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

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.

1990 ◽  
Vol 68 (2) ◽  
pp. 489-495 ◽  
Author(s):  
B. J. Koos ◽  
K. Matsuda

The possibility that adenosine mediates hypoxic inhibition of fetal breathing and eye movements was tested in nine chronically catheterized fetal sheep (0.8 term). Intracarotid infusion of adenosine (0.25 +/- 0.03 mg.min-1.kg-1) for 1 h to the fetus increased heart rate and hemoglobin concentration but did not significantly affect mean arterial pressure or blood gases. As with hypoxia, adenosine decreased the incidence of rapid eye movements by 55% and the incidence of breathing by 77% without significantly affecting the incidence of low-voltage electrocortical activity. However, with longer (9 h) administration, the incidence of breathing and eye movements returned to normal during the adenosine infusion. Intravenous infusion of theophylline, an adenosine receptor antagonist, prevented most of the reduction in the incidence of breathing and eye movements normally seen during severe hypoxia (delta arterial PO2 = -10 Torr). It is concluded that 1) adenosine likely depresses fetal breathing and eye movements during hypoxia and 2) downregulation of adenosine receptors may contribute to the adaptation of breathing and eye movements during prolonged hypoxia.


1986 ◽  
Vol 61 (3) ◽  
pp. 1071-1076 ◽  
Author(s):  
S. Ioffe ◽  
A. H. Jansen ◽  
V. Chernick

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.


2007 ◽  
Vol 293 (3) ◽  
pp. R1280-R1286 ◽  
Author(s):  
Laura Bennet ◽  
Lindsea C. Booth ◽  
Noha Ahmed-Nasef ◽  
Justin M. Dean ◽  
Joanne Davidson ◽  
...  

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.


2017 ◽  
Vol 89 (4) ◽  
pp. 249-261 ◽  
Author(s):  
Ryan K. Tisdale ◽  
Alexei L. Vyssotski ◽  
John A. Lesku ◽  
Niels C. Rattenborg

The functions of slow wave sleep (SWS) and rapid eye movement (REM) sleep, distinct sleep substates present in both mammals and birds, remain unresolved. One approach to gaining insight into their function is to trace the evolution of these states through examining sleep in as many taxonomic groups as possible. The mammalian and avian clades are each composed of two extant groups, i.e., the monotremes (echidna and platypus) and therian (marsupial and eutherian [or placental]) mammals, and Palaeognaths (cassowaries, emus, kiwi, ostriches, rheas, and tinamous) and Neognaths (all other birds) among birds. Previous electrophysiological studies of monotremes and ostriches have identified a unique “mixed” sleep state combining features of SWS and REM sleep unlike the well-delineated sleep states observed in all therian mammals and Neognath birds. In the platypus this state is characterized by periods of REM sleep-related myoclonic twitching, relaxed skeletal musculature, and rapid eye movements, occurring in conjunction with SWS-related slow waves in the forebrain electroencephalogram (EEG). A similar mixed state was also observed in ostriches; although in addition to occurring during periods with EEG slow waves, reduced muscle tone and rapid eye movements also occurred in conjunction with EEG activation, a pattern typical of REM sleep in Neognath birds. Collectively, these studies suggested that REM sleep occurring exclusively as an integrated state with forebrain activation might have evolved independently in the therian and Neognath lineages. To test this hypothesis, we examined sleep in the elegant crested tinamou (Eudromia elegans), a small Palaeognath bird that more closely resembles Neognath birds in size and their ability to fly. A 24-h period was scored for sleep state based on electrophysiology and behavior. Unlike ostriches, but like all of the Neognath birds examined, all indicators of REM sleep usually occurred in conjunction with forebrain activation in tinamous. The absence of a mixed REM sleep state in tinamous calls into question the idea that this state is primitive among Palaeognath birds and therefore birds in general.


1987 ◽  
Vol 62 (3) ◽  
pp. 1033-1039 ◽  
Author(s):  
B. J. Koos ◽  
H. Sameshima ◽  
G. G. Power

Graded isocapnic hypoxemia was produced in unanesthetized fetal sheep by varying the inspired O2 concentration (21, 12, 10.5, and 9%) of the ewe. This produced corresponding mean preductal arterial O2 tension (PaO2) values of 25.2 +/- 1.1 (control), 20.1 +/- 1.0 (mild hypoxia), 17.8 +/- 0.9 (moderate hypoxia), and 16.8 +/- 1.4 Torr (severe hypoxia). These were associated with mean arterial O2 contents (CaO2) of 7.18 +/- 0.44, 5.19 +/- 0.34, 4.24 +/- 0.33, and 3.27 +/- 0.20 ml/dl, respectively. The most severe hypoxia was associated with metabolic acidosis and fetal bradycardia. Hypoxia did not reduce significantly the incidence of low-voltage electrocortical activity. The incidence of breathing and rapid eye movements was not affected by mild hypoxia; however, the incidence of both was significantly reduced during moderate and severe hypoxia. It is concluded that 1) acute reductions in the mean PaO2 of 5.9 +/- 0.6 Torr and CaO2 of 2.00 +/- 0.23 ml/dl are critical in that greater reductions inhibit fetal eye and breathing activity and 2) hypoxia probably inhibits eye and breathing movements by altering sleep state.


