Preexisting hypoxia is associated with a delayed but more sustained rise in T/QRS ratio during prolonged umbilical cord occlusion in near-term fetal sheep

2007 ◽  
Vol 293 (3) ◽  
pp. R1287-R1293 ◽  
Author(s):  
Bert Wibbens ◽  
Laura Bennet ◽  
Jenny A. Westgate ◽  
Harmen H. De Haan ◽  
Guido Wassink ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Troponin T ◽  
Limited Information ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Femoral Blood Flow ◽  
Transient Rise ◽  
Profound Hypotension ◽  
Femoral Blood ◽  
Near Term

There is limited information about whether preexisting fetal hypoxia alters hemodynamic responses and changes in T/QRS ratio and ST waveform shape during subsequent severe asphyxia. Chronically instrumented near-term sheep fetuses (124 ± 1 days) were identified as either normoxic PaO2 > 17 mmHg ( n = 9) or hypoxic PaO2 ≤ 17 mmHg ( n = 5); then they received complete occlusion of the umbilical cord for 15 min. Umbilical cord occlusion led to sustained bradycardia, severe acidosis, and transient hypertension followed by profound hypotension in both groups. Preexisting hypoxia did not affect changes in mean arterial blood pressure but was associated with a more rapid initial fall in femoral blood flow and vascular conductance and with transiently higher fetal heart rate at 2 min and from 9 to 11 min of occlusion compared with previously normoxic fetuses. Occlusion was associated with a significant but transient rise in T/QRS ratio; preexisting hypoxia was associated with a significant delay in this rise (maxima 3.7 ± 0.4 vs. 6.2 ± 0.5 min), but a slower rate of fall. There was a similar elevation in troponin-T levels 6 h after occlusion in the two groups [median (range) 0.43 (0.08, 1.32) vs. 0.55 (0.16, 2.32) μg/l, not significant]. In conclusion, mild preexisting hypoxia in normally grown singleton fetal sheep is associated with more rapid centralization of circulation after umbilical cord occlusion and delayed elevation of the ST waveform and slower fall, suggesting that chronic hypoxia alters myocardial dynamics during asphyxia.

The ontogeny of hemodynamic responses to prolonged umbilical cord occlusion in fetal sheep

2007 ◽  
Vol 103 (4) ◽  
pp. 1311-1317 ◽  
Author(s):  
Guido Wassink ◽  
Laura Bennet ◽  
Lindsea C. Booth ◽  
Ellen C. Jensen ◽  
Bert Wibbens ◽  
...  
Keyword(s):  
Blood Flow ◽  
Umbilical Cord ◽  
Rapid Onset ◽  
Hemodynamic Responses ◽  
Fetal Sheep ◽  
Eeg Activity ◽  
Progressive Development ◽  
Arterial Blood ◽  
Femoral Blood Flow ◽  
Femoral Blood

There is evidence that preterm fetuses have blunted chemoreflex-mediated responses to hypoxia. However, the preterm fetus has much lower aerobic requirements than at term, and so moderate hypoxia may not be sufficient to elicit maximal chemoreflex responses; there are only limited quantitative data on the ontogeny of chemoreflex and hemodynamic responses to severe asphyxia. Chronically instrumented fetal sheep at 0.6 ( n = 12), 0.7 ( n = 12), and 0.85 ( n = 8) of gestational age (GA; term = 147 days) were exposed to 30, 25, or 15 min of complete umbilical cord occlusion, respectively. At all ages, occlusion was associated with early onset of bradycardia, profoundly reduced femoral blood flow and conductance, and hypertension. The 0.6-GA fetuses showed a significantly slower and lesser fall in femoral blood flow and conductance compared with the 0.85-GA group, with a correspondingly reduced relative rise in mean arterial blood pressure. As occlusion continued, the initial adaptation was followed by loss of peripheral vasoconstriction and progressive development of hypotension in all groups. The 0.85-GA fetuses showed significantly more sustained reduction in femoral conductance but also more rapid onset of hypotension than either of the younger groups. Electroencephalographic (EEG) activity was suppressed during occlusion in all groups, but the degree of suppression was less at 0.6 GA than at term. In conclusion, the near-midgestation fetus shows attenuated initial (chemoreflex) peripheral vasomotor responses to severe asphyxia compared with more mature fetuses but more sustained hemodynamic adaptation and reduced suppression of EEG activity during continued occlusion of the umbilical cord.

