PubMed Health⌕ Search

Biomedical subjects

Laura Bennet

Publications and source records attributed to Laura Bennet.

At least 19 recordsLinked to original sources
PubMed2006

Regulation of cytochrome oxidase redox state during umbilical cord occlusion in preterm fetal sheep.

The preterm fetus is capable of surviving prolonged periods of severe hypoxia without neural injury for much longer than at term. To evaluate the hypothesis that regulated suppression of brain metabolism contributes to this remarkable tolerance, we assessed changes in the redox state of cytochrome oxidase (CytOx) relative to cerebral heat production, and cytotoxic edema measured using cerebral impedance, during 25 min of complete umbilical cord occlusion or sham occlusion in fetal sheep at 0.7 gestation. Occlusion was followed by rapid, profound reduction in relative cerebral oxygenation and EEG intensity and an immediate increase in oxidized CytOx, indicating a reduction in electron flow down the mitochondrial electron transfer chain. Confirming rapid suppression of cerebral metabolism there was a loss of the temperature difference between parietal cortex and body at a time when carotid blood flow was maintained at control values. As occlusion continued, severe hypotension/hypoperfusion developed, with a further increase in CytOx levels to a plateau between 8 and 13 min and a progressive rise in cerebral impedance. In conclusion, these data strongly suggest active regulation of cerebral metabolism during the initial response to severe hypoxia, which may help to protect the immature brain from injury.

Animals↗
PubMed2005

Suppression of post-hypoxic-ischemic EEG transients with dizocilpine is associated with partial striatal protection in the preterm fetal sheep.

In vitro studies suggest that glutamate receptor activation is important in the genesis of post-hypoxic preterm brain injury, but there are limited data on post-hypoxic N-methyl-D-aspartate (NMDA) receptor activation. We therefore examined an infusion of the specific, non-competitive NMDA receptor antagonist dizocilpine (2 mg kg(-1) bolus plus 0.07 mg kg(-1) h(-1) i.v.) from 15 min to 4 h after severe hypoxia-ischemia induced by umbilical cord occlusion for 25 min in fetal sheep at 70% of gestation. Dizocilpine suppressed evolving epileptiform transient activity in the first 6 h after reperfusion (2.3 +/- 0.9 versus 9.3 +/- 2.3 maximal counts min(-1), P < 0.05) and mean EEG intensity up to 11 h after occlusion (P < 0.05). Fetal extradural temperature transiently increased during the dizocilpine infusion (40.1 +/- 0.2 versus 39.3 +/- 0.1 degrees C, P < 0.05). After 3 days recovery, treatment was associated with a significant reduction in neuronal loss in the striatum (31 +/- 7 versus 58 +/- 2%, P < 0.05), expression of cleaved caspase-3 (111+/-7 versus 159 +/- 10 counts area(-1), P < 0.05) and numbers of activated microglia (57 +/- 9 versus 92 +/- 16 counts area(-1), P < 0.05); there was no significant effect in other regions or on loss of immature O4-positive oligodendrocytes. In conclusion, abnormal NMDA receptor activation in the first few hours of recovery from hypoxia-ischemia seems to contribute to post-hypoxic striatal damage in the very immature brain.

Animals↗
PubMed2005

Transient NMDA receptor-mediated hypoperfusion following umbilical cord occlusion in preterm fetal sheep.

