Early microvascular changes in the preterm neonate: a comparative study of the human and guinea pig

Abstract

Dysfunction of the transition from fetal to neonatal circulatory systems may be a major contributor to poor outcome following preterm birth. Evidence exists in the human for both a period of low flow between 5 and 11 h and a later period of increased flow, suggesting a hypoperfusion-reperfusion cycle over the first 24 h following birth. Little is known about the regulation of peripheral blood flow during this time. The aim of this study was to conduct a comparative study between the human and guinea pig to characterize peripheral microvascular behavior during circulatory transition. Very preterm (≤28 weeks GA), preterm (29-36 weeks GA), and term (≥37 weeks GA) human neonates underwent laser Doppler analysis of skin microvascular blood flow at 6 and 24 h from birth. Guinea pig neonates were delivered prematurely (62 day GA) or at term (68-71 day GA) and laser Doppler analysis of skin microvascular blood flow was assessed every 2 h from birth. In human preterm neonates, there is a period of high microvascular flow at 24 h after birth. No period of low flow was observed at 6 h. In preterm animals, microvascular flow increased after birth, reaching a peak at 10 h postnatal age. Blood flow then steadily decreased, returning to delivery levels by 24 h. Preterm birth was associated with higher baseline microvascular flow throughout the study period in both human and guinea pig neonates. The findings do not support a hypoperfusion-reperfusion cycle in the microcirculation during circulatory transition. The guinea pig model of preterm birth will allow further investigation of the mechanisms underlying microvascular function and dysfunction during the initial extrauterine period.

Keywords: Guinea pig; hypoperfusion–reperfusion; microvascular blood flow; preterm neonate.

Figure 1.

Microvascular blood flow as measured by laser Doppler flowmetry in very preterm (≤28 weeks gestational age; dark gray bars), preterm (29–36 weeks gestational age; light gray bars) and term (≥37 weeks gestational age; open bars) infants. (A) 6 h postnatal age. Microvascular blood flow was highest in very preterm neonates and decreased with advancing gestational age (females P < 0.0001, males P = 0.007). (B) 24 h postnatal age. As at 6 h, blood flow was highest in the most premature infants (females P = 0.0007, males P < 0.0001). (C) 72 h postnatal age. Gestational age differences in microvascular blood flow were observed only in males (P = 0.0007, females P = 0.06). Data are presented as Tukey box and whisker plots (median ± interquartile range [IQR] plus 1.5IQR. Values plotted individually fall outside this range).

Figure 2.

Microvascular blood flow changes over time in very preterm neonates. Microvascular blood flow increased from 6 to 24 h postnatal age in males (hatched bars) and then remained constant to 72 h (P = 0.19). No changes were observed in females (open bars; P = 0.69). *Significance, P = 0.01. Data are presented as Tukey box and whisker plots (median ± interquartile range [IQR] plus 1.5IQR. Values plotted individually fall outside this range).

Figure 3.

Microvascular blood flow over first day of life in neonatal guinea pigs. (A) Microvascular blood flow was significantly higher in male preterm neonates than in female preterm neonates over the study period (P = 0.01). (B) No differences between male and female term neonates were observed. Microvascular blood flow is expressed as log of arbitrary perfusion units (log_ePU) and is presented as mean ± SEM.

Figure 4.

Microvascular blood flow is significantly higher in preterm than term newborn animals. (A) In male animals, preterm neonates had significantly higher microvascular blood flow than term animals over the 24 h study period (P = 0.003). (B) No gestational‐age‐dependent differences were observed in females. Microvascular blood flow is expressed as log of arbitrary perfusion units (log_ePU) and is presented as mean ± SEM.