Developmental Changes in Thickness, Contractility, and Hypoxic Sensitivity of Newborn Lamb Cerebral Arteries

Abstract

[S.A.j ischemia, edema, and infarction. Concomitant elevations in arterial carbon dioxide tension and compensatory increases in blood pressure may acutely increase cerebral blood flow, but these changes can also contribute to the development of subependymal or intraventricular hemorrhage ( I, 2), particularly upon reoxygenation. Such pathophysiological changes demonstrate that regulation of cerebral perfusion in the newborn is impaired by hypoxia (3). The reasons for this impairment, however, remain unclear.The vulnerability of the newborn cerebral circulation to hypoxic damage may be due to age-related differences in vascular structure and function. In newborn vessels, wall thickness and tension-generating capacity are decreased relative to corresponding adult vessels (4). Adrenergic innervation and recepto r sensitivity are also decreased (5, 6). These differences are of importance not only at the microcirculatory level, but also in the large cerebral arteries which, in the adult , can contribute up to 50% of total cerebrovascular resistance (7). Thus, newborn vessels may not be able to adjust with the speed and force required to maintain cerebral perfusion during hypoxia, or to limit cerebral perfusion during reoxygenation. To explore this hypothesis, we examined the rates and magnitudes of relaxation during hypoxia in carotid and cerebral arteries isolated from newborn lambs and adult sheep. Vessel thicknesses and normoxic force developm ent were also examined and compared. We paid particular attention to the differences between carotid and cerebral arteries, and to the effects of maturation on these differences. METHODSSegments of rostral choroidal, posterior communicating, basilar, and common carotid arteries were obtained from 3-to 7-day-old lambs and adult sheep and studied using standard in vitro techniques (5, 8). Each segment was cut to a length of 5 mm , cannulated with mou nting wires, and suspended between a Grass IT.03 force transducer and a post attached to a microm eter used to control resting tension. The segments were equilibrated in a bicarbonate Krebs solution containing (in mM/liter): NaCI 122, NaHC03 25.6, dextrose 5.56, KCl5.17, MgS0 4 2.49, CaCh 1.60, ascorbic acid 0.114, and disodium EDTA 0.027. During equilibration, the vessel segments were stretched to obtain optimal resting tensions of 0.5 to 1.0 g for the cerebral and carotid artery segments. Optimal values of resting tension were determined in preliminary length-tension studies. Unl ess otherwise specified, the vessels were continuously bubbled with 95% Os, 5% CO2 and maintained at normal body temperature.Each vessel segment was contracted three times in succession by exposure to an isotonic Krebs solution containing 120 mM KCl and 5.2 mM NaC!. Each contraction lasted 24 min , with a 30-min rest period in normal Krebs allowed between consecuti ve 192ABSTRACf. The present studies were conducted to examine the possibility that the increased vulnerability of the newborn brain to hypoxia may be due to age-related differences in vas...

Regional Variation of Postjunctional α- Adrenoceptor Responses in the Developing Renal Vascular Bed of Sheep

“…Pearce and Ashwal (29) found results similar to ours in the carotid artery using KC1 depolarization and attributed the decrease in maximum tension developed to the thicker arterial wall found in the mature animal. The thicker wall is thought to be due to more increases in collagen and elastin than contractile proteins (1 8,30).…”

Maturational Modification of Hypoxic Relaxation in Ovine Carotid and Cerebral Arteries: Role of Endothelium

“…In turn, the extent and character of cerebrovascular reactions to hypoxia in large part determine the ability of the cerebrum to endure any hypoxic insult. Previous studies of hypoxic cerebral vasodilation suggest that the sensitivity of cerebral arteries to the direct effects of hypoxia changes significantly during the perinatal period [7][8][9]. Other studies further suggest that endothelial capacity to modulate vascular tone also changes with age [10,11].…”

“…Other studies further suggest that endothelial capacity to modulate vascular tone also changes with age [10,11]. Superimposed on these variations is the general tendency of the effects of hypoxia on cerebral arteries to vary with artery size, and as for responses to hypercapnia, to be of greater magnitude in the smaller, more muscular arteries than in the larger more elastic arteries of the cerebral circulation [7][8][9]. In light of these findings, we hypothesize that the relative contribution of the endothelium to hypoxic cerebrovascular vasodilation changes with age and artery type.…”

Cerebral blood flow during hypoxic hypoxia with plasma-based hemoglobin at reduced hematocrit

“…Because isolated cerebral arteries can relax at low PO 2 (31,32), intravascular PO 2 sensors may also be involved. Comparison of the albumin and hemoglobin groups at equivalent hematocrit implies a greater role for tissue PO 2 than vascular PO 2 .…”