scholarly journals Effects of betamethasone administration to the fetal sheep in late gestation on fetal cerebral blood flow

2000 ◽  
Vol 528 (3) ◽  
pp. 619-632 ◽  
Author(s):  
Matthias Schwab ◽  
Marcus Roedel ◽  
M. Akhtar Anwar ◽  
Thomas Müller ◽  
Harald Schubert ◽  
...  
1991 ◽  
Vol 11 (3) ◽  
pp. 416-423 ◽  
Author(s):  
Conrad R. Chao ◽  
A. Roger Hohimer ◽  
John M. Bissonnette

The early time period following ischemia may be of pathogenetic importance in hypoxic-ischemic brain injury. Global cerebral oligemia was induced in ten late gestation fetal sheep by inflation of a balloon occluder around the brachiocephalic artery. Cerebral blood flow, oxygen, glucose, and lactate net flux, and oxygen delivery were measured by the Fick principle following 1 h of oligemia and at 5, 30, and 60 min of postoligemic reperfusion. During oligemia, cerebral blood flow decreased by 74 ± 10% (mean ± SD) and oxygen consumption decreased by 34 ± 24%. The glucose:oxygen quotient was elevated throughout the oligemic period. In the early (5 min) reperfusion period, blood flow and oxygen delivery were not different from control but oxygen consumption was persistently depressed by 27 ± 32%; fractional extraction of oxygen was 0.38 ± 0.10 during control and 0.24 ± 0.09 during early reperfusion. The venous oxygen tension increased modestly from 15.2 ± 2.4 to 18.0 ± 1.7 mm Hg; the postoligemic venous pO2 was limited by the lack of reactive hyperemia combined with the low arterial pO2 of the intrauterine environment. Postoligemic carbohydrate fluxes could not be differentiated from control, possibly due to blood–brain barrier limitations. These factors may be related to the relative resistance of the fetal brain to hypoxic–ischemic injury.


1999 ◽  
Vol 277 (5) ◽  
pp. R1268-R1273 ◽  
Author(s):  
Haiyan Tong ◽  
Charles E. Wood

Previous studies by us and others have demonstrated that PGE2 and thromboxane (Tx) B2 are produced in the fetal and neonatal brain during cerebral hypoperfusion. The present study was to test the hypotheses that indomethacin would alter the cerebral blood flow (CBF) response to reduced cerebral perfusion pressure in late-gestation fetal sheep by inhibiting the local prostanoid production. We studied eight chronically catheterized, sinoaortically denervated, 126- to 136-day gestation fetal sheep. The cyclooxygenase inhibitor indomethacin (0.2 mg/kg) or its vehicle phosphate buffer was injected intravenously 90 min before the start of a 10-min period of cerebral hypoperfusion produced by brachiocephalic artery occlusion (BCO). We found that BCO decreased fetal regional CBF (rCBF) by 65–79% in the phosphate buffer group and by 45–57% in the indomethacin-pretreated group. The decrease in fetal rCBF during BCO after indomethacin was 30–49% less than after phosphate buffer. Plasma PGE2 and TxB2 concentrations were significantly reduced by indomethacin treatment. BCO increased plasma ACTH and arginine vasopressin (AVP) concentrations; but these responses were not affected by indomethacin. These data suggested that endogenous prostanoid production is involved in the regulation of fetal CBF but, in the absence of intact baro- or chemoreflexes, not in the regulation of ACTH or AVP responses to BCO. We conclude that indomethacin has a beneficial effect on CBF during cerebral ischemia in late-gestation fetal sheep.


2007 ◽  
Vol 28 (5) ◽  
pp. 995-1008 ◽  
Author(s):  
Melissa M McClure ◽  
Art Riddle ◽  
Mario Manese ◽  
Ning Ling Luo ◽  
Dawn A Rorvik ◽  
...  

