Low-dose flunarizine does not affect short-term fetal circulatory responses to acute asphyxia in sheep near term

1998 ◽  
Vol 10 (5) ◽  
pp. 405 ◽  
Author(s):  
Yves Garnier ◽  
Richard Berger ◽  
Doris Pfeiffer ◽  
Arne Jensen
Keyword(s):  
Low Dose ◽  
Plasma Concentrations ◽  
Neuronal Cell ◽  
Cardiovascular Responses ◽  
Control Group ◽  
Short Term ◽  
Fetal Sheep ◽  
Physiological Variables ◽  
Arterial Blood ◽  
Near Term

Asphyxia is one of the major causes of perinatal brain damage and neuronal cell loss, which may result in psychomotor deficits during later development. It has been shown previously that the immature brain can be protected from ischemic injury by flunarizine, a class IV calcium antagonist. However, cardiovascular side-effects of flunarizine, when applied at the dosages used in those studies, have been reported. Recently, the present authors were able to demonstrate that even by injecting flunarizine at a far lower dosage (1 mg kg) estimated bodyweight) neuronal cell damage, caused by occlusion of both carotid arteries for 30 min, can be reduced in fetal sheep near term. The aim of the present study was, therefore, to examine whether low-dose flunarizine affects fetal cardiovascular responses to acute asphyxia in sheep near term. Ten fetal sheep were chronically instrumented at a mean gestational age of 132 1 days (term is at 147 days). Fetuses from the study group received a bolus injection of flunarizine (1 mg kg–1 estimated fetal weight) 60 min before asphyxia, whereas the solvent was administered to the fetuses from the control group. Organ blood flows, physiological variables and plasma concentrations of catecholamines were measured before, during and after a single occlusion of uterine blood flow for 2 min (i.e. at 0, 1, 2, 3, 4, and 30 min). Before asphyxia, the distribution of combined ventricular output and physiological variables, as well as concentrations of catecholamines, in fetuses from the control group were in the normal range for chronically prepared fetal sheep near term. During acute asphyxia there was a redistribution of cardiac output towards the central organs accompanied by a pronounced bradycardia and a rapid increase in arterial blood pressure. After asphyxia circulatory centralization did not resolve quite as rapidly as it developed, but was almost completely recovered at 30 min after the insult. There were nearly no differences in the time course of physiological and cardiovascular variables measured before, during and after acute intrauterine asphyxia between the control and study groups. From the present study it was concluded that low-dose flunarizine does not affect short-term fetal circulatory responses to acute asphyxia in sheep near term.

Effect of human recombinant superoxide dismutase on canine myocardial infarction

1990 ◽  
Vol 258 (2) ◽  
pp. H369-H380 ◽  
Author(s):  
B. S. Patel ◽  
M. O. Jeroudi ◽  
P. G. O'Neill ◽  
R. Roberts ◽  
R. Bolli
Keyword(s):  
Superoxide Dismutase ◽  
Infarct Size ◽  
Low Dose ◽  
Coronary Occlusion ◽  
Plasma Concentrations ◽  
Control Group ◽  
High Dose ◽  
Collateral Flow ◽  
Tetrazolium Chloride ◽  
Arterial Blood