Exposure to severe hypoxia leads to delayed cerebral and peripheral hypoperfusion. There is evidence in the very immature brain that transient abnormal glutaminergic receptor activity can occur during this phase of recovery. We therefore examined the role of N-methyl-D-aspartate (NMDA) receptor activity in mediating secondary hypoperfusion in preterm fetal sheep at 70% of gestation. Fetuses received either sham asphyxia or asphyxia and were studied for 12 h recovery. The specific, non-competitive NMDA receptor antagonist dizocilpine maleate (2 mg kg-1 bolus plus 0.07 mg kg h-1i.v.) or saline (vehicle) was infused from 15 min after asphyxia until 4 h. In the asphyxia-vehicle group abnormal epileptiform EEG transients were observed during the first 4 h of reperfusion, the peak of which corresponded approximately to the nadir in peripheral and cerebral hypoperfusion. Dizocilpine significantly suppressed this activity (2.7+/-1.3 versus 11.2+/-2.7 counts min-1 at peak frequency, P<0.05) and markedly delayed and attenuated the rise in vascular resistance in both peripheral and cerebral vascular beds observed after asphyxia, effectively preventing the initial deep period of hypoperfusion in carotid blood flow and femoral blood flow (P<0.01). However, while continued infusion did attenuate subsequent transient tachycardia, it did not prevent the development of a secondary phase of persistent but less profound hypoperfusion. In conclusion, the present studies suggest that in the immature brain the initial phase of delayed cerebral and peripheral hypoperfusion following exposure to severe hypoxia is mediated by NMDA receptor activity. The timing of this effect in the cerebral circulation corresponds closely to abnormal EEG activity, suggesting a pathological glutaminergic activation that we speculate is related to evolving brain injury.

Animals↗
PubMed2005

Ontogeny of AMPA and NMDA receptor gene expression in the developing sheep white matter and cerebral cortex.

This study examined the hypothesis that the high prevalence of white matter injury in premature infants is associated with increased expression of calcium-permeable forms of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of glutamate receptors in pre-myelinating white matter. We characterized expression of subunits of the AMPA, and for reference, the N-methyl-d-aspartate (NMDA), glutamate receptors at 0.5, 0.65, 0.85, and term gestation in the ovine fetal white matter and cerebral cortex. There was a low expression of the critical calcium-impermeable AMPA receptor GluR2 subunit in subcortical white matter both absolutely and relative to other AMPA subunits throughout gestation. In contrast, GluR2 subunit mRNA expression fell in the cerebral cortex with increasing gestation whereas protein expression increased. These findings suggest a vulnerability of subcortical white matter to AMPA receptor-mediated calcium toxicity throughout the second half of gestation. Thus, the hypothesis that AMPA receptor-mediated glutamate toxicity contributes to brain damage in premature infants needs to be revised.

Age Factors↗
PubMed2005

Fetal acidosis and hypotension during repeated umbilical cord occlusions are associated with enhanced chemoreflex responses in near-term fetal sheep.

This study examined the hypothesis that repeated episodes of brief but severe hypoxia would not attenuate the chemoreflex-mediated rapid initial fall in fetal heart rate (FHR) and, further, that greater hypoxic stress, as shown by hypotension and metabolic acidosis, would be associated with an enhanced chemoreflex response. Chronically instrumented, near-term fetal sheep received 1 min total umbilical cord occlusion either every 5 min for 4 h (1:5 group; n = 8) or every 2.5 min (1:2.5 group; n = 8) until mean arterial blood pressure fell to <20 mmHg on two successive occlusions. Umbilical cord occlusion caused variable decelerations, with sustained hypertension in the 1:5 group and little change in acid-base status (pH 7.34 +/- 0.03 after 4 h). In contrast, the 1:2.5 group showed progressive hypotension and metabolic acidemia (pH 6.92 +/- 0.04 after the last occlusion). The 1:2.5 group showed a significant increase in the rate of initial fall in FHR during the occlusion series, which was greater than the 1:5 group in the last 30 min of the occlusion series (9.4 +/- 1.4 vs. 3.5 +/- 0.3 beats.min(-1).s(-1); P < 0.01), with a greater fall in FHR (71.9 +/- 6.5 vs. 47.0 +/- 8.7 beats/min; P < 0.05). In summary, this study demonstrated that repetitive laborlike cord occlusions, which led to severe fetal compromise, were associated with an increase in the slope and magnitude of the initial FHR deceleration. These findings support the concept of the chemoreflex as a central, robust component of fetal adaptation to severe hypoxia.

Acidosis↗
PubMed2005

Cortisol and ACTH responses to severe asphyxia in preterm fetal sheep.