1997 ◽  
Vol 272 (6) ◽  
pp. R1912-R1917 ◽  
Author(s):  
K. M. Moritz ◽  
K. Tangalakis ◽  
E. M. Wintour

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.


2001 ◽  
Vol 90 (1) ◽  
pp. 114-120 ◽  
Author(s):  
Sandrine H. Launois ◽  
Nathan Averill ◽  
Joseph H. Abraham ◽  
Debra A. Kirby ◽  
J. Woodrow Weiss

Spontaneous and provoked nonrespiratory arousals can be accompanied by a patterned hemodynamic response. To investigate whether a patterned response is also elicited by respiratory arousals, we compared nonrespiratory arousals (NRA) to respiratory arousals (RA) induced by airway occlusion during non-rapid eye movement sleep. We monitored mean arterial blood pressure (MAP), heart rate, iliac and renal blood flow, and sleep stage in 7 pigs during natural sleep. Iliac and renal vascular resistance were calculated. Airway occlusions were obtained by manually inflating a chronically implanted tracheal balloon during sleep. The balloon was quickly deflated as soon as electroencephalogram arousal occurred. As previously reported, NRA generally elicited iliac vasodilation, renal vasoconstriction, little change in MAP, and tachycardia. In contrast, RA generally elicited iliac and renal vasoconstriction, an increase in MAP and tachycardia. The frequent occurrence of iliac vasoconstriction and arterial pressure elevation following RA but not NRA suggests that sleep state change alone does not account for the hemodynamic response to airway occlusion during sleep.


1989 ◽  
Vol 256 (5) ◽  
pp. R1063-R1068
Author(s):  
M. Espinoza ◽  
R. Riquelme ◽  
A. M. Germain ◽  
J. Tevah ◽  
J. T. Parer ◽  
...  

Intravenous administration of the opioid receptor antagonist naloxone to asphyxiated fetal sheep increases the arterial blood pressure. We examined the hypothesis that endogenous opioids modify the cardiac output distribution during asphyxia due to changes in the vascular resistance of some fetal organs. Thirteen fetal sheep (0.8-0.9 of gestation) were chronically catheterized. Fetal asphyxia was induced by reducing the uterine blood flow with an inflatable occluder around the common internal iliac artery to approximately 50% of control for 40 min. Naloxone solution or the solvent alone was added for the last 20 min. Asphyxia caused hypertension, and the fetal arterial blood pressure further increased when asphyxiated fetuses received naloxone. Heart, brain, and adrenal blood flows increased due to the increase in blood pressure, with no changes in their vascular resistances. In contrast, kidney and carcass blood flows decreased, and their vascular resistances increased. We conclude that endogenous opioids inhibit the vasoconstriction of these vascular beds during fetal asphyxia.


2003 ◽  
Vol 284 (4) ◽  
pp. H1057-H1063 ◽  
Author(s):  
Sheng-Xing Ma ◽  
Qun Fang ◽  
Brian Morgan ◽  
Michael G. Ross ◽  
Conrad R. Chao

The purpose of this study was to examine cardiovascular responses to fourth cerebral ventricle (4V) administration of nitroglycerin (NTG) or an inhibitor of nitric oxide (NO) synthase (NOS) in the near-term ovine and to determine whether, during birth, neuronal NOS (nNOS) is induced in noradrenergic A1 neurons in the medial nucleus tractus solitarius (mNTS). In chronically instrumented fetal sheep, 4V injection of NTG (1.2 nmol), an NO donor, produced an arterial blood depressor and a moderate decrease in heart rate. Arterial blood pressure is increased by 4V administration of N G-nitro-l-arginine methyl ester (10 nmnol), an inhibitor of NOS, in fetuses. Sections of the medulla from fetuses and newborn lambs were examined by using immunolabeling with tyrosine hydroxylase (TH) antibody combined with NADPH diaphorase (NADPHd) histochemistry, a marker of nNOS activity. The NADPHd-positive cells and TH-positive cells containing NADPHd reactivity were significantly increased in the mNTS of newborns compared with the fetuses. The results suggest that during birth, there is upregulation of NADPHd/nNOS in the noradrenergic neurons of mNTS resulting in a centrally mediated reduction of fetal arterial blood pressure.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1358-1358 ◽  
Author(s):  
Reena Das ◽  
Chris Fisher ◽  
Jasbir Kaur ◽  
Ayyub Helena ◽  
Amita Trehan ◽  
...  

