Display options
Share it on

J Physiol. 2005 Jan 15;562:493-505. doi: 10.1113/jphysiol.2004.074161. Epub 2004 Oct 28.

Effects of gestational age and cortisol treatment on ovine fetal heart function in a novel biventricular Langendorff preparation.

The Journal of physiology

Andrew J W Fletcher, Alison J Forhead, Abigail L Fowden, Will R Ford, Peter W Nathanielsz, Dino A Giussani

Affiliations

  1. Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.

PMID: 15513943 PMCID: PMC1665501 DOI: 10.1113/jphysiol.2004.074161

Abstract

Structural and functional maturation of a number of fetal organs and physiological systems occurs in the immediate period prior to term, in association with the prepartum increase in fetal plasma cortisol concentration. At present, little is known about how myocardial sensitivity to adrenergic and muscarinic cholinergic stimulation changes as the fetus approaches term, nor the role of the prepartum increase in plasma cortisol concentration in mediating these changes. This study used a novel Langendorff, biventricular, ovine fetal heart preparation to investigate the effects of advancing gestation and cortisol treatment on myocardial sensitivity to adrenergic (isoprenaline) and muscarinic cholinergic (carbachol) stimulation. It was hypothesized that cortisol infusion would fully mimic developmental changes in myocardial responsiveness to adrenergic and cholinergic stimulation. Sixteen Welsh Mountain sheep fetuses were surgically prepared under general anaesthesia with vascular catheters. At 125 +/- 1 days gestational age (dGA; term, 145 dGA) fetuses were infused with saline vehicle (n= 7; Premature Control) or with cortisol (n= 4; 2-3 mg kg(-1) d(-1)i.v.; Premature Cortisol) for 5 days. The Term Control group (n= 5) comprised fetuses that were surgically prepared at 130 dGA and infused with vehicle for 5 days prior to delivery (n= 2), or that received no surgery (n= 3). Under terminal anaesthesia, Premature Control and Premature Cortisol fetuses were delivered at 130 dGA and Term Control fetuses between 135 and 143 dGA. Following exsanguination under anaesthesia, fetal hearts were mounted in the Langendorff preparation, allowing measurement of left ventricular (LV) developed pressure and right ventricular (RV) developed pressure, heart rate (HR), coronary perfusion pressure and perfusate distribution to the myocardium. Cortisol infusion elevated fetal plasma cortisol concentrations to values similar to those measured close to term (45.0 +/- 7.1 ng ml(-1)). Advancing gestational age, but not cortisol treatment, enhanced fetal LV developed pressure, RV developed pressure and HR responses to carbachol (P < 0.05). Advancing gestational age, but not cortisol treatment, suppressed fetal LV developed pressure, RV developed pressure and HR responses to isoprenaline (P < 0.05). Maximum doses of either carbachol or isoprenaline had no effect on coronary perfusate distribution. Changes in myocardial responsiveness to adrenergic and muscarinic cholinergic stimulation with advancing gestation provide mechanisms that contribute to the maturation of the cardiovascular system as the ovine fetus approaches term. These changes in myocardial responsiveness are not solely dependent on preparturient elevations in fetal plasma cortisol concentration.