It has been hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis is immature in the preterm fetus and that this compromises their ability to adapt to hypoxic stress; however, there are few direct data. We therefore examined the effects of asphyxia on HPA responses in chronically instrumented preterm fetal sheep (104 days of gestation; term is 147 days), allocated to a sham control group (n = 7) or 25 min of complete umbilical cord occlusion (n = 8), followed by recovery for 72 h. During umbilical cord occlusion there was a rapid rise in ACTH levels (230.4 +/- 63.5 versus 14.1 +/- 1.8 ng ml(-1) in sham controls, 16-fold) and cortisol levels (7.4 +/- 4.9 versus 0.2 +/- 0.1 ng ml(-1), 31-fold), with further increases after release of cord occlusion. ACTH levels were normalized by 24 h, while plasma cortisol levels returned to sham control values 72 h after asphyxia. Fetal arterial blood pressure was elevated in the first 36 h, with a marked increase in femoral vascular resistance, and correlated positively with cortisol levels after asphyxia (P = 0.05). In conclusion, the preterm fetus shows a brisk, substantial HPA response to severe hypoxia.

Adrenocorticotropic Hormone↗
PubMed2005

Cortical electroencephalogram suppression is associated with post-ischemic cortical injury in 0.65 gestation fetal sheep.

Suppression of electroencephalogram (EEG) spectral edge (SE) is a suggested marker for preterm white matter (WM) injury; however, there are few specific data. We examined the relationship between SE and EEG intensity and white and grey matter injury after a severe ischemic insult, induced by 30 min carotid occlusion (n=10) compared with sham-control (n=7) in preterm fetal sheep at 95-96 days of gestation (term=147 days). Fetuses were instrumented with a microdialysis probe placed within the left periventricular region and with EEG probes over the parietal cortex bilaterally. Fetuses that showed only brief suppression of the EEG during bilateral carotid occlusion (Mild group, n=4) were compared with those who exhibited persistent suppression (Severe group, n=6). After 72 h recovery, the severe ischemia group showed parasagittal cortical neuronal loss accompanied by diffuse WM damage in the right hemisphere, whereas the mild group showed little or no neuronal loss, either with (n=2) or without diffuse (n=2) WM damage. Left sided focal periventricular WM infarction corresponding with probe placement was seen in all groups. EEG intensity and SE were profoundly suppressed in the severe group, with only partial recovery after 72 h (P<0.01), in contrast with transient suppression in the mild group. There was no difference in baseline SE values or post-ischemic responses between the left and right hemisphere. These findings suggest that persistent suppression of EEG SE is primarily a consequence of cortical grey matter injury.

Action Potentials↗
PubMed2005

Profound hypotension and associated electrocardiographic changes during prolonged cord occlusion in the near term fetal sheep.

OBJECTIVE: To determine whether the onset of fetal hypotension during profound asphyxia is reflected by alterations in the ratio between the T height, measured from the level of the PQ interval, and the QRS amplitude (T/QRS ratio) and ST waveform. STUDY DESIGN: Chronically instrumented near-term fetal sheep received complete occlusion of the umbilical cord for either 8 (n=6) or 15-min (n=9). RESULTS: Cord occlusion led to sustained bradycardia and severe acidosis. Mean arterial blood pressure initially rose and then fell to a nadir of 32.6 +/- 2.6 mm Hg in the 8-min group and 9.3 +/- 1.0 mm Hg in the 15-min group (P < .001). The T/QRS ratio rose initially in parallel with mean arterial blood pressure and then reduced as mean arterial blood pressure fell but remained significantly above baseline. Biphasic ST waveforms during occlusion occurred in only 2 fetuses, but biphasic and negative waveforms occurred during reperfusion in the 15-min group, with a significant rise in troponin T levels (0.58 +/- 0.46 versus 0.02 +/- 0.01 ng/mL at 6 h, P < .01). CONCLUSION: Elevation of the T/QRS ratio does not identify fetal hypotension during severe hypoxia, but abnormal waveforms in the recovery phase may indicate developing cardiac injury.

Acidosis↗
PubMed2005

Spontaneous hypoxia in multiple pregnancies is associated with early fetal decompensation and enhanced T-wave elevation during brief repeated cord occlusion in near-term fetal sheep.