Acute on chronic exposure to endotoxin is associated with enhanced chemoreflex responses in preterm fetal sheep

2013 ◽  
Vol 304 (10) ◽  
pp. R799-R803 ◽  
Author(s):  
Lindsea C. Booth ◽  
Paul P. Drury ◽  
Cameron Muir ◽  
Ellen C. Jensen ◽  
Alistair J. Gunn ◽  
...  
Keyword(s):  
Blood Flow ◽  
Umbilical Cord ◽  
Chronic Exposure ◽  
Fetal Sheep ◽  
Hypoxic Injury ◽  
Arterial Blood ◽  
Femoral Blood Flow ◽  
Dose Infusion ◽  
Initial Hypothesis ◽  
Femoral Blood

There is increasing evidence that exposure to infection can sensitize the fetus to subsequent hypoxic injury. However, it is unclear whether this involves compromise of the fetal cardiovascular adaptation to acute asphyxia. Chronically instrumented 103-day-old (0.7 gestational age, term is 147 days) fetal sheep in utero were randomized to receive either gram-negative lipopolysaccharide (LPS) as a continuous low-dose infusion for 120 h plus boluses of 1 μg LPS at 48, 72, and 96 h with asphyxia at 102 h (i.e., 6 h after the final LPS bolus) induced by umbilical cord occlusion for 15 min (LPS treated, n = 8), or the same volume of saline plus occlusion (saline treated, n = 7). Fetuses were killed 5 days after occlusion. LPS was associated with a more rapid fall in fetal heart rate at the onset of occlusion ( P < 0.05) and with minimally lower values during occlusion ( P < 0.05). The LPS-treated fetuses had lower fetal mean arterial blood pressure (BP) and greater carotid artery blood flow (CaBF) before occlusion ( P < 0.05) but showed an increase in BP and fall in CaBF to similar values as saline controls during occlusion. There were no differences between the groups in femoral blood flow before or during occlusion. Contrary to our initial hypothesis, acute on chronic exposure to LPS was associated with more rapid cardiovascular adaptation to umbilical cord occlusion.

Fetal acidosis and hypotension during repeated umbilical cord occlusions are associated with enhanced chemoreflex responses in near-term fetal sheep

2005 ◽  
Vol 99 (4) ◽  
pp. 1477-1482 ◽  
Author(s):  
Laura Bennet ◽  
Jenny A. Westgate ◽  
Yung-Chi (“Jack”) Liu ◽  
Guido Wassink ◽  
Alistair J. Gunn
Keyword(s):  
Umbilical Cord ◽  
Fetal Heart ◽  
Severe Hypoxia ◽  
Acid Base ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Acid Base Status ◽  
Near Term ◽  
Fetal Acidosis ◽  
Fetal Compromise

This study examined the hypothesis that repeated episodes of brief but severe hypoxia would not attenuate the chemoreflex-mediated rapid initial fall in fetal heart rate (FHR) and, further, that greater hypoxic stress, as shown by hypotension and metabolic acidosis, would be associated with an enhanced chemoreflex response. Chronically instrumented, near-term fetal sheep received 1 min total umbilical cord occlusion either every 5 min for 4 h (1:5 group; n = 8) or every 2.5 min (1:2.5 group; n = 8) until mean arterial blood pressure fell to <20 mmHg on two successive occlusions. Umbilical cord occlusion caused variable decelerations, with sustained hypertension in the 1:5 group and little change in acid-base status (pH 7.34 ± 0.03 after 4 h). In contrast, the 1:2.5 group showed progressive hypotension and metabolic acidemia (pH 6.92 ± 0.04 after the last occlusion). The 1:2.5 group showed a significant increase in the rate of initial fall in FHR during the occlusion series, which was greater than the 1:5 group in the last 30 min of the occlusion series (9.4 ± 1.4 vs. 3.5 ± 0.3 beats·min−1·s−1; P < 0.01), with a greater fall in FHR (71.9 ± 6.5 vs. 47.0 ± 8.7 beats/min; P < 0.05). In summary, this study demonstrated that repetitive laborlike cord occlusions, which led to severe fetal compromise, were associated with an increase in the slope and magnitude of the initial FHR deceleration. These findings support the concept of the chemoreflex as a central, robust component of fetal adaptation to severe hypoxia.

