Abstract
Introduction:
Microvascular dysfunction, characterized by inappropriate vasodilatation and high blood flow in the peripheral microcirculation, is linked to physiologic instability and poor outcome in neonates. Specifically, preterm neonates have significantly higher levels of baseline microvascular blood flow than term neonates at 24 h postnatal age. Because of similarities between human and guinea pig endocrine profiles and maturity at birth, we hypothesized that preterm guinea pig neonates would provide a suitable model for studying the mechanisms underlying transitional microvascular function.
Results:
Guinea pigs that were delivered preterm showed immaturity and had markedly reduced viability. Baseline microvascular blood flow was significantly higher in preterm animals than in term animals. No effect of intrauterine growth restriction or birth weight on baseline microvascular blood flow was observed in either preterm or term animals.
Discussion:
These results are consistent with recent clinical findings and support the use of the guinea pig as a suitable model for future studies of the mechanisms underlying perinatal microvascular behavior.
Methods:
Guinea pigs were delivered either prematurely or at term. Laser Doppler flowmetry was used to study microvascular blood flow at 23 h postnatal age.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Bhutani VK . Extrauterine adaptations in the newborn. Semin Neonatol 1997; 2: 1–12.
Sinha SK, Donn SM . Fetal-to-neonatal maladaptation. Semin Fetal Neonatal Med 2006;11: 166–73.
Rudolph AM . Circulatory adjustments after birth: effects on ventricular septal defect. Br Heart J 1971;33: Suppl:32–4.
Stark MJ, Clifton VL, Wright IM . Microvascular flow, clinical illness severity and cardiovascular function in the preterm infant. Arch Dis Child Fetal Neonatal Ed 2008;93: F271–4.
Evans N . Assessment and support of the preterm circulation. Early Hum Dev 2006;82: 803–10.
Evans NJ, Archer LN . Postnatal circulatory adaptation in healthy term and preterm neonates. Arch Dis Child 1990;65(1 Spec No): 24–6.
Kluckow M . Low systemic blood flow and pathophysiology of the preterm transitional circulation. Early Hum Dev 2005;81: 429–37.
Stark MJ, Clifton VL, Wright IM . Sex-specific differences in peripheral microvascular blood flow in preterm infants. Pediatr Res 2008;63: 415–9.
Stark MJ, Clifton VL, Wright IM . Neonates born to mothers with preeclampsia exhibit sex-specific alterations in microvascular function. Pediatr Res 2009;65: 292–5.
Smith SD, Tagge EP, Hannakan C, Rowe MI . Characterization of neonatal multisystem organ failure in the surgical newborn. J Pediatr Surg 1991;26: 494–7; discussion 497–9.
Gilbert WM, Danielsen B . Pregnancy outcomes associated with intrauterine growth restriction. Am J Obstet Gynecol 2003;188: 1596–9; discussion 1599–601.
Ishiguro A, Sekine T, Kakiuchi S,et al. Skin and subcutaneous blood flows of very low birth weight infants during the first 3 postnatal days. J Matern Fetal Neonatal Med 2010;23: 522–8.
Martin H, Lindblad B, Norman M . Endothelial function in newborn infants is related to folate levels and birth weight. Pediatrics 2007;119: 1152–8.
Norman M, Martin H . Preterm birth attenuates association between low birth weight and endothelial dysfunction. Circulation 2003;108: 996–1001.
Hanssler L, Roll C, Breukmann H . [Laser Doppler flowmetry in newborn infants with low birth weight. The effect of differences in humidity on peripheral circulation]. Klin Padiatr 1992;204: 359–61.
Martin H, Norman M . Skin microcirculation before and after local warming in infants delivered vaginally or by caesarean section. Acta Paediatr 1997;86: 261–7.
Lafeber HN, Rolph TP, Jones CT . Studies on the growth of the fetal guinea pig. The effects of ligation of the uterine artery on organ growth and development. J Dev Physiol 1984;6: 441–59.
