Altered fetal cardiovascular responses to  prolonged hypoxia after sinoaortic denervation

This study examines the role of the peripheral chemoreceptors in mediating fetal cardiovascular responses to prolonged hypoxia secondary to reduced uterine blood flow (RUBF). Fetal sheep were chronically instrumented for continuous heart rate (FHR), blood pressure (FBP), and carotid blood flow (CBF) measurements after bilateral sectioning of the carotid sinus and vagus nerves (denervated, n = 7) or sham denervation (intact, n = 7). Four days postoperatively, uterine blood flow was mechanically restricted, reducing fetal arterial oxygen saturation by 47.3% ( P < 0.01). An initial bradycardia was observed in intact (184.0 ± 10.7 to 160.5 ± 10.7 beats/min, not significant) but not denervated fetuses, followed by a tachycardia (180.0 ± 2.2 to 193.7 ± 2.7 beats/min, P < 0.05). FHR increased in denervated fetuses (175.5 ± 8.7 to 203.0 ± 17.9 beats/min, P < 0.05). FBP increased transiently in intact fetuses from 45.1 ± 1.0 to 55.4 ± 3.0 mmHg at 2 h ( P < 0.01), whereas denervated fetuses demonstrated a decrease in FBP from 47.1 ± 4.2 to 37.2 ± 3.7 mmHg (not significant). CBF increased ( P < 0.05) in both intact and denervated fetuses from 39.3 ± 2.8 and 29.7 ± 3.8 ml ⋅ min−1 ⋅ kg−1to 47.7 ± 0.4 and 39.1 ± 0.3 ml ⋅ min−1 ⋅ kg−1, respectively, whereas carotid vascular resistance decreased only in denervated fetuses (1.7 ± 0.1 to 1.1 ± 0.02 mmHg ⋅ ml−1 ⋅ min ⋅ kg−1, P < 0.05). We conclude that the peripheral chemoreceptors play an important role in mediating fetal cardiovascular responses to prolonged RUBF.

Download Full-text

Fetal endocrine responses to prolonged reduced uterine blood flow are altered following bilateral sectioning of the carotid sinus and vagus nerves

Journal of Endocrinology ◽

10.1677/joe.0.1570149 ◽

1998 ◽

Vol 157 (1) ◽

pp. 149-155 ◽

Cited By ~ 6

Author(s):

PE Stein ◽

SE White ◽

J Homan ◽

L Fraher ◽

HH McGarrigle ◽

...

Keyword(s):

Blood Flow ◽

Angiotensin Ii ◽

Carotid Sinus ◽

Arterial Oxygen Saturation ◽

Cardiovascular Responses ◽

Arterial Oxygen ◽

Uterine Blood Flow ◽

Vagus Nerves ◽

Fetal Sheep ◽

Fetal Plasma

The present study examines the effect of carotid sinus/vagosympathetic denervation on fetal endocrine responses to prolonged reduced uterine blood flow (RUBF). Fetal sheep had vascular catheters inserted following bilateral sectioning of the carotid sinus and vagus nerves (denervated, n = 7) or sham denervation (intact, n = 7). Uterine blood flow was mechanically restricted at 126.1 +/- 0.7 days (mean +/- S.E.M.) for 24 h, decreasing arterial oxygen saturation by 47.3 +/- 2.6% (P < 0.01). Fetal plasma samples were obtained at -1, 3, 6, 12 and 24 h for subsequent analyses of arginine vasopressin (AVP), angiotensin II and catecholamines. The AVP response to prolonged RUBF was markedly attenuated in denervated fetuses (15.6 +/- 3.6 to 34.9 +/- 6.0 pg/ml) when compared with intact (10.0 +/- 1.4 to 127.3 +/- 28.4 pg/ml). In contrast, intact fetuses demonstrated no change in plasma angiotensin II concentrations with RUBF whereas denervated fetuses demonstrated a marked increase from 47.5 +/- 18.9 to 128.7 +/- 34.2 pg/ml. The norepinephrine and epinephrine responses to prolonged RUBF were attenuated in denervated fetuses (950.1 +/- 308.9 and 155.8 +/- 58.5 to 1268.3 +/- 474.6 and 290.6 +/- 160.2 pg/ml respectively) when compared with intact (1558.3 +/- 384.4 and 547.3 +/- 304.7 pg/ml to 3289.2 +/- 1219.8 and 896.8 +/- 467.8 pg/ml respectively). These results support a role for the peripheral chemoreceptors in mediating fetal endocrine responses to prolonged RUBF, which may in part lead to the altered cardiovascular responses observed in denervated fetuses under these conditions.