To determine whether human recombinant superoxide dismutase (h-SOD) produces sustained reduction of infarct size, anesthetized dogs underwent a 2-h coronary occlusion followed by either 48 or 4 h of reperfusion. In the 48-h study, dogs were randomized to three intravenous treatments: 1) “low-dose” h-SOD (2 mg/kg bolus 2 min before reperfusion followed by 4 mg/kg over 45 min), 2) “high-dose” h-SOD (8 mg/kg bolus 2 min before reperfusion followed by 8 mg/kg over 45 min), or 3) equivalent volumes of saline. In the 4-h study, dogs were randomized to high-dose h-SOD or saline. Occluded bed size was measured by postmortem perfusion and infarct size by triphenyl tetrazolium chloride staining and planimetry. Investigators performing the study and measuring infarct size were blinded to the treatment given. High plasma concentrations of h-SOD were present in the arterial blood of treated dogs in the early phase of reperfusion (greater than 60 and greater than 180 micrograms/ml in low- and high-dose groups, respectively). In both studies, control and treated groups were similar with respect to occluded bed size, collateral blood flow, and rate-pressure product during ischemia. In the 48-h study, infarct size, expressed as percent of occluded bed size, was 41.3 +/- 7.6% (mean +/- SE) in the control group, 37.1 +/- 7.2% in the low-dose h-SOD group, and 48.0 +/- 7.1% in the high-dose h-SOD group. In the 4-h study, infarct size was 30.6 +/- 4.9% in the control group and 31.5 +/- 9.6% in the high-dose h-SOD group. Analysis of the flow-infarct relationships confirmed that h-SOD did not reduce infarct size at any level of collateral flow in either the 48- or 4-h study. Recovery of regional myocardial function after reperfusion was also unaffected by h-SOD in both studies. Thus in this randomized blinded study, large doses of h-SOD given at the time of reperfusion failed to limit infarct size or enhance recovery of function, both early (4 h) and late (48 h) after reperfusion following a 2-h coronary occlusion.

Renal, hormonal, and cardiovascular responses to chronic angiotensin I infusion in the ovine fetus

1997 ◽  
Vol 272 (6) ◽  
pp. R1912-R1917 ◽  
Author(s):  
K. M. Moritz ◽  
K. Tangalakis ◽  
E. M. Wintour
Keyword(s):  
Plasma Concentrations ◽  
Allantoic Fluid ◽  
Cardiovascular Responses ◽  
Urine Flow ◽  
Angiotensin I ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Urine Production ◽  
Fetal Urine ◽  
Ovine Fetus

Long-term infusion of angiotensin I (ANG I) into the ovine fetus has been shown to cause excess accumulation of fetal fluid in the allantoic compartment. It was hypothesized that this resulted from sustained increases in fetal urine production, and the hormonal basis was examined. ANG I (6.7 micrograms/h, n = 6) or isotonic saline (n = 6) was infused for 3 days into chronically cannulated ovine fetuses (112-122 days of gestation). ANG I caused an immediate and progressive increase in mean arterial blood pressure (from 42 +/- 2 to 57 +/- 4 mmHg), increased urine flow rate (from 15 +/- 3 to 48 +/- 8 ml/h), and increased glomerular filtration rate (from 97 +/- 15 to 146 +/- 24 ml/h), without significant changes in fetal plasma concentrations of aldosterone, atrial natriuretic factor (ANF), adrenocorticotropin, or cortisol. There were substantial increases in sodium and chloride excretion, due to both increased fetal urine concentrations and fetal urine flow, without significant changes in urine osmolality (from 134 +/- 9 to 147 +/- 12 mosmol/kg water). There were no significant changes in any parameter in the saline-infused fetuses. Neither amniotic or allantoic fluid volume was significantly changed by ANG I infusion, but allantoic fluid Cl- concentration increased significantly. The conclusions are that ANG I caused a diuresis and natriuresis in the fetal sheep independent of changes in cortisol or ANF.

Effect of atrial natriuretic factor on release of arginine vasopressin and renin in fetal lambs

1994 ◽  
Vol 267 (4) ◽  
pp. R984-R989
Author(s):  
D. D. Berry ◽  
R. K. Jaekle ◽  
J. C. Rose
Keyword(s):  
Arginine Vasopressin ◽  
Atrial Natriuretic Factor ◽  
Low Dose ◽  
Plasma Concentrations ◽  
Fold Increase ◽  
High Dose ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

