Cerebrovascular effects of intravenous dopamine infusions in fetal sheep

2002 ◽  
Vol 92 (2) ◽  
pp. 717-724 ◽  
Author(s):  
Christine A. Gleason ◽  
Roderick Robinson ◽  
Andrew P. Harris ◽  
Dennis E. Mayock ◽  
Richard J. Traystman
Keyword(s):  
Blood Pressure ◽  
Sch 23390 ◽  
Adrenergic Blockade ◽  
Receptor Blockade ◽  
Fetal Sheep ◽  
Dopamine Infusion ◽  
Cerebral Vasoconstriction ◽  
Arterial Blood ◽  
Near Term ◽  
Few Data

Preterm infants are often treated with intravenous dopamine to increase mean arterial blood pressure (MAP). However, there are few data regarding cerebrovascular responses of developing animals to dopamine infusions. We studied eight near-term and eight preterm chronically catheterized unanesthetized fetal sheep. We measured cerebral blood flow and calculated cerebral vascular resistance (CVR) at baseline and during dopamine infusion at 2.5, 7.5, 25, and 75 μg · kg−1 · min−1. In preterm fetuses, MAP increased only at 75 μg · kg−1 · min−1 (25 ± 5%), whereas in near-term fetuses MAP increased at 25 μg · kg−1 · min−1 (28 ± 4%) and further at 75 μg · kg−1 · min−1 (51 ± 3%). Dopamine infusion was associated with cerebral vasoconstriction in both groups. At 25 μg · kg−1 · min−1, CVR increased 77 ± 51% in preterm fetuses and 41 ± 11% in near-term fetuses, and at 75 μg · kg−1 · min−1, CVR increased 80 ± 33% in preterm fetuses and 83 ± 21% in near-term fetuses. We tested these responses to dopamine in 11 additional near-term fetuses under α-adrenergic blockade (phenoxybenzamine, n = 5) and under dopaminergic D1-receptor blockade (SCH-23390, n = 6). Phenoxybenzamine completely blocked dopamine's pressor and cerebral vasoconstrictive effects, while D1-receptor blockade had no effect. Therefore, in unanesthetized developing fetuses, dopamine infusion is associated with cerebral vasoconstriction, which is likely an autoregulatory, α-adrenergic response to an increase in blood pressure.

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.

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.

Ontogeny of renal response to specific dopamine DA1-receptor stimulation in sheep

1992 ◽  
Vol 263 (4) ◽  
pp. R868-R873 ◽  
Author(s):  
J. L. Segar ◽  
F. G. Smith ◽  
E. N. Guillery ◽  
P. A. Jose ◽  
J. E. Robillard
Keyword(s):  
Sch 23390 ◽  
Plasma Renin ◽  
Fractional Excretion ◽  
Receptor Activation ◽  
Urinary Flow ◽  
Fetal Sheep ◽  
Plasma Aldosterone Concentration ◽  
Arterial Blood ◽  
Fractional Excretion Of Sodium ◽  
Near Term

The present study was designed to characterize the developmental changes in the renal responses to dopamine DA1-receptor activation in chronically instrumented preterm (109-115 days) and near-term (130-140 days, full term 145 days) fetal sheep. Cumulative doses of the selective DA1-agonist fenoldopam increased mean arterial blood pressure (MABP) in both preterm (+16 +/- 3%) and near-term fetuses (+16 +/- 3%) but had no significant effect on renal blood flow velocity. Infusion of the DA1-antagonist SCH-23390 did not affect the increase in MABP, suggesting that the effect of fenoldopam on MABP was not directly related to activation of DA1-receptors. Fenoldopam infusion had no significant effects on renal function parameters in preterm fetuses. In near-term fetuses, however, fenoldopam increased urinary flow rate (82.6 +/- 20.9%, P < 0.003), glomerular filtration rate (GFR; 16.6 +/- 4.9%, P < 0.01), urinary sodium excretion (40.1 +/- 14.9%, P < 0.02), and fractional excretion of sodium (26.8 +/- 11.2%, P < 0.03). Infusion of the DA1-antagonist SCH-23390 blocked the fenoldopam-induced diuresis and natriuresis but had no significant effect on the rise in GFR. Fenoldopam infusion had no significant effects on plasma renin activity and plasma aldosterone concentration and on urinary prostaglandin (PG) excretion (PGE2, PGF2 alpha, and 6-keto-PGF1 alpha). Taken together, these results suggest that the renal effect of DA1-receptor activation is age dependent and that stimulation of DA1-receptor in near-term fetuses is associated with a diuresis and natriuresis that seem to be independent of renal hemodynamics and adrenal effects.

scholarly journals Dopamine infusion for postresuscitation blood pressure support after profound asphyxia in near-term fetal sheep

