of human heart Fatty Acid-Binding Protein (FABP).;For the FABP detection, a so-called "immunofiltration assay" principle has been developed. It uses a sandwich technique in which capture antibodies were bound to a cellulose membrane and colloidal gold-labeled monoclonal antibodies were used as detectors. The result can be seen after washing as a red spot if FABP is present. Both the qualitative "yes/no" test and the quantitative FABP will hopefully help to make a practical breakthrough in early AMI diagnosis in Hong Kong, China and later Asia, and ultimately the whole world. (Abstract shortened by UMI.).;To develop a sensitive immunoassay, monoclonal antibodies with high affinity for FABP have been developed using hybridoma techniques. Seven monoclonal antibodies were characterized for its specific reaction to FABP including affinity and epitope mapping using surface plasmon resonance. Three separated epitopes have been defined for the seven antibodies. The affinities and epitope map provided important information for the construction of sandwich-type immunoassay for early detection of AMI. The clinical evaluation of 50 chest pain patients presented to Prince of Wales Hospital (Hong Kong) confirmed that FABP elevated in serum as quickly as 1--3 hours after the onset of the first clinical symptoms of AMI. Early detection is important for starting early successful treatment. By monitoring FABP in plasma, the assessment or exclusion of an infarction is possible as early as 1 hour after the admission when the patients are admitted within 24 hours after the onset of the first symptoms of AMI. The alarm system based on displacement immunoassay was established to monitor the increase in FABP on-line. The FABP concentration in serum after reaching a peak value following the onset of AMI, decreases due to elimination of the FABP by the kidneys. This behavior allows not only to calculate the severity of AMI and to backdate the acute event, but also it allows to monitor the reinfarction.
Keywords/Search Tags:AMI, Acute, Early detection, FABP, Immunoassay
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