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. 1985 Nov;368:109–129. doi: 10.1113/jphysiol.1985.sp015849

Metabolic and cardiovascular effects on fetal sheep of sustained reduction of uterine blood flow.

W Gu, C T Jones, J T Parer
PMCID: PMC1192588  PMID: 4078738

Abstract

The effects on the fetus and placenta of graded reductions of uterine blood flow to 30-90% of control have been studied in sheep at days 125-143 of pregnancy. Reduction of uterine flow to 70-90% of control had little effect upon fetal oxygenation or heart rate or blood pressure but elevated fetal plasma catecholamine concentration. Reduction of flow to 30-50% of control depressed fetal arterial and umbilical venous PO2 but had little effect upon oxygen consumption unless the umbilical venous value fell below about 14 mmHg when it was depressed by up to 30%. Placental oxygen consumption did not fall and was therefore maintained at the expense of the fetus. Fetal arterial pressure rose by 10-12 mmHg and heart rate fell by about 30 beats/min during the first 10-15 min then rose above its initial value. Plasma adrenaline and noradrenaline concentrations rose progressively at a rate which increased with greater degrees of asphyxia. When uterine blood flow was reduced below one-half of normal, net placental consumption of glucose fell and there was evidence of substantial provision of glucose and lactate from the fetus. Fetal production of lactate increased sharply and much of this appeared to be consumed by the placenta at a rate sufficient to account entirely for the deficit in net glucose consumption. The results are consistent with the hypothesis that the fetus senses even small changes in uterine blood flow that are alone insufficient to elicit significant blood gas changes. When the fall in uterine flow caused by arterial compression is relatively large, nutrient supply to the placenta is maintained at the expense of the fetus and as a result of fetal glucose and lactate production. The elevation of fetal arterial PCO2 appears to enhance fetal responses to hypoxia. The results are discussed in relation to the fetal responses to brief and prolonged reductions in uterine blood flow.

