Abstract

Many investigators have observed that fetal and neonatal animals are remarkably tolerant to hypoxia compared to the adult. The precise mechanisms however are still unclear. In order to better characterize the hemodynamic and metabolic responses of the fetal brain to hypoxic stress, we have designed a mathematical model to predict tissue oxygenation and metabolic rate of the fetal brain during both moderate hypoxia and severe asphyxia.

The model is based on the Krogh cylinder concept and is similar to one previously published by our lab. Several new concepts were added including the ability to run the model over time using experimental data. Experimentally measured values for cerebral blood flow, arterial oxygen content, and cerebral tissue oxygen PO2 (tPO2) were obtained from chronically instrumented fetuses subjected to 30 minutes of hypoxia or ten minutes of asphyxia. In addition, the capillary spacing of the near term fetal ovine brain in the parietal cortex was measured and found to average 58.2±1.6 μm SD.

In normoxic conditions the model’s prediction of tissue PO2 was close to measured values. However, holding cerebral metabolic rate constant during hypoxia, prediction of tissue PO2 was significantly lower than experimental values, suggesting a decrease in cerebral metabolic rate during hypoxia.

The model was then used to solve for cerebral metabolic rate based on experimentally measured tPO2. The experimentally measured and model predicted cerebral metabolic rates both decreased significantly during hypoxia, indicating the dependence of cerebral metabolic rate on oxygen delivery is stronger than previously thought. These findings may represent a mechanism of adaptive hypometabolism that would serve to ration oxygen use before complete oxygen starvation and help explain the remarkable tolerance of mammalian fetus to hypoxic insults.

LLU Discipline

Physiology

Department

Physiology

School

Graduate School

First Advisor

Gordon G. Power

Second Advisor

John Leonora

Third Advisor

William J. Pearce

Degree Name

Master of Science (MS)

Degree Level

M.S.

Year Degree Awarded

2003

Date (Title Page)

9-2003

Language

English

Library of Congress/MESH Subject Headings

Cerebrovascular Circulation -- physiology; Hypoxia-Ischemia, Brain; Cerebral Anoxia; Fetus; Brain -- metabolism.

Type

Thesis

Page Count

viii; 28

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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