Abstract

Previous studies dealing with the effects of oral acetazoleamide (DiamoxR) administration in humans have yielded equivocal results. Effects of intravenous administration of this agent, a potent carbonic anhydrase inhibitor, have not been studied until recently. It is postulated that difficulty in interpreting these results has risen in part from failure to evaluate given parameters in terms of drug concentrations or degree of carbonic anhydrase inhibition achieved.

These concentrations were ascertained throughout the present work of this Thesis, which deals with the effects of both small and large doses of this agent upon ventilatory parameters in man.

In these studies, normal fasting young males were first studied after an oral dose of 10 mg/kg using standard techniques of spirometry and gas analysis. No differences in minute volume, end-tidal (alveolar) pCO>2/ or other ventilatory parameters were observed one hour after the drug was administered, while breathing room air or 10% oxygen at rest. However, an increased ventilatory response to 2 and 4% carbon dioxide in air was observed after oral administration of this dose.

After a sufficiently large (35-50 mg/kg) intravenous dose, a concentration-related decrease in the alveolararterial (A/a) pC02 ratio similar to that earlier observed in dogs was observed. Blood gas determinations were carried out using suitable electrodes. The A/a pCO2 ratios after this dosage were between 0.8-0.6 at rest (normal*!.0) and dropped to 0.3 during exercise. This decrease was effected at a red cell concentration of from 60-80 micrograms/ ml, considerably greater than that necessary to achieve similar results in dogs. This decrease in A/a pCO2 ratio was associated with a transient hyperpnea and a fall in respiratory quotient secondary to a decrease in carbon dioxide output.

These data are interpreted as indicating a definite. dose-related effect of acetazoleamide upon carbon dioxide output and ventilation in humans. The acute effects of the drug occur prior to the renal diuresis of bicarbonate, and are consistent with the development of an impediment to carbon dioxide transport across the alveolar-capillary junction in the lung. These effects are maximal when the transport time of the blood through the lung is shortened and the metabolic production of carbon dioxide is increased, as is the case during exercise. In this case, the speed of the alternate carriage mechanisms (primarily carbaminobound carbon dioxide) are probably not adequate to handle the increased demands placed upon the carriage system.

These studies indicate that at dosage levels which can be tolerated by humans the drug probably has no use in producing a rapid, artificial acclimatization to high altitude.

Recent in vitro studies have indicated quantitative differences between canine and human erythrocytic carbonic anhydrase. These differences probably account for the discrepancies which have existed in data obtained from such subjects.

LLU Discipline

Physiology

Department

Physiology

School

Graduate Studies

First Advisor

J. Earl Thomas

Second Advisor

Clarence R. Collier

Third Advisor

U. D. Register

Fourth Advisor

Jack D. Zwemer

Fifth Advisor

Robert B. Pearson

Sixth Advisor

Guy M. Hunt

Degree Name

Master of Science (MS)

Degree Level

M.S.

Year Degree Awarded

1960

Date (Title Page)

6-1960

Language

English

Library of Congress/MESH Subject Headings

Acetazolamide; Carbon Dioxide

Type

Thesis

Page Count

xi; 98

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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