Intrauterine growth restriction improves cerebral O2 utilization during hypercapnic hypoxia in newborn piglets

Abstract

Data are scant regarding the capacity of cerebrovascular regulation during asphyxia for prevention of brain oxygen deficit in intrauterine growth-restricted (IUGR) newborns. We tested the hypothesis that IUGR improves the ability of neonates to withstand critical periods of severe asphyxia by optimizing brain oxygen supply. Studies were conducted to examine the effects of IUGR on cerebral blood flow (CBF) regulation and oxygen consumption (cerebral metabolic rate for oxygen, CMRO(2)) at different stages of asphyxia (hypercapnic hypoxaemia) in comparison to pure hypoxia (normocapnic hypoxaemia). We used 1-day-old anaesthetized and ventilated piglets. Animals were divided into normal weight (NW) piglets (n = 47; aged 11-26 h, body weight 1481 +/- 121 g) and IUGR piglets (n = 48; aged 13-28 h, body weight 806 +/- 42 g) according to their birth weight. Different stages of hypoxaemia were induced for 1 h by appropriate lowering of the inspired fraction of oxygen (moderate hypoxia: = 31-34 mmHg; severe hypoxia: = 20-22 mmHg). Fourteen NW and 16 IUGR piglets received additionally 9% CO(2) in the breathing gas, so that a of 74-80 mmHg resulted (hypoxia/hypercapnia groups). Eight NW and nine IUGR animals served as untreated controls. Furthermore, affinity of haemoglobin for oxygen was measured under hypoxic and asphyxic conditions. During asphyxia cerebral oxygen extraction was markedly increased in IUGR animals (P < 0.05). This resulted in a significantly diminished CMRO(2)-related increase of CBF at gradually reduced arterial oxygen content (P < 0.05). Therefore, an enhanced effectivity in oxygen availability appeared in newborn IUGR piglets under graded asphyxia by improved cerebral oxygen utilization (P < 0.05). This was not supported by related O(2) affinity of haemoglobin. Thus, IUGR newborns are more capable to ensure brain O(2) demand during asphyxia (hypercapnic hypoxia) than NW neonates.

Figure 1

Effect of gradual normocapnic versus hypercapnic hypoxia on CBF response normalized on brain O₂ demand of normal weight (NW; n= 39, filled symbols/filled columns) and intrauterine growth-restricted (IUGR) piglets (n= 40, open symbols/open columns) in relation to the arterial oxygen content, estimated at the early phase (10th minute) and late phase (50th minute) of the O₂ deficiency period. Values are presented as means +s.d.§P < 0.05, indicates comparison between NW and IUGR piglets. CO, control; mNH, moderate normocapnic hypoxia; sNH, severe normocapnic hypoxia; mHH, moderate hypercapnic hypoxia; sHH, severe hypercapnic hypoxia.

Figure 2

Effect of gradual normocapnic versus hypercapnic hypoxia on cerebrovascular resistance (CVR) in NW (n= 31, filled symbols; regression line: continuous line) and IUGR piglets (n= 31, open symbols; regression line: dashed line) in relation to the arterial blood pressure (ABP) (A), and on cerebral blood flow (CBF) in NW (n= 31, filled symbols; regression line: continuous line) and IUGR piglets (n= 31, open symbols; regression line: dashed line) in relation to the CVR (B), estimated at the early phase (10th minute) and late phase (50th minute) of the O₂ deficiency period. Note that the regression line is plotted, if the independent variable can be used to predict the dependent variable, because the respective regression coefficient was significantly different to zero (P < 0.05).

Figure 3

Effect of normocapnia (NW: n= 8, = 40.2 ± 1.1 mmHg; IUGR: n= 6, = 40.5 ± 1.2 mmHg) and hypercapnia (NW: n= 8, = 78.4 ± 7.5 mmHg; IUGR: n= 8, = 81.2 ± 5.3 mmHg) on the half-saturation oxygen pressure (P₅₀) of normal weight (NW, open columns) and intrauterine growth-restricted newborn piglets (IUGR, filled columns). Values are presented as means +s.d.*‡: P < 0.05. * indicates comparison within every group between normocapnia and hypercapnia; ‡ indicates comparison between NW and IUGR animals.