The purpose of this study was to determine the effect of increased plasma atrial natriuretic factor (ANF) concentrations on the arginine vasopressin (AVP) and renin response to arterial hypotension in fetal sheep. Lamb fetuses at 123-133 days of gestation were infused intravascularly with 0.9% NaCl and ANF at 25 ng.kg-1.min-1 (low dose) or NaCl and ANF at 250 ng.kg-1.min-1 (high dose) for 115 min. After 45 min, sodium nitroprusside was infused for 10 min to yield a 25% decrease in mean arterial blood pressure. ANF infusions resulted in plasma concentrations of 150-200 and 500-800 pg/ml in the low-dose and high-dose groups, respectively. In both the low-dose and high-dose ANF groups, AVP and renin concentrations increased in response to hypotension. In the low-dose ANF group, there was no difference in this response between ANF and control lambs. Compared with controls, a high dose of ANF resulted in an elevated basal level of AVP (1.6 +/- 0.04 vs. 12.3 +/- 6.7 pg/ml) and an 11-fold increase of AVP at 10 min of hypotension (12.2 +/- 5.6 vs. 134.9 +/- 36.1 pg/ml). Basal and stimulated renin concentrations were unchanged by the high-dose ANF infusion. This study demonstrates that in the fetal lamb, ANF concentrations of 500-800 pg/ml augment the basal and stimulated release of AVP but do not affect the renin response.

scholarly journals Fetal Hypothalamus-Pituitary-Adrenal Responses to Estradiol Sulfate

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4966-4973 ◽  
Author(s):  
Charles E. Wood
Keyword(s):  
Fetal Brain ◽  
Control Group ◽  
Cortisol Secretion ◽  
Acth Secretion ◽  
Fetal Sheep ◽  
Adrenal Axis ◽  
Arterial Blood ◽  
Hypothalamus Pituitary Adrenal Axis ◽  
Near Term ◽  
Pituitary Adrenal Axis

Estradiol (E2) is an important modifier of the activity of the fetal hypothalamus-pituitary-adrenal axis. We have reported that estradiol-3-sulfate (E2SO4) circulates in fetal blood in far higher concentrations than E2 and that the fetal brain expresses steroid sulfatase, required for local deconjugation of E2SO4. We performed the present study to test the hypothesis that chronic infusion of E2SO4 chronically increases ACTH and cortisol secretion and that it shortens gestation. Chronically catheterized fetal sheep were treated with E2SO4 intracerebroventricular (n = 5), E2SO4 iv (n = 4), or no steroid infusion (control group, n = 5). Fetuses were subjected to arterial blood sampling every other day until spontaneous birth for plasma hormone analysis. Treatment with E2SO4 attenuated preparturient increases in ACTH secretion near term without affecting the ontogenetic rise in plasma cortisol. Infusion of E2SO4 intracerebroventricularly significantly increased plasma E2, plasma E2SO4, and plasma progesterone and shortened gestation compared with all other groups. These results are consistent with the conclusion that E2SO4: 1) interacts with the hypothalamus-pituitary-adrenal axis primarily by stimulating cortisol secretion and inhibiting ACTH and pro-ACTH secretion by negative feedback; and 2) stimulates the secretion of E2 and E2SO4. We conclude that the endocrine response to E2SO4 in the fetus is not identical with the response to E2.

Peripheral chemoreflex activation and cardiac function during hypoxemia in near term fetal sheep without placental compromise

2021 ◽  
Author(s):  
Juulia Lantto ◽  
Tiina Erkinaro ◽  
Mervi Haapsamo ◽  
Heikki Huhta ◽  
Leena Alanne ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Carotid Artery ◽  
Arterial Oxygen ◽  
Sheep Model ◽  
Fetal Sheep ◽  
Descending Aorta ◽  
Arterial Blood ◽  
Near Term ◽  
Peripheral Chemoreflex