2012 ◽  
Vol 98 (3) ◽  
pp. 699-709 ◽  
Author(s):  
Paul P. Drury ◽  
Lindsea C. Booth ◽  
Laura Bennet ◽  
Joanne O. Davidson ◽  
Bert Wibbens ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Pressure Support ◽  
Fetal Sheep ◽  
Dopamine Infusion ◽  
Near Term

Renal sympathetic nerve activity during asphyxia in fetal sheep

2012 ◽  
Vol 303 (1) ◽  
pp. R30-R38 ◽  
Author(s):  
Lindsea C. Booth ◽  
Simon C. Malpas ◽  
Carolyn J. Barrett ◽  
Sarah-Jane Guild ◽  
Alistair J. Gunn ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Fetal Sheep ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Arterial Blood ◽  
Near Term ◽  
Renal Sympathetic

The sympathetic nervous system (SNS) is an important mediator of fetal adaptation to life-threatening in utero challenges, such as asphyxia. Although the SNS is active well before term, SNS responses mature significantly over the last third of gestation, and its functional contribution to adaptation to asphyxia over this critical period of life remains unclear. Therefore, we examined the hypotheses that increased renal sympathetic nerve activity (RSNA) is the primary mediator of decreased renal vascular conductance (RVC) during complete umbilical cord occlusion in preterm fetal sheep (101 ± 1 days; term 147 days) and that near-term fetuses (119 ± 0 days) would have a more rapid initial vasomotor response, with a greater increase in RSNA. Causality of the relationship of RSNA and RVC was investigated using surgical (preterm) and chemical (near-term) denervation. All fetal sheep showed a significant increase in RSNA with occlusion, which was more sustained but not significantly greater near-term. The initial fall in RVC was more rapid in near-term than preterm fetal sheep and preceded the large increase in RSNA. These data suggest that although RSNA can increase as early as 0.7 gestation, it is not the primary determinant of RVC. This finding was supported by denervation studies. Interestingly, chemical denervation in near-term fetal sheep was associated with an initial fall in blood pressure, suggesting that by 0.8 gestation sympathetic innervation of nonrenal vascular beds is critical to maintain arterial blood pressure during the rapid initial adaptation to asphyxia.

Enhancement of the Antihypertensive Effect of Hydrochlorothiazide in Dogs after Suppression of Renin Release by Beta-Adrenergic Blockade

1975 ◽  
Vol 48 (2) ◽  
pp. 147-151
Author(s):  
C. S. Sweet ◽  
M. Mandradjieff
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Arterial Blood Pressure ◽  
Antihypertensive Effect ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
Antihypertensive Activity ◽  
Adrenergic Blockade ◽  
Arterial Blood

1. Renal hypertensive dogs were treated with hydrochlorothiazide (8−2 μmol/kg or 33 μmol/kg daily for 7 days), or timolol (4.6 μmol/kg daily for 4 days), a potent β-adrenergic blocking agent, or combinations of these drugs). Changes in mean arterial blood pressure and plasma renin activity were measured over the treatment period. 2. Neither drug significantly lowered arterial blood pressure when administered alone. Plasma renin activity, which did not change during treatment with timolol, was substantially elevated during treatment with hydrochlorothiazide. 3. When timolol was administered concomitantly with hydrochlorothiazide, plasma renin activity was suppressed and blood pressure was significantly lowered. 4. These observations suggest that compensatory activation of the renin-angiotensin system limits the antihypertensive activity of hydrochlorothiazide in renal hypertensive dogs and suppression of diuretic-induced renin release by timolol unmasks the antihypertensive effect of the diuretic.

Effects of hypercapnia and hypoxemia on fetal breathing after decortication

1986 ◽  
Vol 61 (3) ◽  
pp. 1071-1076 ◽  
Author(s):  
S. Ioffe ◽  
A. H. Jansen ◽  
V. Chernick
Keyword(s):  
Blood Pressure ◽  
Cerebral Cortex ◽  
Eye Movements ◽  
Duty Cycle ◽  
Chemical Control ◽  
Inspiratory Time ◽  
Obvious Effect ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Fetal Breathing

The effects of hypercapnia and hypoxemia on breathing movements were studied in 12 chronically decorticated fetal sheep, 127–140 days gestation. The fetal state of consciousness was defined in terms of activity of the lateral rectus and nuchal muscles. Arterial blood pressure was monitored. Fetal breathing was determined by integrated diaphragmatic electromyogram (EMG) and analyzed in terms of inspiratory time (TI), expiratory time (TE), electrical equivalent of tidal volume (EVT), breath interval (TT), duty cycle (TI/TT), mean inspiratory flow equivalent (EVT/TI), and instantaneous ventilation equivalent (EVT/TT). Fetal breathing occurred only during episodes of rapid-eye movements, and the response to hypercapnia consisted of an increase in EVT, TI, EVE, and EVT/TI and a decrease in the coefficient of variation of all measured parameters. Induction of hypoxia during episodes of spontaneous fetal breathing produced a decrease in the rate of breathing and an increase in EVT and TI with no change in the variability of all parameters studied. Since similar responses to hypercapnia and hypoxemia are seen in the intact fetus, we conclude that the cerebral cortex has no obvious effect on the chemical control of fetal breathing.

