The role of adenosine in regulation of cerebral blood flow during hypoxia in the near-term fetal sheep

Abstract

The aim of this study was to determine in the near-term ovine fetus the role of adenosine in the basal regulation of cerebral blood flow and in the increases in cerebral blood flow in response to acute hypoxic insult. We measured cerebral blood flow in chronically instrumented fetal sheep (127-135 days gestation, term approximately 145 days) using laser Doppler flowmetry probes implanted in the parietal cortices. Hypoxia was administered for 30 min by lowering the ewe's inspired oxygen to 10-12 % during an infusion of either saline or theophylline, a non-specific adenosine receptor antagonist. The theophylline infusion was begun 30 min prior to and ended 30 min after the completion of the hypoxic insult. The administration of theophylline had no significant effect on cerebral blood flow during the baseline period. During control hypoxic periods, cerebral blood flow increased by approximately 45 %. During theophylline experiments, however, there was no significant increase in cerebral blood flow during hypoxia. In the control experiments, cerebral blood flow returned to baseline levels during the recovery period, while in the theophylline experiments cerebral blood flow fell below baseline levels. We conclude that, in the near-term ovine fetus, adenosine plays a minimal role in the regulation of basal cerebral blood flow. However, these data are strong evidence for the involvement of adenosine in increased fetal cerebral blood flow during an acute hypoxic insult. Finally, adenosine may also play an important role in the maintenance of fetal cerebral blood flow immediately following hypoxic insult.

Figure 1. Effects of hypoxia on cerebral blood flow and cerebral vascular resistance

Cerebral blood flow and cerebral vascular resistance ± s.e.m. during baseline, hypoxia and recovery periods as measured by laser Doppler flowmetry in control (•, n = 12) and theophylline (○, n = 7) experiments. Cerebral vascular resistance was calculated as arterial blood pressure divided by cerebral blood flow (percentage of the baseline). * Significant difference between control and theophylline groups (P < 0.05, two-way ANOVA); † significant difference from mean of pre-infusion period (P < 0.05, one-way ANOVA).

Figure 2. Effects of hypoxia on mean arterial blood pressure and heart rate

Arterial blood pressure and heart rate ± s.e.m. during baseline, hypoxia and recovery periods. * Significant difference between control (•, n = 12) and theophylline (○, n = 7) groups (P < 0.05, two-way ANOVA); † significant difference from mean of pre-infusion period (P < 0.05, one-way ANOVA).

Figure 3. Effects of hypoxia on arterial P_O2, oxygen content and cerebral oxygen delivery

Arterial P_O2, oxygen content and cerebral oxygen delivery ± s.e.m. during baseline, hypoxia and recovery periods. Cerebral oxygen delivery was calculated as the product of arterial oxygen content (percentage of baseline) and laser Doppler flowmetry (percentage of baseline) at the time the blood sample was collected. * Significant difference between control (•, n = 12) and theophylline (○, n = 7) groups (P < 0.05, two-way ANOVA); † significant difference from mean of pre-infusion period (P < 0.05, one-way ANOVA).