References

  1. Endocrinology. 1986 Jun;118(6):2510-8 - PubMed
  2. Can J Physiol Pharmacol. 1986 May;64(5):597-601 - PubMed
  3. Am J Physiol. 1999 Jan;276(1 Pt 2):H248-56 - PubMed
  4. Pediatr Res. 1999 Aug;46(2):141-6 - PubMed
  5. Circ Res. 1983 Mar;52(3):263-71 - PubMed
  6. Am J Physiol. 1983 May;244(5):H656-63 - PubMed
  7. Biochim Biophys Acta. 1983 Oct 4;760(1):77-83 - PubMed
  8. Annu Rev Physiol. 1984;46:119-30 - PubMed
  9. Am J Physiol. 1999 Nov;277(5 Pt 2):R1249-60 - PubMed
  10. Am J Physiol. 1986 Nov;251(5 Pt 2):H961-8 - PubMed
  11. Am J Physiol. 1987 Jul;253(1 Pt 2):H184-93 - PubMed
  12. J Dev Physiol. 1987 Jun;9(3):253-69 - PubMed
  13. Pharmacol Toxicol. 1987 Aug;61(2):107-10 - PubMed
  14. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8415-9 - PubMed
  15. Eur J Pharmacol. 1988 Oct 11;155(1-2):101-8 - PubMed
  16. Am J Physiol. 1989 Jul;257(1 Pt 2):H1-9 - PubMed
  17. Circ Res. 1967 Aug;21(2):163-84 - PubMed
  18. Br J Pharmacol. 1990 May;100(1):138-42 - PubMed
  19. Circulation. 1991 Mar;83(3):974-82 - PubMed
  20. J Physiol. 1990 Nov;430:441-52 - PubMed
  21. J Dev Physiol. 1990 Sep;14(3):125-30 - PubMed
  22. Pflugers Arch. 1991 Apr;418(3):266-70 - PubMed
  23. Physiol Bohemoslov. 1990;39(6):481-504 - PubMed
  24. J Dev Physiol. 1991 Oct;16(4):251-61 - PubMed
  25. J Pharmacol Exp Ther. 1992 Jun;261(3):951-8 - PubMed
  26. Pediatr Res. 1992 May;31(5):468-73 - PubMed
  27. Pediatr Res. 1992 Jun;31(6):601-5 - PubMed
  28. Am J Obstet Gynecol. 1992 Aug;167(2):519-23 - PubMed
  29. Circ Res. 1993 Mar;72(3):517-25 - PubMed
  30. J Dev Physiol. 1992 Jun;17(6):289-97 - PubMed
  31. J Appl Physiol (1985). 1993 May;74(5):2585-97 - PubMed
  32. Teratology. 1993 Aug;48(2):169-77 - PubMed
  33. Ann Thorac Surg. 1994 Jun;57(6):1409-15 - PubMed
  34. Cardiovasc Res. 1994 Oct;28(10):1467-75 - PubMed
  35. Ann Thorac Surg. 1995 Mar;59(3):695-8 - PubMed
  36. Anesth Analg. 1995 Jun;80(6):1122-8 - PubMed
  37. Am J Physiol. 1995 Dec;269(6 Pt 2):H2074-81 - PubMed
  38. Am J Physiol. 1996 Feb;270(2 Pt 2):H741-9 - PubMed
  39. Circulation. 1997 Mar 4;95(5):1278-85 - PubMed
  40. Am J Physiol. 1997 Aug;273(2 Pt 2):R457-71 - PubMed
  41. J Cardiovasc Pharmacol. 1997 Oct;30(4):405-11 - PubMed
  42. Hypertension. 1997 Dec;30(6):1376-81 - PubMed
  43. J Appl Physiol (1985). 1998 Jan;84(1):82-9 - PubMed
  44. Proc Nutr Soc. 1998 Feb;57(1):113-22 - PubMed
  45. Pediatr Res. 2000 May;47(5):684-91 - PubMed
  46. J Physiol. 2000 Jul 1;526 Pt 1:167-76 - PubMed
  47. J Appl Physiol. 1971 Oct;31(4):598-604 - PubMed
  48. Circ Res. 1972 Nov;31(5):710-8 - PubMed
  49. Biol Neonate. 1973;22(3):177-88 - PubMed
  50. Am J Obstet Gynecol. 1974 Nov 15;120(6):817-24 - PubMed
  51. Am J Physiol. 1975 Feb;228(2):337-44 - PubMed
  52. Am J Obstet Gynecol. 1977 Dec 1;129(7):748-59 - PubMed
  53. Biol Neonate. 1978;33(3-4):135-43 - PubMed
  54. Br J Pharmacol. 1979 Mar;65(3):431-4 - PubMed
  55. Am J Physiol. 1980 Mar;238(3):H399-405 - PubMed
  56. Endocrinology. 1980 Jul;107(1):155-9 - PubMed
  57. J Pharmacol Exp Ther. 1981 Jan;216(1):6-11 - PubMed
  58. Circ Res. 1981 Feb;48(2):245-53 - PubMed
  59. Br J Pharmacol. 1980 Dec;70(4):515-7 - PubMed
  60. Am J Physiol. 1981 Jul;241(1):H60-6 - PubMed
  61. Basic Res Cardiol. 1981 Nov-Dec;76(6):630-8 - PubMed
  62. Am J Physiol. 1982 Nov;243(5):H729-31 - PubMed
  63. J Clin Invest. 1984 May;73(5):1335-43 - PubMed
  64. Biochemistry. 1984 Nov 20;23(24):5813-21 - PubMed
  65. J Mol Cell Cardiol. 1985 Jan;17(1):31-42 - PubMed
  66. J Pharmacol Exp Ther. 1985 Nov;235(2):335-43 - PubMed

Substances

MeSH terms

Publication Types

Grant support