Lack of evidence for impaired preload or Bezold-Jarisch activation during brief umbilical cord occlusions in fetal sheep

2021 ◽  
Author(s):  
Christopher A. Lear ◽  
Laura Bennet ◽  
Benjamin S. A. Lear ◽  
Jenny A. Westgate ◽  
Alistair Jan Gunn
Keyword(s):  
Blood Flow ◽  
Umbilical Cord ◽  
Cardiovascular Responses ◽  
Diastolic Filling ◽  
Fetal Sheep ◽  
Blood Flows ◽  
Rapid Fall ◽  
Filling Time ◽  
Cervical Vagotomy ◽  
Femoral Blood

Impaired cardiac preload secondary to umbilical cord occlusion (UCO) has been hypothesized to contribute to intrapartum decelerations, brief falls in fetal heart rate (FHR), through the activation of the Bezold-Jarisch reflex. This cardioprotective reflex increases parasympathetic and inhibits sympathetic outflows triggering hypotension, bradycardia and peripheral vasodilation but its potential to contribute to intrapartum decelerations has never been systematically examined. In this study we performed bilateral cervical vagotomy to remove the afferent arm and the efferent parasympathetic arm of the Bezold-Jarisch reflex. 22 chronically instrumented fetal sheep at 0.85 of gestation received vagotomy (n=7) or sham-vagotomy (control, n=15), followed by three 1-min complete UCOs separated by 4-min reperfusion periods. UCOs in control fetuses were associated with a rapid fall in FHR and reduced femoral blood flow mediated by intense femoral vasoconstriction, leading to hypertension. Vagotomy abolished the rapid fall in FHR (p<0.001), and despite reduced diastolic filling time, increased both carotid (p<0.001) and femoral (p<0.05) blood flow during UCOs, secondary to carotid vasodilation (p<0.01) and delayed femoral vasoconstriction (p<0.05). Finally, vagotomy was associated with an attenuated rise in cortical impedance during UCOs (p<0.05), consistent with improved cerebral substrate supply. In conclusion, increased carotid and femoral blood flows after vagotomy are consistent with increased left and right ventricular output, which is incompatible with the hypothesis that labor-like UCOs impair ventricular filling. Overall, the cardiovascular responses to vagotomy do not support the hypothesis that the Bezold-Jarisch reflex is activated by UCO. The Bezold-Jarisch reflex is therefore mechanistically unable to contribute to intrapartum decelerations.

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.

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.

scholarly journals Sex differences in leg vasodilation during graded knee extensor exercise in young adults

2007 ◽  
Vol 103 (5) ◽  
pp. 1583-1591 ◽  
Author(s):  
Beth A. Parker ◽  
Sandra L. Smithmyer ◽  
Justin A. Pelberg ◽  
Aaron D. Mishkin ◽  
Michael D. Herr ◽  
...  
Keyword(s):  
Blood Flow ◽  
Femoral Artery ◽  
Knee Extensor ◽  
Activity Levels ◽  
Vascular Conductance ◽  
Arterial Blood ◽  
Vasodilatory Response ◽  
Femoral Blood Flow ◽  
Femoral Blood ◽  
Response To Exercise

Limb vascular conductance responses to pharmacological and nonexercise vasodilator stimuli are generally augmented in women compared with men. In the present investigation, we tested the hypothesis that exercise-induced vasodilator responses are also greater in women than men. Sixteen women and 15 men (20–30 yr) with similar fitness and activity levels performed graded quadriceps exercise (supine, single-leg knee extensions, 40 contractions/min) to maximal exertion. Active limb hemodynamics (left common femoral artery diameter and volumetric blood flow), heart rate (ECG), and beat-to-beat mean arterial blood pressure (MAP; radial artery tonometry) were measured during each 3-min workload (4.8 and 8 W/stage for women and men, respectively). The hyperemic response to exercise (slope of femoral blood flow vs. workload) was greater ( P < 0.01) in women as was femoral blood flow at workloads >15 W. The leg vasodilatory response to exercise (slope of calculated femoral vascular conductance vs. absolute workload) was also greater in women than in men ( P < 0.01) because of the sex difference in hyperemia and the women's lower MAP (∼10–15 mmHg) at all workloads ( P < 0.05). The femoral artery dilated to a significantly greater extent in the women (∼0.5 mm) than in the men (∼0.1 mm) across all submaximal workloads. At maximal exertion, femoral vascular conductance was lower in the men (men, 18.0 ± 0.6 ml·min−1·mmHg−1; women, 22.6 ± 1.4 ml·min−1·mmHg−1; P < 0.01). Collectively, these findings suggest that the vasodilatory response to dynamic leg exercise is greater in young women vs. men.

Profound hypotension and associated electrocardiographic changes during prolonged cord occlusion in the near term fetal sheep

2005 ◽  
Vol 193 (3) ◽  
pp. 803-810 ◽  
Author(s):  
Bert Wibbens ◽  
Jenny A. Westgate ◽  
Laura Bennet ◽  
Vincent Roelfsema ◽  
Harmen H. De Haan ◽  
...  
Keyword(s):  
Fetal Sheep ◽  
Profound Hypotension ◽  
Electrocardiographic Changes ◽  
Near Term

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.

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