The role of the sympathetic nervous system in postasphyxial intestinal hypoperfusion in the pre-term sheep fetus

Abstract

Asphyxia in utero in pre-term fetuses is associated with evolving hypoperfusion of the gut after the insult. We examined the role of the sympathetic nervous system (SNS) in mediating this secondary hypoperfusion. Gut blood flow changes were also assessed during postasphyxial seizures. Preterm fetal sheep at 70% of gestation (103-104 days, term is 147 days) underwent sham asphyxia or asphyxia induced by 25 min of complete cord occlusion and fetuses were studied for 3 days afterwards. Phentolamine (10 mg bolus plus 10 mg h(-1)i.v.) or saline was infused for 8 h starting 15 min after the end of asphyxia or sham asphyxia. Phentolamine blocked the fall in superior mesenteric artery blood flow (SMABF) after asphyxia and there was a significant decrease in MAP for the first 3 h of infusion (33 +/- 1.6 mmHg versus vehicle 36.7 +/- 0.8 mmHg, P < 0.005). During seizures SMABF fell significantly (8.3 +/- 2.3 versus 11.4 +/- 2.7 ml min(-1), P < 0.005), and SMABF was more than 10% below baseline for 13.0 +/- 1.7 min per seizure (versus seizure duration of 78.1 +/- 7.2 s). Phentolamine was associated with earlier onset of seizures (5.0 +/- 0.4 versus 7.1 +/- 0.7 h, P < 0.05), but no change in amplitude or duration, and prevented the fall in SMABF. In conclusion, the present study confirms the hypothesis that postasphyxial hypoperfusion of the gut is strongly mediated by the SNS. The data highlight the importance of sympathetic activity in the initial elevation of blood pressure after asphyxia and are consistent with a role for the mesenteric system as a key resistance bed that helps to maintain perfusion in other, more vulnerable systems.

Figure 1. Time sequence of changes in SMABF during the 4 h before occlusion and for 10 h postocclusion

A shows the responses of the asphyxia vehicle group (○) and the asphyxia phentolamine group (•). The groups are further denoted by arrows. Note the biphasic fall in SMABF in the vehicle group, interrupted by a transient period of vasodilatation. Phentolamine causes an initial vasodilatation, but the secondary hypoperfusion phases are prevented. The same transient vasodilatation seen in the asphyxia vehicle group also occurs in the phentolamine group, but the response occurs earlier. B shows the SMABF responses of the sham vehicle group (◯) and sham phentolamine group (•), showing no differences between groups. Data are 1 min averages, means ± s.e.m., *P < 0.05, †P < 0.01 compared to sham vehicle group. The axis break denotes the period of occlusion, not shown.

Figure 2. Examples of changes in EEG, nuchal EMG, MAP and SMABF during seizures

Data are 1 min averages from single fetuses, recorded over 2 h, 3 h after seizures had begun. A shows the response of an asphyxia vehicle group fetus, demonstrating marked vasoconstriction and increased blood pressure during seizures. B shows the response of an asphyxia phentolamine group fetus, showing abolition of both the blood flow and blood pressure responses to each seizure.

Figure 3. Time sequence of changes in MAP during the 4 h before occlusion and for 10 h postocclusion

A shows the responses of the asphyxia vehicle group (○) and the asphyxia phentolamine group (•). The groups are further denoted by arrows. Note the lower blood pressure in the phentolamine group compared to vehicle infusion, and the subsequent further fall in blood pressure corresponding with the transient vasodilatation seen in the phentolamine group in Fig. 1. Similarly, MAP falls in the vehicle group during the same period of vasodilatation, but at a slightly later time. B shows the MAP responses of the sham vehicle group (○) and sham phentolamine group (•), showing no differences between groups. Data are 1 min averages, means ±s.e.m., *P < 0.05, ‡P < 0.005, §P < 0.001 compared to sham vehicle group. The axis break denotes the period of occlusion, not shown.

Figure 4. Time sequence of changes in FHR during the 4 h before occlusion and for 10 h postocclusion

A shows the responses of the asphyxia vehicle group (○) and the asphyxia phentolamine group (•). The groups are further denoted by arrows. Both groups had a similar initial response, but note the earlier onset of tachycardia in the phentolamine group at around 2 h postocclusion, corresponding with the transient period of increased SMABF shown in Fig. 1. Note also the increase in FHR after 4 h in this group, corresponding with the appearance of seizures. B shows the FHR responses of the sham vehicle group (○) and sham phentolamine group (•). Note the tachycardia observed with phentolamine infusion alone, which is not seen in the asphyxia phentolamine group in A. Data are means ± s.e.m., *P < 0.05, †P < 0.01, §P < 0.001 compared to sham vehicle group. The axis break denotes the period of umbilical cord occlusion, not shown.