Download Full-text

Role of hypoxemia for the cardiovascular responses to apnea during exercise

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00036.2002 ◽

2002 ◽

Vol 283 (5) ◽

pp. R1227-R1235 ◽

Cited By ~ 22

Author(s):

Peter Lindholm ◽

Jessica Nordh ◽

Dag Linnarsson

Keyword(s):

Impedance Cardiography ◽

Arterial Oxygen Saturation ◽

Peripheral Resistance ◽

Cardiovascular Responses ◽

Arterial Oxygen ◽

Interindividual Differences ◽

Arterial Blood ◽

Oxygen Oxygen ◽

Highly Correlated

We sought to define the role of hypoxemia in eliciting the cardiovascular responses to apnea during exercise. Eleven men performed repeated apneas during 100-W steady-state exercise, either with normoxic gas (air) or 95% oxygen (oxygen). Beat-by-beat arterial blood pressure, arterial oxygen saturation, and heart rate (HR) were determined, and stroke volume (SV) was estimated from impedance cardiography calibrated with soluble gas rebreathing. There were large interindividual variabilities of HR, mean arterial pressure (MAP), and total peripheral resistance (TPR) at end-apnea (ea). However, for each individual, HRea, MAPea, and TPRea were highly correlated between air and oxygen ( R = 0.94, 0.78, and 0.93). HR decreased and MAP increased faster during apnea with air than with oxygen (ANOVA, P < 0.05), but MAPea was not different between conditions. Cardiac output was reduced by 33% with air and by 11% with oxygen ( P < 0.001 for air vs. oxygen). We conclude that the hypoxemia component cannot account for the wide interindividual differences of HR and TPR responses to apnea. However, hypoxemia augments the HR and TPR responses and may limit the MAP response to apnea by preventing a bradycardia-associated increase of SV.

Download Full-text

Role of peripheral and central chemoreceptors in the initiation of fetal respiration

Journal of Applied Physiology ◽

10.1152/jappl.1975.38.3.407 ◽

1975 ◽

Vol 38 (3) ◽

pp. 407-410 ◽

Cited By ~ 7

Author(s):

V. Chernick ◽

E. E. Faridy ◽

R. D. Pagtakhan

Keyword(s):

Carotid Sinus ◽

Blood Gases ◽

Fetal Sheep ◽

Peripheral Chemoreceptors ◽

Central Chemoreceptors ◽

Bilateral Carotid ◽

Fetal Respiration ◽

A Minor ◽

The Relationship

The relationship between fetal femoral arterial P02 and PC02 was evalulated in 13 fetal sheep with intact and denervated peripheral chemoreceptors. With intact chemoreceptors, a significant relationship was found between fetal Pa02 and PaC02 at the time of the first breath (Pa02 = 2.57 + 0.09 PaC02; r = 0.62, P less than 0.05)mfollowing bilateral carotid sinus nerve section (CSN) or total peripheral chemodenervation (TD), PaC02. Comparison of the intact, CSN, and TD blood gases at the time of the first breath demonstrated that a) severe hypoxemia stimulates fetal respiration even following total peripheral chemodenervation; b) fetal central chemoreceptors do not respond to PaC02; c) PaC02 acting via peripheral chemoreceptors has a minor modulating effect on the degree of hypoxemia required to initiate fetal respiration. At a PaC02 below 40 mmHg this effect is inhibitory, acting via the carotid body. At a PaC02 above 90 mmHg this effect is stimulatory, acting via both carotid and aortic bodies.

Download Full-text

Effects of prostaglandins on fetal breathing do not involve peripheral chemoreceptors

Journal of Applied Physiology ◽

10.1152/jappl.1987.62.1.271 ◽

1987 ◽

Vol 62 (1) ◽

pp. 271-277 ◽

Cited By ~ 16

Author(s):

D. T. Murai ◽

L. D. Wallen ◽

C. C. Lee ◽

R. I. Clyman ◽

F. Mauray ◽

...

Keyword(s):

