On the pulmonary toxicity of oxygen. 4. The thyroid arena
2011-11,
Shanklin, D. Radford
Normally developed thyroid function is critical to the transition from fetal to neonatal life with the
onset of independent thermoregulation, the most conspicuous of the many ways in which thyroid
secretions act throughout the body. A role for thyroid secretions in growth and maturation of the
lungs as part of the preparation for the onset of breathing has been recognized for some time but how
this contributes to tissue and cell processes and defenses under the duress of respiratory distress has
not been well examined. Extensive archival autopsy material was searched for thyroid and adrenal
weights, first by gestational age, and then for changes during the first hours after birth as ratios to
body weight. After a gestational age of 22 weeks the fetal thyroid and adrenal glands at autopsy in
those with hyaline membrane disease are persistently half the size of those in "normal" infants dying
with other disorders. When the thyroid is examined shortly after birth it reveals a post natal loss of
mass per body weight of similar orders of magnitude which does not occur in the control group. A
clinical sample of premature infants with (12) and without (14) hyaline membrane disease was
tested for T4, TSH, TBG, and total serum protein. The results also demonstrate a special subset with
lower birth weights at the same gestational age, and lower serum T4 and total serum protein. Ventilatory distress in newborn rabbits was induced by bilateral cervical vagotomy at 24 hours post
natal following earlier injection of thyroxine (T4) or thyroid stimulating hormone (TSH) and
comparisons were made with untreated animals and by dose. Early life thyroidectomy was
performed followed by exposure to either air or 100% oxygen. A final experiment in air was
vagotomy after thyroidectomy. Composite analysis of these methods indicates that thyroid factors
are both operative and important in the newborn animal with ventilatory distress. This work and
the archival data indicate those infants destined to develop hyaline membrane disease through
respiratory distress are a distinct developmental and clinical subset with the point of departure from
otherwise normal development and maturation in the second or early third trimester. This interval
is known to be a period of marked variation in the overview indicators of fetal progress through
gestational time. The initiating factor or circumstance which then separates this special subset from
normal future development is placed by these observations firmly into the period when human fetal
TSH dramatically rises 7-fold (17.5-25.5 weeks) followed by a lesser 3 to 4 fold increase in T4
which is extended into the early third trimester. The earlier part of this interval is characterized by
the thyrotrophic action of chorionic gonadotropin (hCG). The possibility that abnormalities in the
intrauterine environment secondary to maternal infection play a role within this time frame is
indicated by the demonstration that interleukin-2 (IL-2) induces an anterior pituitary release of
TSH. Since IL-2 has this property and is not an acute phase cytokine, some form of chronic
infection or an immunopathic process seems more likely as a possible active factor in pathogenesis.
On the pulmonary toxicity of oxygen : III. The induction of oxygen dependency by oxygen use
2010-05,
Shanklin, D. Radford
Oxygen is central to the development of neonatal lung injury. The increase in oxygen exposure of
the neonatal lung during the onset of extrauterine air breathing is an order of magnitude, from a
range of 10-12 to 110-120 Torr. The contributions of oxygen and the volume and pressure
relationships of ventilatory support to lung injury are not easily distinguished in the clinical setting.
Sequential changes in inspired air or 100% oxygen were studied in 536 newborn rabbits without
ventilatory support. Bilateral cervical vagotomies (BCV) were performed at 24 hours post natal to
induce ventilatory distress which eventuates in hyaline membrane disease. The sequences applied
yielded evidence for an induced state of oxygen dependency from oxygen use which was reflected
in differences in survival and the extent of pulmonary injury. The median survival for animals kept
in air throughout was 3 hours. Oxygen before vagotomy or during the first 3 hours afterwards
extended the survival significantly but produced more extensive, more severe, and more rapid lung
lesions. Returning animals to air after prior oxygen exposure reduced the number of survivors past
10 hours and shortened the maximum survival in those groups. These features indicate the
development of a dependency of the defense mechanisms on the availability of oxygen at the higher
level for metabolic and possibly other aspects of the pulmonary and systemic response to injury,
beyond the usual physiological need. Subset analysis revealed additive and latent effects of
oxygen and demonstrated a remarkable rapidity in onset of severe lesions under some
circumstances, illustrating the toxicity of oxygen per se.