Developmental changes in cerebral autoregulatory capacity in the fetal sheep parietal cortex

Abstract

We validated laser Doppler flowmetry (LDF) for long-term monitoring and detection of acute changes of local cerebral blood flow (lCBF) in chronically instrumented fetal sheep. Using LDF, we estimated developmental changes of cerebral autoregulation. Single fibre laser probes (0.4 mm in diameter) were implanted in and surface probes were placed on the parietal cerebral cortex at 105 ± 2 (n = 7) and 120 ± 2 days gestational age (dGA, n = 7). Basal lCBF was monitored over 5 days followed by a hypercapnic challenge (fetal arterial partial pressure of CO 2 , P a,CO 2 : 83 ± 3 mmHg) during which lCBF changes obtained by LDF were compared to those obtained with coloured microspheres (CMSs). Mean arterial blood pressure (MABP) was increased and decreased using phenylephrine and sodium nitroprusside at 110 ± 2 and 128 ± 2 dGA. Intracortical and cortical surface laser probes gave stable measurements over 5 days. The lCBF increase during hypercapnia obtained by LDF correlated well with flows obtained using CMS (r = 0.89, P < 0.01). The signals of intracortical and surface laser probes also correlated well (r = 0.91, P < 0.01). Gliosis of 0.35 ± 0.06 mm around the tip of intracortical probes did not affect the measurements. The range of MABP over which cerebral autoregulation was observed increased from 20-48 mmHg at 110 dGA to 35 to > 95 mmHg at 128 dGA (P < 0.05). Since MABP increased from 33 to 54 mmHg over this period (P < 0.01), the range between the lower limit of cerebral autoregulation and the MABP increased from 13 mmHg at 110 dGA to 19 mmHg at 128 dGA (P < 0.01). LDF is a reliable tool to assess dynamic changes in cerebral perfusion continuously in fetal sheep.

Cerebral O2 Supply Thresholds for the Preservation of Electrocortical Brain Activity During Hypotension in Near-Term-Born Lambs

“…A number of studies reported autoregulation of the CBF in a lamb model. The MABP values that corresponded to the lower limit of the autoregulatory plateau in these studies were reported to range between 30 and 45 mm Hg for preterm and near-term fetal lambs (31)(32)(33)(34)(35), which is in accordance with the threshold value of MABP for maintenance of CBF that we observed in the 141-d born lambs. Although those studies were conducted earlier in gestation, they were performed in animals in an intrauterine situation and not exposed to birth stress.…”

Pulmonary Distribution of Lucinactant and Poractant Alfa and Their Peridosing Hemodynamic Effects in a Preterm Lamb Model of Respiratory Distress Syndrome

“…6). Although the current experiments are the first to demonstrate CBF autoregulation in an ex utero preterm lamb, the findings are also in accordance with studies of fetal sheep in utero as early as 110 d gestation (9). However, it is possible that CBF autoregulation is impaired in the infant relative to the preterm lamb and thus caution is warranted in extrapolating lamb studies to the infant.…”

“…LDF methodology provides a continuous measurement of changes in brain blood flow that correlate well with flow measurements using microsphere (5,9). LDF is capable of measuring rapid changes in CBF associated with acute hypoxia (5) or umbilical cord occlusion (10), so the likelihood that significant changes in CBF-escaped detection in the current experiments are small.…”

Cerebral Blood Flow Heterogeneity in Preterm Sheep: Lack of Physiologic Support for Vascular Boundary Zones in Fetal Cerebral White Matter

“…Immature fetal sheep do not appear to autoregulate flow in the cortex, white matter, thalamus, or brainstem (Muller et al, 2002;Szymonowicz et al, 1990), and data are also controversial in human (Menke et al, 1997;Soul et al, 2007;Tsuji et al, 2000;Tyszczuk et al, 1998). Although our experiments did not directly address this hypothesis, our current data do not support that explanation.…”