OBJECTIVE: The purpose of this study was to examine the hypothesis that fetuses from multiple pregnancies who exhibited spontaneous, stable hypoxia would show more rapid development of metabolic acidosis and hypotension during short repeated episodes of umbilical cord occlusion than normoxic singleton or twin fetuses and, if this proved to be true, to determine whether this deterioration could be identified by changes in T/QRS height or ST waveform shape. STUDY DESIGN: Chronically instrumented near-term sheep fetuses (124 +/- 1 day) were subjected to 1-minute umbilical cord occlusions every 5 minutes (normoxic group, 8 fetuses; hypoxic group, 10 fetuses) for a total of 4 hours or until mean arterial blood pressure fell below 20 mm Hg for 2 successive occlusions. RESULTS: The spontaneous hypoxic, but not normoxic, fetuses had progressive compromise during repeated umbilical cord occlusions, with severe, progressive metabolic acidosis (pH, 7.07 +/- 0.14; base deficit,13 +/- 1.5 mmol/L vs 7.34 +/- 0.07 mmol/L; base deficit after the final occlusion, 1.1 +/- 1.4 mmol/L; P < .001), and hypotension (24 +/- 2 mm Hg vs 45.5 +/- 3 mm Hg; P < .0001); 4 hypoxic fetuses were unable to complete the 4-hour series of occlusions. The hypoxic group showed a much greater increase in T/QRS ratio during (P < .001) and between occlusions. Biphasic ST segment waveforms were not seen in either group either during or between occlusions. CONCLUSION: Exaggerated elevation of the T/QRS ratio during decelerations in early labor may be a useful marker of greater myocardial anaerobic stress (eg, because of pre-existing spontaneous hypoxia), but not of the development of fetal acidemia or hypotension.

Acidosis↗
PubMed2005

The importance of 'awareness' for understanding fetal pain.

Our understanding of when the fetus can experience pain has been largely shaped by neuroanatomy. However, completion of the cortical nociceptive connections just after mid-gestation is only one part of the story. In addition to critically reviewing evidence for whether the fetus is ever awake or aware, and thus able to truly experience pain, we examine the role of endogenous neuro-inhibitors, such as adenosine and pregnanolone, produced within the feto-placental unit that contribute to fetal sleep states, and thus mediate suppression of fetal awareness. The uncritical view that the nature of presumed fetal pain perception can be assessed by reference to the prematurely born infant is challenged. Rigorously controlled studies of invasive procedures and analgesia in the fetus are required to clarify the impact of fetal nociception on postnatal pain sensitivity and neural development, and the potential benefits or harm of using analgesia in this unique setting.

Adult↗
PubMed2005

The effect of mild hypothermia on insulin-like growth factors after severe asphyxia in the preterm fetal sheep.

OBJECTIVES: Persistent reductions in insulin-like growth factor I (IGF-I) levels in the preterm infant are strongly associated with increased risk of retinopathy and other complications, and may result from exposure to severe hypoxia. The effects of a potential new treatment for hypoxic-ischemic encephalopathy, cerebral hypothermia, on the responses of the IGF axis to hypoxia are unknown. The aim of this study was to examine the effects of prenatal asphyxia and cerebral hypothermia on changes in IGF-I and -II, IGF-binding protein 1 (IGFBP-1), and insulin levels. METHODS: Fetal sheep at 0.7 of gestation underwent either sham asphyxia and sham cooling (n = 7), asphyxia induced by 25 minutes of complete umbilical cord occlusion alone (n = 8), or asphyxia and head cooling (n = 8, extradural temperature 29.5 +/- 2.6C [vs 39.4 +/- 0.3C; P < .05]). Fetuses were studied for 3 days post-insult, during which time fetal blood samples were taken for endocrine measurements. RESULTS: There were no IGF axis changes during occlusion. Plasma IGF-I levels significantly decreased between 6 hours and 48 hours after asphyxia and IGF-II levels by 10 hours, in both asphyxia groups. IGFBP-1 rose from 4 hours, reaching a peak at 10 hours and returning to control values by 48 hours in the normothermia group, and by 24 hours in the hypothermia group. Insulin levels decreased between 2 hours and 10 hours after asphyxia in both asphyxia groups, and subsequently normalized. CONCLUSIONS: This study demonstrates for the first time that transient asphyxia in the preterm sheep fetus is associated with a significant decrease in IGF-II as well as IGF-I during recovery, and that these responses are not altered by mild systemic hypothermia.