Insulin sensitivity and big ET-1 conversion to ET-1 after ETA- or ETB-receptor blockade in humans

2002 ◽  
Vol 93 (6) ◽  
pp. 2112-2121 ◽  
Author(s):  
Gunvor Ahlborg ◽  
Jonas Lindström
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Receptor Blockade ◽  
Receptor Stimulation ◽  
Renal Vasoconstriction ◽  
Arterial Blood ◽  
Etb Receptor

Cardiovascular diseases are characterized by insulin resistance and elevated endothelin (ET)-1 levels. Furthermore, ET-1 induces insulin resistance. To elucidate this mechanism, six healthy subjects were studied during a hyperinsulinemic euglycemic clamp during infusion of (the ET-1 precursor) big ET-1 alone or after ETA- or ETB-receptor blockade. Insulin levels rose after big ET-1 with or without the ETB antagonist BQ-788 ( P < 0.05) but were unchanged after the ETA antagonist BQ-123 + big ET-1. Infused glucose divided by insulin fell after big ET-1 with or without BQ-788 ( P < 0.05). Insulin and infused glucose divided by insulin values were normalized by ETA blockade. Mean arterial blood pressure rose during big ET-1 with or without BQ-788 ( P < 0.001) but was unchanged after BQ-123. Skeletal muscle, splanchnic, and renal blood flow responses to big ET-1 were abolished by BQ-123. ET-1 levels rose after big ET-1 ( P< 0.01) in a similar way after BQ-123 or BQ-788, despite higher elimination capacity after ETA blockade. In conclusion, ET-1-induced reduction in insulin sensitivity and clearance as well as splanchnic and renal vasoconstriction are ETA mediated. ETA-receptor stimulation seems to inhibit the conversion of big ET-1 to ET-1.

Sympathetic Neural Activation Evoked by μ-Receptor Blockade in Patients Addicted to Opioids Is Abolished by Intravenous Clonidine

2002 ◽  
Vol 96 (2) ◽  
pp. 346-351 ◽  
Author(s):  
Peter Kienbaum ◽  
Thorsten Heuter ◽  
Martin C. Michel ◽  
Norbert Scherbaum ◽  
Markus Gastpar ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Opioid Receptor ◽  
Sympathetic Activity ◽  
Plasma Concentrations ◽  
Mu Opioid Receptor ◽  
Receptor Blockade ◽  
Mu Opioid ◽  
Arterial Blood ◽  
Adrenoceptor Agonist ◽  
Alpha2 Adrenoceptor

Background Mu-opioid receptor blockade by naloxone administered for acute detoxification in patients addicted to opioids markedly increases catecholamine plasma concentrations, muscle sympathetic activity (MSA), and is associated with cardiovascular stimulation despite general anesthesia. The current authors tested the hypothesis that the alpha2-adrenoceptor agonist clonidine (1) attenuates increased MSA during mu-opioid receptor blockade for detoxification, and (2) prevents cardiovascular activation when given before detoxification. Methods Fourteen mono-opioid addicted patients received naloxone during propofol anesthesia. Clonidine (10 microg x kg(-1) administered over 5 min + 5 microg x kg(-1) x h(-1) intravenous) was infused either before (n = 6) or after (n = 6) naloxone administration. Two patients without immediate clonidine administration occurring after naloxone administration served as time controls. Muscle sympathetic activity (n = 8) in the peroneal nerve, catecholamine plasma concentrations (n = 14), arterial blood pressure, and heart rate were assessed in awake patients, during propofol anesthesia before and after mu-opioid receptor blockade, and after clonidine administration. Results Mu-receptor blockade markedly increased MSA from a low activity (burst frequency: from 2 burst/min +/- 1 to 24 +/- 8, means +/- SD). Similarly, norepinephrine (41 pg/ml +/- 37 to 321 +/- 134) and epinephrine plasma concentration (13 pg/ml +/- 6 to 627 +/- 146) significantly increased, and were associated with, increased arterial blood pressure and heart rate. Clonidine immediately abolished both increased MSA (P &lt; 0.001) and catecholamine plasma concentrations (P &lt; 0.001). When clonidine was given before mu-opioid receptor blockade, catecholamine plasma concentrations and hemodynamic variables did not change. Conclusions Administration of the alpha2-adrenoceptor agonist clonidine decreases both increased MSA and catecholamine plasma concentrations observed after mu-opioid receptor blockade for detoxification. Furthermore, clonidine pretreatment prevents the increase in catecholamine plasma concentration that otherwise occurs during mu-opioid receptor blockade.

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