Carter AM, Kingston MJ, Han KK, Mazzuca DM, Nygard K, Han VK . Altered expression of IGFs and IGF-binding proteins during intrauterine growth restriction in guinea pigs. J Endocrinol 2005;184: 179–89.
Langley SC, Kelly FJ . Depletion of pulmonary glutathione using diethylmaleic acid accelerates the development of oxygen-induced lung injury in term and preterm guinea-pig neonates. J Pharm Pharmacol 1994;46: 98–102.
McKendry AA, Palliser HK, Yates DM, Walker DW, Hirst JJ . The effect of betamethasone treatment on neuroactive steroid synthesis in a foetal Guinea pig model of growth restriction. J Neuroendocrinol 2010;22:166–74.
Kaufmann P, Davidoff M . The guinea-pig placenta. Adv Anat Embryol Cell Biol 1977;53: 5–91.
Palliser HK, Zakar T, Symonds IM, Hirst JJ . Progesterone receptor isoform expression in the guinea pig myometrium from normal and growth restricted pregnancies. Reprod Sci 2010;17: 776–82.
Sosenko IR, Frank L . Lung development in the fetal guinea pig: surfactant, morphology, and premature viability. Pediatr Res 1987;21: 427–31.
ENGEL S . The structure of the respiratory tissue in the newly-born. Acta Anat (Basel) 1953;19: 353–65.
Naeye RL, Burt LS, Wright DL, Blanc WA, Tatter D . Neonatal mortality, the male disadvantage. Pediatrics 1971;48: 902–6.
Stephens BE, Vohr BR . Neurodevelopmental outcome of the premature infant. Pediatr Clin North Am 2009;56: 631–46.
Fanaroff AA, Stoll BJ, Wright LL,et al.; NICHD Neonatal Research Network. Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol 2007; 196: 147 e1–8.
Henderson-Smart DJ, Hutchinson JL, Donoghue DA, Evans NJ, Simpson JM, Wright I; Australian and New Zealand Neonatal Network. Prenatal predictors of chronic lung disease in very preterm infants. Arch Dis Child Fetal Neonatal Ed 2006;91: F40–5.
Baenziger O, Jaggi JL, Mueller AC,et al. Cerebral blood flow in preterm infants affected by sex, mechanical ventilation, and intrauterine growth. Pediatr Neurol 1994;11: 319–24.
Chen SJ, Vohr BR, Oh W . Effects of birth order, gender, and intrauterine growth retardation on the outcome of very low birth weight in twins. J Pediatr 1993;123: 132–6.
Davis M, Emory E . Sex differences in neonatal stress reactivity. Child Dev 1995;66: 14–27.
Hoffman EL, Bennett FC . Birth weight less than 800 grams: changing outcomes and influences of gender and gestation number. Pediatrics 1990;86: 27–34.
Ingemarsson I . Gender aspects of preterm birth. BJOG 2003;110: Suppl 20: 34–8.
Fuller PJ, Smith BJ, Rogerson FM . Cortisol resistance in the New World revisited. Trends Endocrinol Metab 2004;15: 296–9.
Owen D, Matthews SG . Repeated maternal glucocorticoid treatment affects activity and hippocampal NMDA receptor expression in juvenile guinea pigs. J Physiol (Lond) 2007;578(Pt 1): 249–57.
Li T, Koshy S, Folkesson HG . IL-1beta-induced cortisol stimulates lung fluid absorption in fetal guinea pigs via SGK-mediated Nedd4-2 inhibition. Am J Physiol Lung Cell Mol Physiol 2009;296: L527–33.
te Pas AB, Siew M, Wallace MJ,et al. Effect of sustained inflation length on establishing functional residual capacity at birth in ventilated premature rabbits. Pediatr Res 2009;66: 295–300.
Leahy MJ, de Mul FF, Nilsson GE, Maniewski R . Principles and practice of the laser-Doppler perfusion technique. Technol Health Care 1999;7: 143–62.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dyson, R., Palliser, H., Kelleher, M. et al. The guinea pig as an animal model for studying perinatal changes in microvascular function. Pediatr Res 71, 20–24 (2012). https://doi.org/10.1038/pr.2011.9
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2011.9