The Effect of Mild Hypothermia on Insulin-like Growth Factors After Severe Asphyxia in the Preterm Fetal Sheep
Tóm tắt
Persistent reductions in insulin-like growth factor I (IGF-I) levels in the preterm infant are strongly associated with increased risk of retinopathy and other complications, and may result from exposure to severe hypoxia. The effects of a potential new treatment for hypoxic-ischemic encephalopathy, cerebral hypothermia, on the responses of the IGF axis to hypoxia are unknown. The aim of this study was to examine the effects of prenatal asphyxia and cerebral hypothermia on changes in IGF-I and -II, IGF-binding protein 1 (IGFBP-1), and insulin levels. Fetal sheep at 0.7 of gestation underwent either sham asphyxia and sham cooling (n = 7), asphyxia induced by 25 minutes of complete umbilical cord occlusion alone (n = 8), or asphyxia and head cooling (n = 8, extradural temperature 29.5 ± 2.6C [vs 39.4 ± 0.3C; P <.05]). Fetuses were studied for 3 days post-insult, during which time fetal blood samples were taken for endocrine measurements. There were no IGF axis changes during occlusion. Plasma IGF-I levels significantly decreased between 6 hours and 48 hours after asphyxia and IGF-II levels by 10 hours, in both asphyxia groups. IGFBP-1 rose from 4 hours, reaching a peak at 10 hours and returning to control values by 48 hours in the normothermia group, and by 24 hours in the hypothermia group. Insulin levels decreased between 2 hours and 10 hours after asphyxia in both asphyxia groups, and subsequently normalized. This study demonstrates for the first time that transient asphyxia in the preterm sheep fetus is associated with a significant decrease in IGF-II as well as IGF-I during recovery, and that these responses are not altered by mild systemic hypothermia.
Tài liệu tham khảo
Gunn AJ. Cerebral hypothermia for prevention of brain injury following perinatal asphyxia. Curr Opin Pediatr 2000;12:111–5.
Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia to improve neurode-velopmental outcome following neonatal encephalopathy. Pediatr Res 2004;55:582A.
Sweet MP, Hodgman JE, Pena I, Barton L, Pavlova Z, Ramanathan R. Two-year outcome of infants weighing 600 grams or less at birth and bom 1994 through 1998. Obstet Gynecol 2003;101:18–23.
Thoresen M, Satas S, Loberg EM, et al. Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective. Pediatr Res 2001;50:405–11.
Fant ME, Weisoly D. Insulin and insulin-like growth factors in human development: Implications for the perinatal period. Semin Perinatol 2001;25:426–35.
Ogilvy-Stuart AL, Hands SJ, Adcock CJ, et al. Insulin, insulinlike growth factor I (IGF-I), IGF-binding protein-1, growth hormone, and feeding in the newborn. J Clin Endocrinol Metab 1998;83:3550–7.
Smith WJ, Underwood LE, Keyes L, Clemmons DR. Use of insulin-like growth factor I (IGF-I) and IGF-binding protein measurements to monitor feeding of premature infants. J Clin Endocrinol Metab 1997;82:3982–8.
Kornhauser C, Dubey LA, Garay ME, Perez-Luque EL, Malacara JM, Vargas-Origel A. Serum and urinary insulin-like growth factor-1 and tumor necrosis factor in neonates with and without acute renal failure. Pediatr Nephrol 2002;17:332–6.
Lineham JD, Smith RM, Dahlenburg GW, et al. Circulating insulin-like growth factor I levels in newborn premature and full-term infants followed longitudinally. Early Hum Dev 1986;13:37–46.
Hikino S, Ihara K, Yamamoto J, et al. Physical growth and retinopathy in preterm infants: Involvement of IGF-I and GH. Pediatr Res 2001;50:732–6.
Hellstrom A, Engstrom E, Hard AL, et al. Postnatal serum insulin-like growth factor I deficiency is associated with retinop-athy of prematurity and other complications of premature birth. Pediatrics 2003;112:1016–20.
Smith LE. Pathogenesis of retinopathy of prematurity. Semin Neonatol 2003;8:469–73.
Volpe JJ. Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res 2001;50:553–62.
Low JA. Determining the contribution of asphyxia to brain damage in the neonate. J Obstet Gynaecol Res 2004;30:276–86.
Perlman JM. White matter injury in the preterm infant: An important determination of abnormal neurodevelopment out-come. Early Hum Dev 1998;53:99–120.