A drop in arterial oxygen content activates fetal chemoreflex including an increase in sympathetic activity leading to peripheral vasoconstriction and redistribution of blood flow to protect the brain, myocardium, and adrenal glands. By using a chronically instrumented fetal sheep model with intact placental circulation at near-term gestation, we investigated the relationship between peripheral chemoreflex activation induced by hypoxemia and central hemodynamics. 17 Åland landrace sheep fetuses at 115-128/145 gestational days were instrumented. Carotid artery was catheterised in 10 fetuses and descending aorta in 7 fetuses. After a 4-day recovery, baseline measurements of fetal arterial blood pressures, blood gas values, and fetal cardiovascular hemodynamics by pulsed Doppler ultrasonography were obtained under isoflurane-anesthesia. Comparable data to baseline was collected 10 (acute hypoxemia) and 60 minutes (prolonged hypoxemia) after maternal hypo-oxygenation to saturation level of 70-80% was achieved. During prolonged hypoxemia, pH and base excess (BE) were lower, and lactate levels higher in the descending aorta than in the carotid artery. During hypoxemia mean arterial blood pressure (MAP) in the descending aorta increased, while in the carotid artery MAP decreased. In addition, right pulmonary artery pulsatility index values increased, and the diastolic component in the aortic isthmus blood flow velocity waveform became more retrograde. Both fetal ventricular cardiac outputs were maintained even during prolonged hypoxemia when significant fetal metabolic acidemia developed. Fetal chemoreflex activation induced by hypoxemia decreased the perfusion pressure in the cerebral circulation. Fetal weight-indexed LVCO or AoI Net Flow-ratio did not correlate with a drop in carotid artery blood pressure.

Fetal breathing, sleep state, and cardiovascular responses to graded anemia in sheep

1987 ◽  
Vol 63 (4) ◽  
pp. 1463-1468 ◽  
Author(s):  
B. J. Koos ◽  
H. Sameshima ◽  
G. G. Power
Keyword(s):  
Eye Movements ◽  
Cardiovascular Responses ◽  
Severe Anemia ◽  
Sleep State ◽  
Fetal Sheep ◽  
Rapid Eye Movements ◽  
Mild Anemia ◽  
Arterial Blood ◽  
Moderate Anemia ◽  
Pressure Changes

Graded anemia was produced for 2 h in 10 unanesthetized fetal sheep by infusing plasma in exchange for fetal blood. This reduced the mean fetal hematocrits during the 1st h of anemia to 19.7 +/- 0.5% [control (C) = 28.2 +/- 1.1%] for mild anemia, 17.4 +/- 0.9% (C = 30.0 +/- 1.1%) for moderate anemia, and 15.1 +/- 1.0% (C = 29.2 +/- 1.3%) for severe anemia. The respective mean arterial O2 contents (CaO2) were 4.46 +/- 0.20, 3.89 +/- 0.24, and 3.22 +/- 0.19 ml/dl. Mean arterial PO2 was reduced significantly (by 2 Torr) only during moderate anemia, and mean arterial pH was decreased only during severe anemia. No significant changes occurred in arterial PCO2. Fetal tachycardia occurred during anemia. Mean arterial pressure was reduced by 2–3 mmHg during mild anemia; however, no significant blood pressure changes were observed for moderate or severe anemia. The incidence of rapid-eye movements and breathing activity was not affected by mild anemia, but the incidence of both was reduced significantly during moderate and severe anemia. It is concluded that 1) a reduction in CaO2 of greater than 2.48 +/- 0.22 ml/dl by hemodilution inhibits rapid-eye movements and breathing activity, and 2) the PO2 signal for inhibition does not come from arterial blood but from lower PO2 in tissue.

scholarly journals Dopamine does not limit fetal cerebrovascular responses to hypoxia

2007 ◽  
Vol 102 (1) ◽  
pp. 130-134 ◽  
Author(s):  
Dennis E. Mayock ◽  
Rachel Bennett ◽  
Roderick D. Robinson ◽  
Christine A. Gleason
Keyword(s):  
Infusion Rate ◽  
Perfusion Pressure ◽  
High Dose ◽  
Fetal Hypoxia ◽  
Fetal Sheep ◽  
Dopamine Infusion ◽  
Cerebrovascular Resistance ◽  
Arterial Blood ◽  
Cerebral Vasodilatation ◽  
Near Term