Animals↗
PubMed2005

Cerebral oxygenation during postasphyxial seizures in near-term fetal sheep.

After exposure to asphyxia, infants may develop both prolonged, clinically evident seizures and shorter, clinically silent seizures; however, their effect on cerebral tissue oxygenation is unclear. We therefore examined the hypothesis that the increase in oxygen delivery during postasphyxial seizures might be insufficient to meet the needs of increased metabolism, thus causing a fall in tissue oxygenation, in unanesthetized near-term fetal sheep in utero (gestational age 125+/-1 days). Fetuses were administered an infusion of the specific adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, followed by 10 mins of asphyxia induced by complete umbilical cord occlusion. The fetuses then recovered for 3 days. Sixty-one episodes of electrophysiologically defined seizures were identified in five fetuses. Tissue PO(2) (tPO(2)) did not change significantly during short seizures (<3.5 mins), 5.2+/-0.2 versus baseline 5.6+/-0.1 mm Hg (NS), but fell to 2.2+/-0.2 mm Hg during seizures lasting more than 3.5 mins (P<0.001). During prolonged seizures, cortical blood flow did not begin to increase until tPO(2) had begun to fall, and then rose more slowly than the increase in metabolism, with a widening of the brain to blood temperature gradient. In conclusion, in the immature brain, during prolonged, but not short seizures, there is a transient mismatch between cerebral blood flow and metabolism leading to significant cerebral deoxygenation.

Animals↗
PubMed2005

Cardiovascular and endocrine effects of a single course of maternal dexamethasone treatment in preterm fetal sheep.

OBJECTIVE: To determine the effects of a single course of maternally administered dexamethasone on preterm fetal sheep in utero. DESIGN: Prospective randomised controlled trial. SETTING: University laboratory. SAMPLE: Pregnant sheep at 0.7 of gestation. METHODS: Pregnant ewes at 103 days of pregnancy (term = 147 days) were given two intramuscular injections of vehicle (n= 7) or 12 mg of dexamethasone (DEX; n= 8) 24 hours apart. Fetuses were continuously monitored for five days. MAIN OUTCOME MEASURES: Fetal mean arterial blood pressure, carotid and femoral arterial blood flow and vascular resistance, heart rate, heart rate variability, fetal plasma cortisol and ACTH and fetal body movements. RESULTS: DEX injections led to an acute increase in mean arterial blood pressure with a rise in carotid and femoral vascular resistance, a fall in femoral arterial blood flow, and a brief fall in fetal heart rate followed by significant tachycardia. From 24 hours after the injections, mean arterial blood pressure and vascular resistance returned to control values, however, a mild tachycardia [200 (3) vs 184 (4) bpm, P < 0.05] and loss of the circadian pattern of fetal heart rate variability persisted until the end of recording. Plasma ACTH and cortisol were markedly suppressed by DEX (P < 0.05), with values returning to control levels 32 and 72 hours after the first injection, respectively. There was no effect on basal fetal heart rate variability, body movements, carotid arterial blood flow, or the circadian pattern of fetal heart rate. CONCLUSION: In contrast to previous experiments utilising direct fetal infusion of steroids, maternal administration of DEX was associated with only transient hypertension.

Adrenal Cortex↗
PubMed2005

Therapeutic hypothermia: from lab to NICU.

