The precise role of CO 2 in cerebral oxygenation is not as well defined as O 2 , especially in the immature brain. In the ovine fetus, we tested the hypotheses that arterial PCO 2 (PaCO 2 ) plays a critical role not only in the regulation of cerebral blood flow but also in the regulation of cerebral tissue oxygenation. I n the developing fetus and newborn infant, as well as the adult, the maintenance of optimal cerebral oxygenation is of critical importance, as the brain is highly dependent on a continuous and adequate O 2 supply to maintain structural and functional integrity. Cerebral tissue oxygenation is maintained and carefully regulated by the balance of several factors. These include CBF, arterial O 2 partial pressure (PaO 2 ) and content, cerebral metabolic rate for O 2 (CMRO 2 ), and the relative position of the Hb-oxygen dissociation curve (1,2). Arterial CO 2 tension (PaCO 2 ) long has been recognized as playing a major role in CBF regulation of the fetus (3) as well as the adult (4,5). Thus, it is reasonable to anticipate that CO 2 , as well as O 2 , plays a significant role in cerebral tissue oxygenation.Variation of PaCO 2 commonly occurs in the management of the fetus and newborn during the perinatal period. During labor, fetal hypercapnia with respiratory acidosis, in part resulting from transient compression of the umbilical cord, is not uncommonly seen (6). In addition, vaginal delivery itself may be associated with respiratory acidosis and hypoxia (7). Alternatively, with moderate to severe maternal hyperventilation, particularly during the later stages of labor, fetal hypocapnia with respiratory alkalosis may develop (8,9). In addition, among critically ill newborn infants, significant changes in PaCO 2 can present problems. Under some circumstances, hypocapnia is believed to be of value to prevent an excessive increase in CBF. In other instances, "permissive" hypercapnia is practiced to optimize CBF, to reduce the risk of periventricular leukomalacia, and to minimize ventilator-associated lung injury (10). Nonetheless, despite the critical importance of these issues, and knowledge that cerebrovascular PaCO 2 reactivity differs dramatically between the immature and mature organism (11), the role of CO 2 in cerebral tissue oxygenation has received relatively little attention, especially in the immature brain. (12)(13)(14).
MATERIALS AND METHODSExperimental animals and instrumentation. For these studies, we used six pregnant Western ewes and their singleton fetuses obtained from Nebeker Ranch (Lancaster, CA). All surgical and experimental procedures were performed within the regulations of the Animal Welfare Act, the National Institutes of Health Guide for the Care and Use of Laboratory Animals, "The Guiding Principles in the Care and Use of Animals" approved by the Council of the American Physiologic Society, and the Animal Care and Use Committee of Loma Linda University.Pregnant ewes and their fetuses were instrumented at 122 Ϯ 3 d of gestation (term 145 d), as we have described in...