Dopamine is used clinically to stabilize mean arterial blood pressure (MAP) in sick infants. One goal of this therapeutic intervention is to maintain adequate cerebral blood flow (CBF) and perfusion pressure. High-dose intravenous dopamine has been previously demonstrated to increase cerebrovascular resistance (CVR) in near-term fetal sheep. We hypothesized that this vascular response might limit cerebral vasodilatation during acute isocapnic hypoxia. We studied nine near-term chronically catheterized unanesthetized fetal sheep. Using radiolabeled microspheres to measure fetal CBF, we calculated CVR at baseline, during fetal hypoxia, and then with the addition of an intravenous dopamine infusion at 2.5, 7.5, and 25 μg·kg−1·min−1 while hypoxia continued. During acute isocapnic fetal hypoxia, CBF increased 73.0 ± 14.1% and CVR decreased 38.9 ± 4.9% from baseline. Dopamine infusion at 2.5 and 7.5 μg·kg−1·min−1, begun during hypoxia, did not alter CVR or MAP, but MAP increased when dopamine infusion was increased to 25 μg·kg−1·min−1. Dopamine did not alter CBF or affect the CBF response to hypoxia at any dose. However, CVR increased at a dopamine infusion rate of 25 μg·kg−1·min−1. This increase in CVR at the highest dopamine infusion rate is likely an autoregulatory response to the increase in MAP, similar to our previous findings. Therefore, in chronically catheterized unanesthetized near-term fetal sheep, dopamine does not alter the expected cerebrovascular responses to hypoxia.

scholarly journals Effect of different levels of short-term feed intake on folliculogenesis and follicular fluid and plasma concentrations of lactate dehydrogenase, glucose, and hormones in Hu sheep during the luteal phase

Reproduction ◽  
2011 ◽  
Vol 142 (5) ◽  
pp. 699-710 ◽  
Author(s):  
Shijia Ying ◽  
Ziyu Wang ◽  
Changlong Wang ◽  
Haitao Nie ◽  
Dongyang He ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Estrous Cycle ◽  
Follicular Fluid ◽  
Plasma Concentrations ◽  
Insulin Level ◽  
Control Group ◽  
Short Term ◽  
Circulating Levels ◽  
Hu Sheep ◽  
Different Levels

This study investigated the effects of short-term food restriction or supplementation on folliculogenesis and plasma and intrafollicular metabolite and hormone concentrations. Ewes were randomly assigned to three groups: the control group received a maintenance diet (M) while the supplemented group and restricted group received 1.5×M and 0.5×M respectively on days 6–12 of their estrous cycle. Estrus was synchronized by intravaginal progestogen sponges for 12 days. On days 7–12, blood samples were taken. After slaughter, the ovarian follicles were classified and the follicular fluid was collected. Compared with restriction, supplementation shortened the estrous cycle length, decreased the number of follicles 2.5–3.5 mm and follicular fluid estradiol (E2) concentration, increased the number of follicles >3.5 mm and plasma glucose, insulin and glucagon concentrations, and augmented the volume of follicles >2.5 mm. Restricted ewes had higher intrafollicular insulin concentration, but it was similar to that of supplemented ewes. Compared with follicles ≤2.5 mm, the intrafollicular glucose and E2concentrations were increased and the testosterone, insulin, and glucagon concentrations and lactate dehydrogenase (LDH) activity were decreased in follicles >2.5 mm. Only in restricted ewes were intrafollicular LDH and testosterone concentrations in follicles ≤2.5 mm not different from those in follicles ≤2.5 mm. In conclusion, the mechanism by which short-term dietary restriction inhibits folliculogenesis may involve responses to intrafollicular increased E2, testosterone, and LDH levels in late-stage follicles. This may not be due to the variation of intrafollicular insulin level but rather due to decreased circulating levels of glucose, insulin, and glucagon.

scholarly journals Male disadvantage? Fetal sex and cardiovascular responses to asphyxia in preterm fetal sheep