Abstract Background: Deletional a+-thalassemia comprising of -a3.7 and -a4.2 deletions is commonly encountered in the Indian sub-continent but HbH disease, resulting from the co-inheritance of a+-thalassemia trait and ao-thalassemia trait, is uncommon with just a few cases reported. Few recent reports on the molecular characterization of patients with HbH disease from India has been published which includes both deletional a-thalassemia and non-deletional a-thalassemia. This report highlights the clinical and molecular heterogeneity of HbH disease from north India. Materials and Methods: We encountered 34 patients with HbH disease in 28 families from north India over 15 years and performed the molecular analysis to determine the frequency of both deletional and non-deletional alpha gene defects. Patients as well as parents and affected siblings were also studied for automated complete blood cell counts, reticulocyte counts and HbH inclusions using 1% brilliant cresyl blue. Cation exchange HPLC (Bio-Rad Laboratories, Hercules, CA, USA) and hemoglobin electrophoresis at pH 8.6 were performed. Genomic DNA from peripheral blood leucocytes was extracted by the phenol-chloroform method. A multiplex Gap-PCR was carried out as an initial screen which tested for deletions a3.7, a4.2, aSEA, aMED and aSA. Southern Blot for alpha and zeta probes with Bam H1 digest was performed on 20 subjects. PCR followed by sequencing for both a1 and a2 genes were done. The a–GlobinXS MLPA kit (MRC Holland) with 35 probes was used to screen for the extent of deletions. Results: Homozygous Hb Sallanches (a2 codon 104 G>A; Cys →Tyr) in 6 cases in 5 families was found. Homozygous polyadenylation signal mutation of a2(-AA) AATAAA →AATA—was detected in 3 cases. One patient each showed double heterozygosity for -a3.7/aHb Sallanches a, a76 +Ta/aHb Sallanches a. PolyAa/ aHb Sun Prairie a, aPolyAa/ a76 +Ta, and -a3.7/aHb Seal Rocka and aSeal Rock a/--. Three patients were double heterozygous for -a3.7/--SA. Fifteen patients from 12 families had a0 deletion of varying lengths in combination with -a3.7 based on the MLPA analysis. The extent of deletions was variable ranging from a0 starts upstream of z gene & extends downstream of a1, deletion of probes 1-18, deletion of probes 1-22 and deletion of probes 8-18.The genotype phenotype correlation illustrating the clinical heterogeneity of HbH disease is detailed in Table 1. Discussion: This is the largest series of cases of HbH disease encountered in Indians. Since HbH disease is uncommon in India, the clinical recognition of the diagnosis is limited to few centres and molecular characterization is incomplete. Our study shows considerable heterogeneity both at the molecular level as well as the clinical presentation. Alpha2 gene sequencing revealed a novel mutation with addition of +T at codon 76 leading to a frameshift mutation .MLPA will be useful in characterizing the approximate location of the breakpoints and designing simple GAP PCR assays to identify the deletion. Increased awareness amongst the clinicians as well as more diagnostic laboratories will help to identify more patients with HbH disease. Table 1: Genotype and phenotype correlation of cases with HbH Number of cases Clinical Severity Homozygous Hb Sallanches 6 cases (5 families) Severe anemia with early presentation Homozygous aPolyAa/ aPolyAa 3 cases Moderate anemia with presentation in the second decade Double heterozygous -a3.7/aHb Sallanches a 1 case Moderate anemia Double heterozygous a76 +Ta/aHb Sallanches a 1 case Moderate anemia with presentation in the third decade Double heterozygous aPolyAa/ aHb Sun Prairie a 1 case Moderate anemia with early presentation Double heterozygous aPolyAa/ a76 +Ta 1 case Moderate anemia with early presentation Homozygous a2 Codon 19 (-G) 1 case Severe anemia with early presentation Double heterozygous for -a3.7/--SA 3 cases Moderate anemia with presentation in the third decade Double heterozygous for aSeal Rock a/-- 1 case Severe anemia with early presentation Double heterozygous for -a3.7/aSeal Rock a 1 case Mild presentation at family screening in forth decade with mild anemia Double heterozygosity for -a3.7/-- 15 cases (13 families) Larger deletions showed early presentation with severe anemia and shorter deletions showed mild anemia Disclosures No relevant conflicts of interest to declare.


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