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Selected References

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  1. ASSALI N. S., DASGUPTA K., KOLIN A., HOLMS L. Measurement of uterine blood flow and uterine metabolism. V. Changes during spontaneous and induced labor in unanesthetized pregnant sheep and dogs. Am J Physiol. 1958 Dec;195(3):614–620. doi: 10.1152/ajplegacy.1958.195.3.614. [DOI] [PubMed] [Google Scholar]
  2. Anand R. S., Sperling M. A., Ganguli S., Nathanielsz P. W. Bidirectional placental transfer of glucose and its turnover in fetal and maternal sheep. Pediatr Res. 1979 Jun;13(6):783–787. doi: 10.1203/00006450-197906000-00014. [DOI] [PubMed] [Google Scholar]
  3. Boddy K., Dawes G. S., Fisher R., Pinter S., Robinson J. S. Foetal respiratory movements, electrocortical and cardiovascular responses to hypoxaemia and hypercapnia in sheep. J Physiol. 1974 Dec;243(3):599–618. doi: 10.1113/jphysiol.1974.sp010768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bristow J., Rudolph A. M., Itskovitz J., Barnes R. Hepatic oxygen and glucose metabolism in the fetal lamb. Response to hypoxia. J Clin Invest. 1983 May;71(5):1047–1061. doi: 10.1172/JCI110855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. COMLINE R. S., SILVER I. A., SILVER M. FACTORS RESPONSIBLE FOR THE STIMULATION OF THE ADRENAL MEDULLA DURING ASPHYXIA IN THE FOETAL LAMB. J Physiol. 1965 May;178:211–238. doi: 10.1113/jphysiol.1965.sp007624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. COMLINE R. S., SILVER M. The release of adrenaline and noradrenaline from the adrenal glands of the foetal sheep. J Physiol. 1961 May;156:424–444. doi: 10.1113/jphysiol.1961.sp006685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chapman R. L., Dawes G. S., Rurak D. W., Wilds P. L. Breathing movements in fetal lambs and the effect of hypercapnia. J Physiol. 1980 May;302:19–29. doi: 10.1113/jphysiol.1980.sp013227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clapp J. F., 3rd Effect of epinephrine infusion on maternal and uterine oxygen uptake in the pregnant ewe. Am J Obstet Gynecol. 1979 Jan 15;133(2):208–212. doi: 10.1016/0002-9378(79)90478-2. [DOI] [PubMed] [Google Scholar]
  9. Clapp J. F., 3rd, McLaughlin M. K., Larrow R., Farnham J., Mann L. I. The uterine hemodynamic response to repetitive unilateral vascular embolization in the pregnant ewe. Am J Obstet Gynecol. 1982 Oct 1;144(3):309–318. doi: 10.1016/0002-9378(82)90584-1. [DOI] [PubMed] [Google Scholar]
  10. Clapp J. F., 3rd The relationship between blood flow and oxygen uptake in the uterine and umbilical circulations. Am J Obstet Gynecol. 1978 Oct 15;132(4):410–413. doi: 10.1016/0002-9378(78)90776-7. [DOI] [PubMed] [Google Scholar]
  11. Cohen W. R., Piasecki G. J., Jackson B. T. Plasma catecholamines during hypoxemia in fetal lamb. Am J Physiol. 1982 Nov;243(5):R520–R525. doi: 10.1152/ajpregu.1982.243.5.R520. [DOI] [PubMed] [Google Scholar]
  12. Cohn H. E., Sacks E. J., Heymann M. A., Rudolph A. M. Cardiovascular responses to hypoxemia and acidemia in fetal lambs. Am J Obstet Gynecol. 1974 Nov 15;120(6):817–824. doi: 10.1016/0002-9378(74)90587-0. [DOI] [PubMed] [Google Scholar]
  13. Dawes G. S., Fox H. E., Leduc B. M., Liggins G. C., Richards R. T. Respiratory movements and rapid eye movement sleep in the foetal lamb. J Physiol. 1972 Jan;220(1):119–143. doi: 10.1113/jphysiol.1972.sp009698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Engel P. C., Jones J. B. Causes and elimination of erratic blanks in enzymatic metabolite assays involving the use of NAD+ in alkaline hydrazine buffers: improved conditions for the assay of L-glutamate, L-lactate, and other metabolites. Anal Biochem. 1978 Aug 1;88(2):475–484. doi: 10.1016/0003-2697(78)90447-5. [DOI] [PubMed] [Google Scholar]