2007 ◽  
Vol 293 (3) ◽  
pp. R1280-R1286 ◽  
Author(s):  
Laura Bennet ◽  
Lindsea C. Booth ◽  
Noha Ahmed-Nasef ◽  
Justin M. Dean ◽  
Joanne Davidson ◽  
...  
Keyword(s):  
Cohort Analysis ◽  
Cardiovascular Responses ◽  
Normal Weight ◽  
Premature Delivery ◽  
Vascular Conductance ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Retrospective Cohort Analysis ◽  
Femoral Blood Flow ◽  
Full Occlusion

Clinically and experimentally male fetuses are at significantly greater risk of dying or suffering injury at birth, particularly after premature delivery. We undertook a retrospective cohort analysis of 60 female and 65 male singleton preterm fetal sheep (103–104 days, 0.7 gestation) with mean arterial blood pressure (MAP), heart rate, and carotid and femoral blood flow recordings during 25 min of umbilical cord occlusion in utero. Occlusions were stopped early if fetal MAP fell below 8 mmHg or if there was asystole for >20 s. Fetuses that were able to complete the full 25-min period of occlusion showed no differences between sexes for any cardiovascular responses. Similar numbers of occlusions were stopped early in males (mean: 21 min, n = 16) and females (mean: 23 min, n = 16); however, they showed different responses. Short-occlusion males ( n = 16) showed a slower initial fall in femoral vascular conductance, followed by greater bradycardia, hypotension, and associated organ hypoperfusion compared with full-occlusion fetuses. In contrast, short-occlusion females ( n = 16) showed a significantly more rapid early increase in femoral vascular conductance than the full-occlusion fetuses, followed by worsening of bradycardia and hypotension that was intermediate to the full-occlusion fetuses and short-occlusion males. Among all fetuses, MAP at 15 min of occlusion, corresponding with the time of the maximal rate of fall, was correlated with postmortem weight in males ( R2 = 0.07) but not females. In conclusion, male and female fetuses showed remarkably similar chemoreflex and hemodynamic responses to severe asphyxia, but some males did show impaired hemodynamic adaptation within the normal weight range.

Biphasic changes in fetal heart rate variability in preterm fetal sheep developing hypotension after acute on chronic lipopolysaccharide exposure

2014 ◽  
Vol 307 (4) ◽  
pp. R387-R395 ◽  
Author(s):  
Christopher A. Lear ◽  
Joanne O. Davidson ◽  
Lindsea C. Booth ◽  
Guido Wassink ◽  
Robert Galinsky ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Fetal Heart Rate ◽  
Low Dose ◽  
Fetal Heart ◽  
Transient Increase ◽  
Electromyographic Activity ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Fetal Heart Rate Variability

Perinatal exposure to infection is highly associated with adverse outcomes. Experimentally, acute, severe exposure to gram-negative bacterial lipopolysaccharide (LPS) is associated with increased fetal heart rate variability (FHRV). It is unknown whether FHRV is affected by subclinical infection with or without acute exacerbations. We therefore tested the hypothesis that FHRV would be associated with hypotension after acute on chronic exposure to LPS. Chronically instrumented fetal sheep at 0.7 gestation were exposed to a continuous low-dose LPS infusion ( n = 12, 100 ng/kg over 24 h, followed by 250 ng·kg−1·24 h−1 for a further 96 h) or the same volume of saline ( n = 10). Boluses of either 1 μg LPS or saline were given at 48, 72, and 96 h. Low-dose infusion was not associated with hemodynamic or FHRV changes. The first LPS bolus was associated with tachycardia and suppression of nuchal electromyographic activity in all fetuses. Seven of twelve fetuses developed hypotension (a fall in mean arterial blood pressure ≥5 mmHg). FHRV was transiently increased only at the onset of hypotension, in association with increased cytokine induction and electroencephalogram suppression. FHRV then fell before the nadir of hypotension, with transient suppression of short-term FHRV. After the second LPS bolus, the hypotension group showed a biphasic pattern of a transient increase in FHRV followed by more prolonged suppression. These findings suggest that infection-related hypotension in the preterm fetus mediates the transient increase in FHRV and that repeated exposure to LPS leads to progressive loss of FHRV.

Sign in / Sign up

Export Citation Format

Share Document