Bennet L, Oliver MH, Gunn AJ, Hennies M, Breier B. Differential changes in insulin-like growth factors and their binding proteins following asphyxia in the preterm fetal sheep. J Physiol (Lond) 2001;531:835–41.
McIntosh GH, Baghurst KI, Potter BJ, Hetzel BS. Foetal brain development in the sheep. Neuropathol Appl Neurobiol 1979;5:103–14.
Quaedackers JS, Roelfsema V, Hunter CJ, Heineman E, Gunn AJ, Bennet L. Polyuria and impaired renal blood flow after asphyxia in preterm fetal sheep. AmJ Physiol Regul Integr Comp Physiol 2004;286:R576–83.
Bennet L, Rossenrode S, Gunning MI, Gluckman PD, Gunn AJ. The cardiovascular and cerebrovascular responses of the immature fetal sheep to acute umbilical cord occlusion. J Physiol (Lond) 1999;517:247–57.
Quaedackers JS, Roelfsema V, Heineman E, Gunn AJ, Bennet L. The role of the sympathetic nervous system in post-asphyxial intestinal hypoperfusion in the preterm sheep fetus. J Physiol (Lond) 2004;557(Pt 3):1033–44.
Shen W, Wisniowski P, Ahmed L, Boyle DW, Denne SC, Liechty EA. Protein anabolic effects of insulin and IGF-I in the ovine fetus. AmJ Physiol Endocrinol Metab 2003;284:E748–56.
Bassett NS, Oliver MH, Breier BH, Gluckman PD. The effect of maternal starvation on plasma insulin-like growth factor I con-centrations in the late gestation ovine fetus. Pediatr Res 1990;27:401–4.
Owens JA, Kind KL, Carbone F, Robinson JS, Owens PC. Circulating insulin-like growth factors-I and -II and substrates in fetal sheep following restriction of placental growth. J Endocrinol 1994;140:5–13.
Reik W, Constancia M, Fowden A, et al. Regulation of supply and demand for maternal nutrients in mammals by imprinted genes. J Physiol (Lond) 2003;547:35–44.
Constancia M, Hemberger M, Hughes J, et al. Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature 2002;417:945–8.
Moromisato DY, Moromisato MY, Zanconato S, Roberts CT Jr. Effect of hypoxia on lung, heart, and liver insulin-like growth factor-I gene and receptor expression in the newborn rat. Crit Care Med 1996;24:919–24.
Sugawara J, Tazuke SI, Suen LF, et al. Regulation of insulin-like growth factor-binding protein 1 by hypoxia and 3’,5’-cyclic adenosine monophosphate is additive in HepG2 cells. J Clin Endocrinol Metab 2000;85:3821–7.
Tazuke SI, Mazure NM, SugawaraJ, et al. Hypoxia stimulates insulin-like growth factor binding protein 1 (IGFBP-1) gene expression in HepG2 cells: A possible model for IGFBP-1 expression in fetal hypoxia. Proc Natl Acad Sei USA 1998;95:10188–93.
Unterman TG, Oehler DT, Murphy LJ, Lacson RG. Multihormonal regulation of insulin-like growth factor-binding protein-1 in rat H4IIE hepatoma cells: The dominant role of insulin. Endocrinology 1991;128:2693–701.
Oliver MH, Harding JE, Breier BH, Gluckman PD. Fetal insulin-like growth factor (IGF)-I and IGF-II are regulated differently by glucose or insulin in the sheep fetus. Reprod Fertil Dev 1996;8:167–72.
Jackson BT, Piasecki GJ, Cohn HE, Cohen WR. Control of fetal insulin secretion. Am J Physiol Regul Integr Comp Physiol 2000;279:R2179–88.
Fowden AL. The insulin-like growth factors and feto-placental growth. Placenta 2003;24:803–12.
Roelfsema V, Clark RG. The growth hormone and insulinlike growth factor axis: Its manipulation for the benefit of growth disorders in renal failure. J Am Soc Nephrol 2001;12:1297–1306.
Lewitt MS, Denyer GS, Cooney GJ, Baxter RC. Insulin-like growth factor-binding protein-1 modulates blood glucose levels. Endocrinology 1991;129:2254–6.
Gluckman PD, Gunn TR, Johnston BM. The effect of cooling on breathing and shivering in unanaesthetized fetal lambs in utero. J Physiol (Lond) 1983;343:495–506.
Brink M, Price SR, Chrast J, et al. Angiotensin II induces skeletal muscle wasting through enhanced protein degradation and down-regulates autocrine insulin-like growth factor I. Endocrinology 2001;142:1489–96.