The possibility of a therapeutic role for cerebral hypothermia during or after resuscitation from perinatal asphyxia has been a long-standing focus of research. However, early studies had limited and contradictory results. It is now known that severe hypoxia-ischemia may not cause immediate cell death, but may precipitate a complex biochemical cascade leading to the delayed development of neuronal loss. These phases include a latent phase after reperfusion, with initial recovery of cerebral energy metabolism but EEG suppression, followed by a secondary phase characterized by accumulation of cytotoxins, seizures, cytotoxic edema, and failure of cerebral oxidative metabolism from 6 to 15 h post insult. Although many of the secondary processes can be injurious, they appear to be primarily epiphenomena of the 'execution' phase of cell death. This conceptual framework allows a better understanding of the experimental parameters that determine effective hypothermic neuroprotection, including the timing of initiation of cooling, its duration and the depth of cooling attained. Moderate cerebral hypothermia initiated in the latent phase, between one and as late as 6 h after reperfusion, and continued for a sufficient duration in relation to the severity of the cerebral injury, has been consistently associated with potent, long-lasting neuroprotection in both adult and perinatal species. The results of the first large multicentre randomized trial of head cooling for neonatal encephalopathy and previous phase I and II studies now strongly suggest that prolonged cerebral hypothermia is both generally safe - at least in an intensive care setting - and can improve intact survival up to 18 months of age. Both long-term followup studies and further large studies of whole body cooling are in progress.

Clinical Trials as Topic↗
PubMed2004

Epileptiform activity during rewarming from moderate cerebral hypothermia in the near-term fetal sheep.

Moderate hypothermia is consistently neuroprotective after hypoxic-ischemic insults and is the subject of ongoing clinical trials. In pilot studies, we observed rebound seizure activity in one infant during rewarming from a 72-h period of hypothermia. We therefore quantified the development of EEG-defined seizures during rewarming in an experimental paradigm of delayed cooling for cerebral ischemia. Moderate cerebral hypothermia (n=9) or sham cooling (n=13) was initiated 5.5 h after reperfusion from a 30-min period of bilateral carotid occlusion in near-term fetal sheep and continued for 72 h after the insult. During spontaneous rewarming, fetal extradural temperature rose from 32.5 +/- 0.6 degrees C to control levels (39.4 +/- 0.1 degrees C) in 47 +/- 6 min. Carotid blood flow and mean arterial blood pressure increased transiently during rewarming. The cooling group showed a significant increase in electrical seizure events 2, 3, and 5 h after rewarming, maximal at 2 h (2.9 +/- 1.2 versus 0.5 +/- 0.5 events/h; p <0.05). From 6 h after rewarming, there was no significant difference between the groups. Individual seizures were typically short (28.8 +/- 5.8 s versus 29.0 +/- 6.8 s in sham cooled; NS), and of modest amplitude (35.9 +/- 2.8 versus 38.8 +/- 3.4 microV; NS). Neuronal loss in the parasagittal cortex was significantly reduced in the cooled group (51 +/- 9% versus 91 +/- 5%; p <0.002) and was not correlated with rebound epileptiform activity. In conclusion, rapid rewarming after a prolonged interval of therapeutic hypothermia can be associated with a transient increase in epileptiform events but does not seem to have significant adverse implications for neural outcome.

Adult↗
PubMed2004

Fetal heart rate variability and brain stem injury after asphyxia in preterm fetal sheep.

This study was undertaken to determine the mechanisms mediating changes in fetal heart rate variability (FHRV) during and after exposure to asphyxia in the premature fetus. Preterm fetal sheep at 0.6 of gestation (91 +/- 1 days, term is 147 days) were exposed to either sham occlusion (n = 10) or to complete umbilical cord occlusion for either 20 (n = 7) or 30 min (n = 10). Cord occlusion led to a transient increase in FHRV with abrupt body movements that resolved after 5 min. In the 30 min group there was a marked increase in FHRV in the final 10 min of occlusion related to abnormal atrial activity. After reperfusion, FHRV in both study groups was initially suppressed and progressively increased to baseline levels over the first 4 h of recovery. In the 20 min group this improvement was associated with return of normal EEG activity and movements. In contrast, in the 30 min group the EEG was abnormal with epileptiform activity superimposed on a suppressed background, which was associated with abnormal fetal movements. As the epileptiform activity resolved, FHRV fell and became suppressed for the remainder of the study. Histological assessment after 72 h demonstrated severe brain stem injury in the 30 min group but not in the 20 min group. In conclusion, during early recovery from asphyxia, epileptiform activity and associated abnormal fetal movements related to evolving neural injury can cause a confounding transient increase in FHRV, which mimics the normal pattern of recovery. However, chronic suppression of FHRV was a strong predictor of severe brain stem injury.

Animals↗
PubMed2004

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

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.

Animals↗