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Placental (К^Сgeké S PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/147916 Please be advised that this information was generated on 2021-09-24 and may be subject to change. PLACENTAL (К^СGEKÉ S * Уп^ггі«» ¿л i ι) Дстг R.H.W. LORIJN ^ FETAL OXYGEN CONSUMPTION AND PLACENTAL OXYGEN EXCHANGE PROMOTORES PROF. DR LD. LONGO PROF. DR Т.К.A.B. ESKES CO-REFERENT DR L.L.H. PEETERS FETAL OXYGEN CONSUMPTION AND PLACENTAL OXYGEN EXCHANGE PROEFSCHRIFT ter verkrijging van de graad van doctor in de geneeskunde aan de Katholieke Universiteit te Nijmegen, op gezag van de Rector Magnificus Prof. Dr. P.G.A.B. Wijdeveld, volgens besluit van het College van Decanen in het openbaar ter verdediging op vrijdag 9 mei 1980 des namiddags te 2.00 uur precies door RONALD HANS WILMAR LORIJN geboren te 's Gravenhage Krips Repro Meppel 1980 This study was performed during a two year research fellowship in the Department of Perinatal Biology, Loma Linda University, School of Medicine, Loma Linda, California 92350, U.S.A., under the guidance of Prof. Dr. L. D. Longo. A Nato Grant awarded by the Netherlands Organization for the Advancement of Pure Research (Z. W. O. ) and U. S. P. H. S. Grant 03807 furnished the financial support of the investigation. "Therefore, one concludes that one and the same soul governs the bodies and one and the same nourishes both. " Leonardo da Vinci Copyright 1980. All rights reserved. No part of this publication may be reproduced in any form by any photomechanical means without permission from the author. To Hansje To Rosa Maria, Vivienne, Geraldine To my parents Aknowledgements The completion of this thesis gives me an excellent opportunity to express my sincere feelings of indebtedness to all who have contributed to it's realization My parents, who not only gave me a youth free from care, but also stimulated me to accept challenges in order to explore the unknown. The staff members, technicians and research fellows of the Dept. of Perinatal Biology of Loma Linda University, who created an unforgettable and inspiring atmosphere of friendship and dedication to research. Mrs. Helen Little and Mrs. Linda Moore for editorial assistance, while back in Holland Miss Ciska Don helped me to put the finishing touches to the work. Rosa Maria, a ti en particular debo mucho agradecimiento, por que todo esto ha sido posible por tu apoyo permanente. CO NTENTS page I. INTRODUCTION 15 II. FETAL OXYGEN CONSUMPTION AND PLACENTAL EXCHANGE 18 UNDER PHYSIOLOGICAL CONDITIONS 1. Maternal Blood Oxygen Affinity and Capacity 18 1.1. General Considerations 18 1.2. Hemoglobin 18 1.3. Blood Oxygen Affinity and the Oxyhemoglobin saturation 20 curve 1.4. Blood Oxygen Capacity 23 2. Fetal Blood Oxygen Affinity and Capacity 25 2.1. Fetal Hemoglobin 25 2.2. Blood Oxygen Affinity 29 2. 3. Blood Oxygen Capacity 32 3. Interrelations of Maternal and Fetal Blood Oxygen Affinity and Capacity 33 3.1. General Considerations 33 3. 2. Species Differences 38 4. Relation of Maternal and Fetal Oxygen Partial Pressures to Placental Oxygen Exchange 38 4.1. Theoretical Considerations 38 4.2. Experimental Studies 43 4.3. Clinical Implications 49 4.3.1. Maternal Oxygen Inhalation 49 4. 3. 2. Hyperbaric Oxygenation 51 4.3.3. Acute Decrease in Inspired Oxygen Tension 52 4.3.4. Chronic Decrease in Maternal Inspired Oxygen - High Altitude 54 4.3.5. Chronic Maternal Hypoxemia - Cyanotic Congeni­ tal Heart Disease 58 5. Relation of Maternal and Fetal Oxygen Affinity to Placental Oxygen Exchange 60 5.1. Theoretical Considerations ¿0 11 page 5.2. Decreasing Fetal Blood Oxygen Affinity by Intrauterine Transfusion 63 5. 3. Changes in Oxygen Affinity due to Hemoglobinopathies ^6 5.4. Maternal Hyperventilation and Other Conditions 71 6. Relation of Maternal and Fetal Placental Hemoglobin Flow to Placental Oxygen Exchange 74 6.1. General Considerations 74 6.2. Theoretical Considerations 77 6. 3. Experimental Studies 80 6.4. Clinical Implications 85 7. Interrelations of Maternal and Fetal Placental Flows and Oxygen Exchange 89 7. 1. Distribution of Maternal and Fetal Placental Flows 89 7.1.1. Nonuniform Distribution of Maternal and Fetal Blood Flows 89 7. 1. 2. Distribution of Placental Diffusing Capacity to Blood Flows 9' 7.2. "Sluice" or "Waterfall" Flow in the Placental Vessels 91 7.3. Uterine Contractions and Oxygen Exchange 94 III. TRANSFER OF OXYGEN DURING INCREASED FETAL OXYGEN CONSUMPTION 97 1. Introduction 97 2. Methods and Materials 98 2.1. Surgical Procedure 98 2.2. Experimental Procedure 100 2.2.1. Norepinephrine 100 2.2.2. 