Periventricular white matter (PVWM) injury is the leading cause of neurologic disability in survivors of prematurity. To address the role of ischemia in PVWM and cerebral cortical injury, we hypothesized that immaturity of spatially distal vascular ‘end zones’ or ‘border zones’ predisposes PVWM to greater decreases in cerebral blood flow (CBF) than more proximal structures. We quantified regional CBF with fluorescently labeled microspheres in 0.65 gestation fetal sheep in histopathologically defined three-dimensional regions by post hoc digital dissection and coregistration algorithms. Basal flow in PVWM was significantly lower than in gyral white matter and cortex, but was equivalent in superficial, middle, and deep PVWM. Absolute and relative CBF (expressed as percentage of basal) did not differ significantly during ischemia or reperfusion between PVWM, gyral white matter, or cortex. Moreover, CBF during ischemia-reperfusion was equivalent in three adjacent PVWM levels and was not consistent with the magnitude of severity of PVWM injury, defined by TUNEL (terminal deoxynucleotidyltransferase-mediated dUPT nick end labeling) staining. However, the magnitude of ischemia was predicted by the severity of discrete cortical lesions. Hence, unlike cerebral cortex, unique CBF disturbances did not account for the distribution of PVWM injury. Previously defined cellular maturational factors, thus, appear to have a greater influence on PVWM vulnerability to ischemic injury than the presence of immature vascular boundary zones.


2011 ◽  
Vol 110 (5) ◽  
pp. 1362-1373 ◽  
Author(s):  
Joseph J. Smolich ◽  
Jonathan P. Mynard ◽  
Daniel J. Penny

Although the distribution of average fetal pulmonary trunk (PT) blood flow favors the ductus arteriosus (DA) over the lungs, the phasic aspects of this distribution during systole and diastole are not well understood. Accordingly, flow profile and wave intensity (WI) analyses were performed at baseline and during brief flow increases accompanying an extrasystole (ES) in 10 anesthetized late-gestation fetal sheep instrumented with PT, DA, and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes. At baseline, 83% of mean PT flow crossed the DA and 17% entered the lungs. However, early systolic flow associated with a forward-running compression wave (FCWis) was higher in the PA and predominant DA flow only emerged in midsystole when a large PA backward-running compression wave (BCWms), which reduced PA flow, was transmitted into the DA as a forward-running compression wave (FCWms) that increased flow. Subsequent protodiastolic forward DA flow occurring during pulmonary valve closure was associated with substantial retrograde PA flow, but insignificant PT flow. Conversely, forward DA flow in the remainder of diastole occurred with forward PT but near-zero PA flow. These flow and WI patterns, in conjunction with the results of mathematical modeling, suggest that 1) fetal PT flow preferentially passes into the PA during early systole due to a lower PA-than-DA characteristic impedance, while DA flow predominates in mid- and late systole due to flow effects arising from the PA BCWms, and 2) forward DA flow is mainly sustained by reversal of PA flow in protodiastole but discharge of a more central reservoir in diastole.


1996 ◽  
Vol 271 (2) ◽  
pp. H562-H570 ◽  
Author(s):  
V. M. Reddy ◽  
J. Wong ◽  
J. R. Liddicoat ◽  
M. Johengen ◽  
R. Chang ◽  
...  

To investigate early endothelial function associated with increased pulmonary blood flow, vascular shunts were placed between the ascending aorta and main pulmonary artery in 18 late-gestation fetal sheep. Four weeks after delivery, the lambs were instrumented to measure vascular pressures and blood flows, and blood was collected to measure plasma concentrations of guanosine 3',5'-cyclic monophosphate [cGMP, the second messenger to nitric oxide (NO)-mediated vasodilation] and L-arginine (the precursor for NO synthesis). The responses to the endothelium-dependent vasodilators acetylcholine (ACh, 1.0 microgram/kg) and ATP (0.1 mg.kg-1.min-1), the endothelium-independent vasodilators M & B-22948 (a cGMP-specific phosphodiesterase inhibitor, 2.5 mg/kg) and inhaled NO (40 ppm), and N omega-nitro-L-arginine (an inhibitor of NO synthase, 5 mg/kg) were then compared with responses in 12 age-matched controls. Vasodilator responses in control lambs were determined during pulmonary hypertension induced by U-46619 (a thromboxane A2 mimic). Shunted lambs displayed a selective impairment of endothelium-dependent pulmonary vasodilation, an augmented pulmonary vasoconstricting response to NO synthase inhibition, increased plasma cGMP concentrations, and decreased L-arginine concentrations. Taken together, these data suggest that lambs with pulmonary hypertension and increased pulmonary blood flow have early aberrations in endothelial function, as manifested by increased basal NO activity, that cannot be further increased by agonist-induced endothelium-dependent vasodilators.