Carotid Sinus ◽

Vagus Nerves ◽

Fetal Sheep ◽

Peripheral Chemoreceptors ◽

Respective Control ◽

Fetal Breathing ◽

Fetal Breathing Movements ◽

Site Of Action ◽

Pg E2 ◽

Stimulation Of

In sheep, prostaglandin (PG) E2 inhibits fetal breathing movements and meclofenamate, a PG synthetase inhibitor, causes a marked stimulation of fetal breathing movements; the site of action of these agents is not known. To determine whether these effects are mediated through the peripheral chemoreceptors, we studied 13 fetal sheep at gestational ages of 127 to 138 days. Seven fetuses had bilateral section of the carotid sinus and vagus nerves (denervated); six had sham operations. Beginning at least 6 days after the operation, we infused PGE2 (0.6 microgram X kg-1 X min-1) into five denervated and five sham-operated fetuses and meclofenamate (0.4 mg X kg-1 X h-1) into six denervated and four sham-operated fetuses. Infusions averaged 20 h in duration. During preinfusion control periods, the incidence of fetal breathing movements (% of time) was lower in denervated than in sham-operated fetuses (18.9% vs. 31.5%; P less than 0.005). In both groups, the incidence of fetal breathing movements was decreased by PGE2 and was increased by meclofenamate; when expressed as absolute values, the magnitude of the changes with both agents was greater in sham-operated fetuses than denervated fetuses. However, the effects were similar in both groups when the changes were expressed as a percent of the respective control values. The incidence of fetal breathing movements (% of control) was decreased by PGE2 to 25.4% in denervated and to 28.2% in sham-operated fetuses and was increased by meclofenamate to 297.3% in denervated and to 304.0% in sham-operated fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

Effects of restricting uteroplacental blood flow on concentrations of corticotrophin-releasing hormone, adrenocorticotrophin, cortisol, and prostaglandin E2 in the sheep fetus during late pregnancy

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y92-196 ◽

1992 ◽

Vol 70 (10) ◽

pp. 1396-1402 ◽

Cited By ~ 23

Author(s):

Alicia Sue-Tang ◽

Alan D. Booking ◽

A. Nigel Brooks ◽

Stuart Hooper ◽

Susan E. White ◽

...

Keyword(s):

Blood Flow ◽

Umbilical Vein ◽

Arterial Oxygen Saturation ◽

Control Level ◽

Arterial Oxygen ◽

Prostaglandin E ◽

Uterine Blood Flow ◽

Concentration Difference ◽

Releasing Hormone ◽

Fetal Plasma

We have examined the effects of reduced uterine blood flow and prolonged fetal hypoxemia on the temporal relationship between changes in hormones associated with the activity of the pituitary–adrenal axis (corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), cortisol, and prostaglandin E2 (PGE2)) in the ovine fetus at 120–125 days of pregnancy, and we sought evidence for placental secretion of CRH and ACTH during prolonged hypoxemia. Uterine blood flow was reduced by placing an adjustable Teflon clamp around the maternal common internal iliac artery to decrease fetal arterial oxygen saturation from mean values of 59.1 ± 3.3 to 25.7 ± 4.6% (±SEM, n = 10). There was a transient peak in immunoreactive (IR-) CRH at 1–2 h after reducing uterine blood flow. IR-ACTH rose to peak values at +2 h, then gradually decreased to control level by +12 h. Fetal plasma cortisol and PGE2 concentrations were elevated significantly by +2 and +4 h, respectively, and at 20–24 h. The identity of IR-CRH in fetal plasma and in ovine placental extracts was confirmed by HPLC, but there was no consistent umbilical vein – femoral arterial concentration difference for either IR-CRH or IR-ACTH during normoxemia or hypoxemia. We conclude that a sequence of endocrine changes involving CRH, ACTH, PGE2, and cortisol occurs in the fetus during a prolonged reduction in uterine blood flow. However, we did not obtain evidence, for placental secretion of either CRH or ACTH in response to this manipulation.Key words: fetus, adrenocorticotrophin, corticotrophin-releasing hormone, prostaglandin E2, placenta.

Download Full-text

Fetal endocrine responses to prolonged hypoxemia in sheep

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.259.4.r703 ◽

1990 ◽

Vol 259 (4) ◽

pp. R703-R708 ◽

Cited By ~ 5

Author(s):

S. B. Hooper ◽

C. L. Coulter ◽

J. M. Deayton ◽

R. Harding ◽

G. D. Thorburn

Keyword(s):