3,5,3'-L-Triiodothyronine 101 2.3. Blood Flows and Cardiac Output 101 2.4. Placental Carbon Monoxide Diffusing Capacity 104 2.5. Hormones Determination 106 2.6. Statistical Analysis 107 3. Results 107 3.1. Norepinephrine 107 3.1.1. Plasma Catecholamine concentrations 107 12 page 3.1.2. Fetal Oxygen Consumption 112 3.1.3. Placental Diffusing Capacity 112 3.1.4. Cardiovascular Responses 114 3.1.4.1. Maternal Ш 3.1.4.2. Fetal lU 3.1.4.3. Norepinephrine Dose-Response Relations 114 3.1.4.4. Cardiac Output and Blood Flow 3.2. 3,5,3'-L-Triiodothyronine Changes 117 3.2.1. Changes in Thyroid Hormones 119 3.2.2. Fetal Plasma Cortisol and Catecholamine Concentrations 119 3.2.3. Fetal Oxygen Consumption 119 3.2.4. Placental Carbon Monoxide Diffusing Capacity 121 3.2.5. Cardiovascular Responses 121 3.2.5.1. Maternal 121 3.2.5.2. Fetal 121 3.2.5.3. Blood Flow and Cardiac Output 121 3.2.5.4. Histological Examination of the Fetal Lung 124 DISCUSSION 125 1. Fetal Oxygen Consumption '25 1.1. Previous Estimates of Fetal Oxygen Consumption 125 1.2. Physiological Implications ^5 1.3. Clinical Implications 130 2. Norepinephrine Experiments 13' 2.1. Catecholamine Concentrations in the Mother and Fetus 131 2. 2. Cardiovascular Responses and Results of Previous Studies in the Fetus and Newborn 132 3. 3, 5, 3' - L - Triiodothyronine Experiments 134 3. 1. General Considerations ^35 3. 2. Thyroid Development and Effects upon the Fetus 136 3. 3. Changes in Maternal and Fetal Hormone Concen­ trations 136 page 3.4. Fetal Cardiovascular Responses 139 4. Comparison of Norepinephrine and 3,5,3' - L - Triiodothyro­ nine Results 139 V. SUMMARY 141 VI. BIBLIOGRAPHY 144 CURRICULUM VITAE 14 I. Introduction The developing fetus presents α paradox of sorts. On one hand, its arterial blood oxygen tension is only 20 to 30 torr as compared with adult values of about 100 torr. In addition, its rate of oxygen consumption is twice that of the adult per unit weight (8 vs 4 mUmin . kg ), and its oxygen reserve (that amount of oxygen contained in its blood and tissues) is only enough to meet its metabolic needs for one to two minutes. On the other hand, fetal blood oxygen affinity in humans and most other species exceeds that of the adult, and its blood O« capacity (a function of the hemoglobin concentration) is greater than that of the adult, at least during the later part of pregnancy. A complicating factor is that the flow of maternal and fetal blood to the placental exchange area must be reasonably matched for optimal oxygen transfer and transport to the fetal tissues. The question naturally arises how these and other factors interact to fit the fetus for its unique existence and optimal development. An additional question concerns the factors which limit placental oxygen transfer and the fetus' ability to withstand alterations in this exchange process. Because the integrity of neural and other vital cells require a relatively unin­ terrupted oxygen supply, the processes whereby oxygen cascades by convection and diffusion from the mother's ambient environment to the cristae of the fetal mitochondria must be exquisitely regulated at each step. A critical link in this chain of sequential events is the placenta where a volume of oxygen sufficient to supply fetal needs must diffuse across the membranes from maternal to fetal blood during the short time the two circulations are in close contact. This process is a function of maternal and fetal arterial O- partial pressures, maternal and fetal hemoglobin O« affinities, maternal and fetal placental hemoglobin flow rates, the diffusing capacity of the placenta, the vascular relations of maternal to fetal vessels, the amount of CO- exchanged, and several other factors (Longo et al., 1972). 15 Eoch of these Factors in turn consists of numerous component elements. Tight coupling between the oxygen transport characteristics of both maternal and fetal blood and the respective blood flows is required. This subject is of importance in understanding the physiologic factors which affect placental oxygen exchange, their interactions, dynamics, and specific control mechanisms. In addition, the topic is of clinical importance in understanding the basis of normal and abnormal placental exchange and fetal oxygenation during pregnancy, labor, and delivery. Therefore the first part of the thesis attempts to synthesize into a coherent whole many of the isolated and seemingly inconsequential findings reported during the past decade or so. It seeks to derive an understanding of the role of maternal and fetal blood oxygen tensions, blood O- affinities and capacities, and blood flows in affecting transplacental oxygen exchange, and thus oxygenation of the fetus. Specific questions which we will address include the following: 1) How is the physiologic function of maternal hemoglobin correlated with its chemical structure? 2) What changes
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