Date of Award

1-2-1990

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Physiology and Pharmacology

Abstract

Histamine, a biogenic amine which may be released as a result of allergic reaction, is known to cause coronary artery spasm in vivo and in vitro. This study addressed the question of whether or not there is a relationship between allergy and coronary artery spasm. Objectives of the study were to compare quantities of immunologically-mediated histamine release from tissues obtained from patients with varying degrees of allergy and coronary artery disease, and to compare changes in coronary artery contraction induced by immunological challenge.After obtaining approvals for human subjects research, coronary artery samples were obtained at autopsy from 25 patients at a major medical center. Ring segments of tissue were suspended in an isolated muscle bath apparatus and equilibrated in buffer at 37 degrees centigrade. Continuous mechanograms were recorded via a force-displacement transducer. Tissues were tested for viability with addition of a hypertonic potassium chloride solution. After washout and re-equilibration, tissues were incubated with anti-IgE, an agent which simulated an antigen in this preparation.Tested tissues and untested tissues from the same subjects were analyzed for histamine content using a conjugation-based assay and fluorescence spectrophotometry. Histamine release into the muscle bath was assayed by the same method. Patient medical records were screened for pertinent history of allergy and/or coronary artery disease. Pathological evidence of coronary artery disease was obtained from autopsy reports.While statistical significance was not achieved in most cases, clear differences of potential clinical significance were apparent upon analysis of the results. Tissues from patients with both allergy history and mild-to-moderate degrees of coronary atherosclerosis generated greater force in response to anti-IgE challenge. The results for histamine content of unchallenged tissues and for residual histamine content in tested tissues were contradictory, possibly because of lack of sensitivity of the histamine assay.Refinements of methodology which resulted from this study include a rudimentary classification system for vascular smooth muscle waveforms and several correlational analyses of potential intervening variables in isolated vessel research.

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