  15. Gilbert M., Leturque A. Fetal weight and its relationship to placental blood flow and placental weight in experimental intrauterine growth retardation in the rat. J Dev Physiol. 1982 Aug;4(4):237–246. [PubMed] [Google Scholar]
  16. HUGGETT A. S., NIXON D. A. Use of glucose oxidase, peroxidase, and O-dianisidine in determination of blood and urinary glucose. Lancet. 1957 Aug 24;273(6991):368–370. doi: 10.1016/s0140-6736(57)92595-3. [DOI] [PubMed] [Google Scholar]
  17. Harding R., Poore E. R., Cohen G. L. The effect of brief episodes of diminished uterine blood flow on breathing movements, sleep states and heart rate in fetal sheep. J Dev Physiol. 1981 Aug;3(4):231–243. [PubMed] [Google Scholar]
  18. Harding R., Sigger J. N., Wickham P. J. Fetal and maternal influences on arterial oxygen levels in the sheep fetus. J Dev Physiol. 1983 Aug;5(4):267–276. [PubMed] [Google Scholar]
  19. Hay W. W., Jr, Sparks J. W., Quissell B. J., Battaglia F. C., Meschia G. Simultaneous measurements of umbilical uptake, fetal utilization rate, and fetal turnover rate of glucose. Am J Physiol. 1981 Jun;240(6):E662–E668. doi: 10.1152/ajpendo.1981.240.6.E662. [DOI] [PubMed] [Google Scholar]
  20. Hill D. E., Myers R. E., Holt A. B., Scott R. E., Cheek D. B. Fetal growth retardation produced by experimental placental insufficiency in the rhesus monkey. II. Chemical composition of the brain, liver, muscle and carcass. Biol Neonate. 1971;19(1):68–82. doi: 10.1159/000240403. [DOI] [PubMed] [Google Scholar]
  21. Itskovitz J., Goetzman B. W., Rudolph A. M. The mechanism of late deceleration of the heart rate and its relationship to oxygenation in normoxemic and chronically hypoxemic fetal lambs. Am J Obstet Gynecol. 1982 Jan 1;142(1):66–73. doi: 10.1016/s0002-9378(16)32286-4. [DOI] [PubMed] [Google Scholar]
  22. Jansen C. A., Krane E. J., Thomas A. L., Beck N. F., Lowe K. C., Joyce P., Parr M., Nathanielsz P. W. Continuous variability of fetal PO2 in the chronically catheterized fetal sheep. Am J Obstet Gynecol. 1979 Aug 1;134(7):776–783. doi: 10.1016/0002-9378(79)90947-5. [DOI] [PubMed] [Google Scholar]
  23. Jensen A., Künzel W. The difference between fetal transcutaneous pO2 and arterial pO2 during labour. Gynecol Obstet Invest. 1980;11(5):249–264. doi: 10.1159/000299845. [DOI] [PubMed] [Google Scholar]
  24. Jones C. T., Parer J. T. The effect of alterations in placental blood flow on the growth of and nutrient supply to the fetal guinea-pig. J Physiol. 1983 Oct;343:525–537. doi: 10.1113/jphysiol.1983.sp014907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jones C. T., Ritchie J. W. The cardiovascular effects of circulating catecholamines in fetal sheep. J Physiol. 1978 Dec;285:381–393. doi: 10.1113/jphysiol.1978.sp012577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jones C. T., Ritchie J. W., Walker D. The effects of hypoxia on glucose turnover in the fetal sheep. J Dev Physiol. 1983 Aug;5(4):223–235. [PubMed] [Google Scholar]
  27. Jones C. T., Robinson R. O. Plasma catecholamines in foetal and adult sheep. J Physiol. 1975 Jun;248(1):15–33. doi: 10.1113/jphysiol.1975.sp010960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Keller R., Oke A., Mefford I., Adams R. N. Liquid chromatographic analysis of catecholamines routine assay for regional brain mapping. Life Sci. 1976 Oct 1;19(7):995–1003. doi: 10.1016/0024-3205(76)90290-3. [DOI] [PubMed] [Google Scholar]
  29. Künzel W., Kastendieck E., Hohmann M. Heart rate and blood pressure response and metabolic changes in the sheep fetus following reduction of uterine blood flow. Gynecol Obstet Invest. 1983;15(5):300–317. doi: 10.1159/000299425. [DOI] [PubMed] [Google Scholar]
  30. MENDELSOHN D., LEVIN N. W. A colorimetric micromethod for the estimation of antipyrine in plasma or serum. S Afr J Med Sci. 1960 Apr;25:13–18. [PubMed] [Google Scholar]