Blood Flow ◽

Time Course ◽

Arterial Oxygen Saturation ◽

Arterial Oxygen ◽

Plasma Norepinephrine ◽

Uterine Blood Flow ◽

Fetal Plasma ◽

Arterial Ph ◽

Fetal Breathing ◽

Fetal Breathing Movements

Our aim was to characterize the pattern of release of epinephrine, norepinephrine, arginine vasopressin (AVP), cortisol (hydrocortisone), and prostaglandin E2 (PGE2) into the fetal circulation during prolonged reductions in uterine blood flow (RUBF). In five sheep RUBF was induced for 24 h, whereas in another five sheep (controls) uterine blood flow was not reduced. Fetal arterial oxygen saturation was decreased from 60.5 +/- 3.6 to 20.3 +/- 1.6% after 2 h of RUBF and remained significantly reduced for the entire RUBF period. The incidence of fetal breathing movements (FBM) and fetal arterial pH were reduced from 36.7 +/- 4.5 min/h and 7.36 +/- 0.01 to 4.3 +/- 1.8 min/h and 7.13 +/- 0.02, respectively, after 2 h of RUBF, but both had returned to control levels after 14 h. Fetal plasma AVP and epinephrine concentrations were increased from 4.4 +/- 0.5 pg/ml and 0.19 +/- 0.05 ng/ml to 333.8 +/- 41.5 pg/ml and 1.5 +/- 0.6 ng/ml, respectively, after 2 h and then declined to near control levels after 12 h of RUBF. Fetal plasma norepinephrine and cortisol concentrations were increased from 1.3 +/- 0.4 and 4.0 +/- 2.2 ng/ml to 6.1 +/- 1.8 and 13.5 +/- 4.1 ng/ml, respectively, after 2 h of RUBF, and both remained significantly elevated throughout the remainder of the RUBF period. Fetal plasma PGE2 concentrations progressively increased (from 1.9 +/- 0.4 to 8.8 +/- 1.7 nmol/l at 12 h) as the duration of RUBF increased and were still significantly elevated after 24 h. The time course for the increase in PGE2 during RUBF was very similar to the increases in arterial pH and in the incidence of FBM.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

Cardiovascular adjustments to acute hypoxemia superimposed on chronic hypoxemia in lambs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.3.h974 ◽

1995 ◽

Vol 268 (3) ◽

pp. H974-H979

Author(s):

M. Dalinghaus ◽

J. W. Gratama ◽

W. G. Zijlstra ◽

J. R. Kuipers

Keyword(s):

Blood Flow ◽

Oxygen Saturation ◽

Oxygen Supply ◽

Pulmonary Stenosis ◽

Arterial Oxygen Saturation ◽

Cardiovascular Responses ◽

Arterial Oxygen ◽

Blood Flows ◽

Regional Blood Flows ◽

Chronic Hypoxemia

Cardiovascular responses to acute hypoxemia are in part mediated through adrenergic and chemoreceptor stimulation. In chronic hypoxemia the response to these stimuli may be blunted. Therefore, we determined whether the cardiovascular responses to acute hypoxemia superimposed on 3–4 wk of chronic hypoxemia were blunted in lambs with an experimental cardiac right-to-left shunt (combination of atrial septal defect and variable pulmonary stenosis). Cardiovascular variables and regional blood flows were determined during chronic hypoxemia and after acutely reducing the arterial oxygen saturation by increasing the cardiac right-to-left shunt. Arterial oxygen saturation decreased (65 +/- 7 to 40 +/- 7%, P < 0.001) and systemic blood flow increased (164 +/- 63 to 233 +/- 100 ml.min-1.kg-1, P < 0.01), maintaining systemic oxygen supply and oxygen uptake. Blood flow to the myocardium (P < 0.01), the adrenals (P < 0.05), and the brain (0.05 < P < 0.10) increased, and oxygen supply to these organs was maintained. Conversely, blood flow to the kidneys and the gastrointestinal tract was unaltered, so that oxygen supply to these organs was decreased. The responses to acute hypoxemia in chronically hypoxemic lambs were similar to those previously reported in normoxemic lambs. We conclude that the cardiovascular responses to acute hypoxemia in chronically hypoxemic lambs are not blunted.

Download Full-text

Behavioral activity during prolonged hypoxemia in fetal sheep

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.6.2420 ◽

1988 ◽

Vol 65 (6) ◽

pp. 2420-2426 ◽

Cited By ~ 49

Author(s):

A. D. Bocking ◽

R. Gagnon ◽

K. M. Milne ◽

S. E. White

Keyword(s):

Blood Flow ◽

Eye Movements ◽

Normal Incidence ◽

Behavioral Activity ◽

Uterine Blood Flow ◽

Fetal Sheep ◽

Pregnant Sheep ◽

Fetal Breathing ◽

Fetal Breathing Movements ◽

Internal Iliac

Experiments were conducted in unanesthetized, chronically catheterized pregnant sheep to determine the fetal behavioral response to prolonged hypoxemia produced by restricting uterine blood flow. Uterine blood flow was reduced by adjusting a vascular occluder placed around the maternal common internal iliac artery to decrease fetal arterial O2 content from 6.1 +/- 0.3 to 4.1 +/- 0.3 ml/dl for 48 h. Associated with the decrease in fetal O2 content, there was a slight increase in fetal arterial PCO2 and decrease in pH, which were both transient. There was an initial inhibition of both fetal breathing movements and eye movements but no change in the pattern of electrocortical activity. After this initial inhibition there was a return to normal incidence of both fetal breathing movements and eye movements by 16 h of the prolonged hypoxemia. These studies indicate that the chronically catheterized sheep fetus is able to adapt behaviorally to a prolonged decrease in arterial O2 content secondary to the restriction of uterine blood flow.

Download Full-text