1992 ◽  
Vol 70 (12) ◽  
pp. 1576-1582 ◽  
Author(s):  
Michelle P. Bendeck ◽  
B. Lowell Langille

We have measured total blood flows and blood flows per 100 g tissue to major tissues at 120 and 140 days gestation in fetal sheep and at 3 and 21 days of age in lambs (gestation period = 144 ± 2 days). Between 120 and 140 days gestation, flow per 100 g tissue increased by 74, 150, and 317% in the renal, intestinal, and hepatic arterial beds, but no further significant change in flow was observed at 3 or 21 days postpartum. Blood flows per 100 g to cerebral hemispheres and cerebellar tissues also increased dramatically during late gestation (142 and 121%, respectively), but declined sharply by 3 days postpartum (73 and 75%, respectively). Brain blood flows at 21 days postpartum remained substantially below late gestational levels. Adrenal blood flows per 100 g more than doubled during late gestation, fell by more than half at birth, and only partially recovered by 21 days of age. Blood flows to carcass tissues did not change in late gestation, fell at birth, then partially recovered. Pre- and post-natal increases in brain blood flows were almost entirely attributable to increased perfusion rather than tissue growth, whereas large perinatal increases in flow to the diaphragm paralleled tissue growth. Tissue growth and increased perfusion per 100 g contributed almost equally to increased blood flows to kidneys postnatally, and to adrenal glands and the gastrointestinal tract prenatally.Key words: blood flow, perinatal, birth, fetus, sheep.


2004 ◽  
Vol 55 (4) ◽  
pp. 568-575 ◽  
Author(s):  
David Ley ◽  
Gylfi Oskarsson ◽  
Mikael Bellander ◽  
Edgar Hernandez-Andrade ◽  
Göran Lingman ◽  
...  

2005 ◽  
Vol 564 (2) ◽  
pp. 575-588 ◽  
Author(s):  
Matthias Löhle ◽  
Thomas Müller ◽  
Carola Wicher ◽  
Marcus Roedel ◽  
Harald Schubert ◽  
...  

2008 ◽  
Vol 295 (4) ◽  
pp. H1505-H1513 ◽  
Author(s):  
Pierre Tourneux ◽  
Marc Chester ◽  
Theresa Grover ◽  
Steven H. Abman

In addition to high pulmonary vascular resistance (PVR) and low pulmonary blood flow, the fetal pulmonary circulation is characterized by mechanisms that oppose vasodilation. Past work suggests that high myogenic tone contributes to high PVR and may contribute to autoregulation of blood flow in the fetal lung. Rho-kinase (ROCK) can mediate the myogenic response in the adult systemic circulation, but whether high ROCK activity contributes to the myogenic response and modulates time-dependent vasodilation in the developing lung circulation are unknown. We studied the effects of fasudil, a ROCK inhibitor, on the hemodynamic response during acute compression of the ductus arteriosus (DA) in chronically prepared, late-gestation fetal sheep. Acute DA compression simultaneously induces two opposing responses: 1) blood flow-induced vasodilation through increased shear stress that is mediated by NO release and 2) stretch-induced vasoconstriction (i.e., the myogenic response). The myogenic response was assessed during acute DA compression after treatment with Nω-nitro-l-arginine, an inhibitor of nitric oxide synthase, to block flow-induced vasodilation and unmask the myogenic response. Intrapulmonary fasudil infusion (100 μg over 10 min) did not enhance flow-induced vasodilation during brief DA compression but reduced the myogenic response by 90% ( P < 0.05). During prolonged DA compression, fasudil prevented the time-dependent decline in left pulmonary artery blood flow at 2 h (183 ± 29 vs. 110 ± 11 ml/min with and without fasudil, respectively; P < 0.001). We conclude that high ROCK activity opposes pulmonary vasodilation in utero and that the myogenic response maintains high PVR in the normal fetal lung through ROCK activation.


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