  31. Meschia G., Battaglia F. C., Hay W. W., Sparks J. W. Utilization of substrates by the ovine placenta in vivo. Fed Proc. 1980 Feb;39(2):245–249. [PubMed] [Google Scholar]
  32. Morriss F. H., Jr, Rosenfeld C. R., Resnik R., Meschia G., Makowski E. L., Battaglia F. C. Growth of uterine oxygen and glucose uptakes during pregnancy in sheep. Gynecol Invest. 1974;5(4):230–241. doi: 10.1159/000301654. [DOI] [PubMed] [Google Scholar]
  33. Parer J. T., Krueger T. R., Harris J. L. Fetal oxygen consumption and mechanisms of heart rate response during artificially produced late decelerations of fetal heart rate in sheep. Am J Obstet Gynecol. 1980 Feb 15;136(4):478–482. doi: 10.1016/0002-9378(80)90674-2. [DOI] [PubMed] [Google Scholar]
  34. Peeters L. L., Sheldon R. E., Jones M. D., Jr, Makowski E. L., Meschia G. Blood flow to fetal organs as a function of arterial oxygen content. Am J Obstet Gynecol. 1979 Nov 1;135(5):637–646. doi: 10.1016/s0002-9378(16)32989-1. [DOI] [PubMed] [Google Scholar]
  35. Ramsey E. M. Uteroplacental circulation during labor. Clin Obstet Gynecol. 1968 Mar;11(1):78–95. doi: 10.1097/00003081-196803000-00005. [DOI] [PubMed] [Google Scholar]
  36. Robinson J. S., Jones C. T., Thorburn G. D. The effects of hypoxaemia in fetal sheep. J Clin Pathol Suppl (R Coll Pathol) 1977;11:127–133. doi: 10.1136/jcp.s3-11.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rosenfeld C. R., Morriss F. H., Jr, Makowski E. L., Meschia G., Battaglia F. C. Circulatory changes in the reproductive tissues of ewes during pregnancy. Gynecol Invest. 1974;5(5-6):252–268. doi: 10.1159/000301658. [DOI] [PubMed] [Google Scholar]
  38. Rudolph A. M., Heymann M. A. Validation of the antipyrine method for measuring fetal umbilical blood flow. Circ Res. 1967 Aug;21(2):185–190. doi: 10.1161/01.res.21.2.185. [DOI] [PubMed] [Google Scholar]
  39. Rudolph A. M. The fetal circulation and its response to stress. J Dev Physiol. 1984 Feb;6(1):11–19. [PubMed] [Google Scholar]
  40. Rurak D. W., Gruber N. C. Increased oxygen consumption associated with breathing activity in fetal lambs. J Appl Physiol Respir Environ Exerc Physiol. 1983 Mar;54(3):701–707. doi: 10.1152/jappl.1983.54.3.701. [DOI] [PubMed] [Google Scholar]
  41. Rurak D. W., Gruber N. C. The effect of neuromuscular blockade on oxygen consumption and blood gases in the fetal lamb. Am J Obstet Gynecol. 1983 Jan 15;145(2):258–262. doi: 10.1016/0002-9378(83)90502-1. [DOI] [PubMed] [Google Scholar]
  42. Simmons M. A., Battaglia F. C., Meschia G. Placental transfer of glucose. J Dev Physiol. 1979 Jun;1(3):227–243. [PubMed] [Google Scholar]
  43. WIGGLESWORTH J. S. EXPERIMENTAL GROWTH RETARDATION IN THE FOETAL RAT. J Pathol Bacteriol. 1964 Jul;88:1–13. [PubMed] [Google Scholar]
  44. WRIGHT H. P., MORRIS N., OSBORN S. B., HART A. Effective uterine blood flow during labor. Am J Obstet Gynecol. 1958 Jan;75(1):3–10. doi: 10.1016/0002-9378(58)90542-8. [DOI] [PubMed] [Google Scholar]
  45. Wilkening R. B., Anderson S., Martensson L., Meschia G. Placental transfer as a function of uterine blood flow. Am J Physiol. 1982 Mar;242(3):H429–H436. doi: 10.1152/ajpheart.1982.242.3.H429. [DOI] [PubMed] [Google Scholar]
  46. Wilkening R. B., Meschia G. Fetal oxygen uptake, oxygenation, and acid-base balance as a function of uterine blood flow. Am J Physiol. 1983 Jun;244(6):H749–H755. doi: 10.1152/ajpheart.1983.244.6.H749. [DOI] [PubMed] [Google Scholar]
  47. Yaffe H., Katz M., Parer J. T. Technique for stepwise reduction of uterine blood flow in the chronically prepared pregnant sheep. Gynecol Obstet Invest. 1982;13(4):257–260. doi: 10.1159/000299527. [DOI] [PubMed] [Google Scholar]

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