Fetal and newborn cerebral vascular responses and adaptations to hypoxia.

Abstract

I n the developing fetus and newborn infant, as in the adult, regulation of the cerebral circulation is unique in several regards. First, large arteries including the internal carotid, basilar, circle of Wilhs, and immediate branches of these vessels are important resistance vessels. It has been suggested that this arrangement helps to protect cerebral microvessels, and minimizes a vascular “steal” during localized blood flow increases in the brain. Also, cerebral vessels, particularly small arterioles and capillaries, possess a morphological and biochemical barrier between the blood and brain interstitial space. This blood-brain barrier is composed of a continuous endothelium, with tight junctions between adjacent cells. This biochemical barrier consists of high levels of degradative enzymes that prevent circulating neurotransmitters from gaining access to the brain. In addition, this barrier plays a key role in regulating cerebral vascular reactivity, as it does in other vascular beds. In response to physiological stimuli, such as acute hypoxemia, cerebral blood flow increases to maintain a normal rate of oxygen consumption and metabolism. During chronic hypoxia the flow responses exhibit adaptation in direct response to environmental circumstances. To establish some background for an understanding of the role of vascular endothelium in cerebrovascular regulation, we wiI1 first detail several “facts” and the problems associated with them. Fact. Many factors can affect blood flow to the brain and other organs, including changes in 02 and substrate availability, arterial CO, tension, extracellular hydrogen ion concentration, and extrinsic neurovascular influences (see Fig 1). These influences are integrated via homeostatic regulatory mechanisms that maintain brain 02 consumption and metabolism within a given region by altering cerebral vascular resistance. Problem. The question arises how this multitude of factors, both intrinsic and extrinsic to the cerebrovascular system, is orchestrated and integrated to result in precise regulation. Specifically, in regard to the fetus and newborn, to what extent do factors such as immaturity of the receptor populations and their coupling, vascular endothelium, or adrenergic innervation affect the responses? (As an aside, the various models proposed are not simple. Regulation is complicated by interactions and interdependence among many of the variables.) Fact. In the change at birth from fetus to newborn, a large number of cardiovascular, respiratory, hormonal, and metabolic changes occur that can influence cerebral blood flow regulation (see Table 1). Problem. In the face of this virtual physiologic “storm,” the question arises how these changes interact and are orchestrated or integrated to insure optimal function with maintenance of the matching between cerebral blood flow and cerebral metabolic rates. Fact. In response to acute hypoxia, a number of physiologic changes of the cardiovascular, respiratory, and endocrine systems occur. In response to chronic or long-term hypoxia, many different acclimatization responses take place (see Fig 2). Problem. The question arises how the fetus and newborn adjust and/or regulate cerebral blood flow, 02 consumption, etc, to compensate for acute and/or chronic hypoxia, and what role is played by the vascular endothelium in these adaptations. Fact. A number of clinical problems in the fetus and newborn infant occur as sequelae of dysregulation of blood flow to the brain, lungs, and other organs. Problem. A further question regards the means and to what extent the various regulatory factors, including the vascular endothelium, play a roIe in the genesis of these disorders.