The cardiovascular and cerebrovascular responses of the immature fetal sheep to acute umbilical cord occlusion

Abstract

1. In premature fetal sheep (89-93 days gestation) we examined the fetal response to asphyxia induced by 30 min of complete umbilical cord occlusion. Fetuses were also studied during the first 3 days after asphyxia. We measured heart rate, blood pressure, carotid and femoral blood flows, vascular resistance, electroencephalographic activity and cerebral changes in haemoglobin concentration by near infrared spectroscopy (NIRS). 2. Fetuses tolerated 30 min of asphyxia and the cardiovascular response was characterized by three phases: initial redistribution of blood flow away from the periphery to maintain vital organ function, partial failure of this redistribution and near terminal cardiovascular collapse, with profound hypotension and cerebral and peripheral hypoperfusion. 3. Post-asphyxia carotid blood flow and NIRS data demonstrated that between 3-5 h there was a significant secondary reduction in cerebral blood flow, blood volume and oxygenation despite normal perfusion pressure and heart rate. There was also a secondary fall in femoral blood flow which persisted throughout recovery. 4. These data demonstrate that the immature fetus can survive a prolonged period of asphyxia, but paradoxically the capacity to survive exposes the fetus to profound hypotension and hypoperfusion. A secondary period of significant cerebral hypoperfusion and reduced oxygen delivery also occurred post-asphyxia. These cardiovascular and cerebrovascular responses may contribute to the patterns of cerebral injury seen in the human preterm fetus.

Figure 1. The effect of 30 min of asphyxia induced by complete umbilical cord occlusion on fetal electroencephalographic (EEG) activity, mean arterial blood pressure (MAP) and heart rate (FHR)

Data from the asphyxia group only shown. The shaded region denotes the period of asphyxia. Values are 1 min averages, means ± s.e.m. * P < 0.05, ** P < 0.01, *** P < 0.005, **** P < 0.001, asphyxia group vs. control group (ANCOVA, n = 10 in each group). The horizontal bars show the time periods over which data had the same significance.

Figure 4. The changes in electroencephalographic activity (EEG), mean arterial pressure (MAP) and fetal heart rate (FHR) before and after asphyxia

Data are means ± s.e.m. Data from the control group (○, n = 10) and the occlusion group (•, n = 10) are averaged over 6 h periods before asphyxia, hourly during the first 12 h after asphyxia and over 6 h periods thereafter. The arrow denotes when asphyxia occurred. * P < 0.05, ** P < 0.01, *** P < 0.005, **** P < 0.001, asphyxia group vs. control group by ANCOVA. The horizontal bars show the time periods over which data had the same significance.

Figure 2. The effect of 30 min of asphyxia induced by complete umbilical cord occlusion on fetal carotid and femoral blood flow (CaBF and FBF) and vascular resistance (CaVR and FVR)

Data from the asphyxia group only shown. The shaded region denotes the period of asphyxia. Values are 1 min averages, means ± s.e.m. * P < 0.05, ** P < 0.01, **** P < 0.001, asphyxia group vs. control group by ANCOVA, n = 10 in each group. The horizontal bars show the time periods over which data had the same significance.

Figure 3. The effect of 30 min of asphyxia induced by complete umbilical cord occlusion on total cerebral oxyhaemoglobin (THb, •), deoxyhaemoglobin (Hb, ○) and oxyhaemoglobin (Hb_O2, □) measured by near infrared spectroscopy

Data from the asphyxia group only are shown. Data are 1 min averages, means ± s.e.m. The shaded region denotes the period of asphyxia. The horizontal bars show the time periods over which the data are significantly different from the control group by ANCOVA, n = 5 in each group. * P < 0.05 (THb), ³ P < 0.05 (Hb_O2), ² P < 0.05 (Hb).

Figure 5. The changes in carotid and femoral blood flow (CaBF and FBF) and vascular resistance (CaVR and FVR) before and after asphyxia

Data are means ± s.e.m. Data from the control group (○, n = 10) and the occlusion group (•, n = 10) are averaged over 6 h periods before asphyxia, hourly during the first 12 h after asphyxia and over 6 h periods thereafter. The arrow denotes when asphyxia occurred. * P < 0.05, ** P < 0.01, *** P < 0.005, **** P < 0.001, asphyxia group vs. control group by ANCOVA. The horizontal bars show the time periods over which data had the same significance.

Figure 6. The changes in total cerebral oxyhaemoglobin (THb, •), deoxyhaemoglobin (Hb, ○) and oxyhaemoglobin (Hb_O2, □) before and after asphyxia as measured by near infrared spectroscopy

Data are means ± s.e.m. Data are averaged over 6 h periods before asphyxia, hourly during the first 12 h after asphyxia and over 6 h periods thereafter. The arrow denotes when asphyxia occurred. A, control group (n = 5); B, the occlusion group (n = 5). * P < 0.05, ** P < 0.01, *** P < 0.005, asphyxia group vs. control group by ANCOVA. The horizontal bars show the time periods over which data had the same significance. For clarity only the statistical changes for [THb] are shown.