Age-dependent effects of gradual decreases in cerebral perfusion pressure on the neurochemical response in swine (original) (raw)
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Brain oxygenation and metabolism during selective cerebral perfusion in neonates
European Journal of Cardio-thoracic Surgery, 2006
To investigate the possible neuroprotective effects of selective cerebral perfusion (SCP) during deep hypothermic circulatory arrest on brain oxygenation and metabolism in newborn piglets. Methods: Newborn piglets 2-4 days of age, anesthetized and mechanically ventilated, were used for the study. The animals were placed on cardiopulmonary bypass, cooled to 18 8C and put on SCP (20 ml/(kg min)) for 90 min. After rewarming, the animals were monitored through 2 h of recovery. Oxygen pressure in the microvasculature of the cortex was measured by oxygendependent quenching of phosphorescence. The extracellular level of dopamine in striatum was measured by microdialysis and hydroxyl radicals by ortho-tyrosine levels. Levels of phosphorylated cAMP response element binding protein (pCREB) in striatal tissue were measured by Western blots using antibodies specific for phosphorylated CREB. The results are presented as mean AE SD ( p < 0.05 was significant). Results: Pre-bypass cortical oxygen pressure was 48.9 AE 11.3 mmHg and during the first 5 min of SCP, the peak of the histogram, corrected to 18 8C, decreased to 11.2 AE 3.8 mmHg ( p < 0.001) and stayed near that value to the end of bypass. The mean value for the peak of the histograms measured at the end of SCP was 8 AE 3 mmHg ( p < 0.001). SCP completely prevented the deep hypothermic circulatory arrest-dependent increase in extracellular dopamine and hydroxyl radicals. After SCP, there was a statistically significant increase in pCREB immunoreactivity (534 AE 60%) compared to the sham-operated group (100 AE 63%, p < 0.005). Measurements of total CREB showed that SCP did induce a statistically significant increase in CREB as compared to sham-operated animals (168 AE 31%, p < 0.05). Conclusion: SCP, as compared to DHCA, improved cortical oxygenation and prevented increases in the extracellular dopamine and hydroxyl radicals. The increase in pCREB in the striatum following SCP may contribute to improved cellular recovery after this procedure. #
BJA: British Journal of Anaesthesia, 2018
Background: Hypotension is common in anaesthetised children, and its impact on cerebral oxygenation is unknown. The goal of the present study was to investigate the effects of moderate systemic arterial hypotension (mHT) and severe hypotension (sHT) on cerebral perfusion and brain tissue oxygenation in piglets. Methods: Twenty-seven anaesthetised piglets were randomly allocated to a control group, mHT group, or sHT group. Cerebral monitoring comprised a tissue oxygen partial pressure (Pt O2) and laser Doppler (LD) perfusion probe advanced into the brain tissue, and a near-infrared spectroscopy sensor placed over the skin measuring regional oxygen saturation (rSO 2). Arterial hypotension was induced by blood withdrawal and i.v. nitroprusside infusion [target MAP: 35e38 (mHT) and 27e30 (sHT) mm Hg]. Data were analysed at baseline, and every 20 min during and after treatment. Results: Compared with control, Pt O2 decreased equally with mHT and sHT [mean (SD) after 60 min: control: 17.1 (6.4); mHT: 6.4 (3.6); sHT: 7.2 (4.3) mm Hg]. No differences between groups were detected for rSO 2 and LD during treatment. However, in the sHT group, rSO 2 increased after restoring normotension [from 49.3 (9.5) to 58.9 (8.9)% Post60]. sHT was associated with an increase in blood lactate [from 1.5 (0.4) to 2.4 (0.9) mmol L À1 ], and a decrease in bicarbonate [28 (2.4) to 25.8 (2.6) mmol L À1 ] and base excess [4.7 (1.9) to 2.0 (2.7) mmol L À1 ] between baseline and 60 min after the start of the experiment. Conclusions: Induction of mHT and sHT by hypovolaemia and nitroprusside infusion caused alterations in brain tissue oxygenation in a piglet model, but without detectable changes in brain tissue perfusion and regional oxygen saturation.
Stroke, 1999
Background and Purpose-Perinatal hypoxic-ischemic injuries can trigger a cascade of events leading to delayed deterioration and cell death several hours later. The objective of this study was to characterize the cerebral blood flow responses and the changes in extracellular glucose and lactate during the delayed phases of injury and to determine their relationships with the pathophysiological events after hypoxic-ischemic injury. Methods-Two groups of near-term chronically instrumented fetal sheep were subjected to 30 minutes of cerebral hypoperfusion. In the first group, regional cerebral blood flow was measured over the next 24 hours with radiolabeled microspheres. In the second, cortical extracellular glucose and lactate were measured by microdialysis. Parietal electrocorticographic activity and cortical impedance were recorded continuously in both groups, and the extent of neuronal loss was determined histologically at 72 hours after injury. Results-Cerebral blood flow was transiently impaired in the cortex during reperfusion, whereas during the delayed phase, there was a marked increase in cerebral blood flow. The severity of cortical neuronal loss was related to the degree of hypoperfusion in the immediate reperfusion period and inversely related to the magnitude of the delayed hyperperfusion. Cortical extracellular lactate was elevated after injury, and both glucose and lactate secondarily increased during the delayed phase of injury. Conclusions-The delayed phase is accompanied by a period of hyperperfusion that may protect marginally viable tissue.
Neurocritical Care, 2012
Background Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. Monitoring brain tissue oxygenation (B ti pO 2 ) is of considerable clinical interest, but the exact threshold level of ischemia has been difficult to establish due to the complexity of the clinical situation. The objective of this study was to use the Neurovent-PTO (NV) probe, and to define critical cerebral oxygenation-and CPP threshold levels of cerebral ischemia in a standardized brain death model caused by increasing the ICP in pig. Ischemia was defined by a severe increase of cerebral microdialysis (MD) lactate/pyruvate ratio (L/P ratio > 30). Methods B ti pO 2 , L/P ratio, Glucose, Glutamate, Glycerol and CPP were recorded using NV and MD probes during gradual increase of ICP by inflation of an epidural balloon catheter with saline until brain death was achieved. Results Baseline level of B ti pO 2 was 22.9 ± 6.2 mmHg, the L/P ratio 17.7 ± 6.1 and CPP 73 ± 17 mmHg. B ti pO 2 and CPP decreased when intracranial volume was added. The L/P ratio increased above its ischemic levels, (>30) when CPP decreased below 30 mmHg and B ti pO 2 to <10 mmHg. Conclusions A severe increase of ICP leading to CPP below 30 mmHg and B ti pO 2 below 10 mmHg is associated with an increase of the L/P ratio, thus seems to be critical thresholds for cerebral ischemia under these conditions.
Cerebral hypoxia-ischemia in immature rats: Methodological considerations
Experimental Neurology, 1988
We used a model of perinatal hypoxic/ischemic brain damage which combines unilateral common carotid artery ligation and hypoxia (8% 0,). Protein synthesis inhibition and cell loss were found in the ipsilateral forebrain of 1 l-day-old rats when hypoxia was initiated 4 h but not 24 h after carotid ligation. ['4C]Iodoantipyrine up take studies suggest that compensating vascular changes which protect the ipsilateral forebrain occur within 24 h of carotid ligation. o 1988 Academic PI-W, IX.
Cerebral Pressure Autoregulation and Vasoreactivity in the Newborn Rat
Pediatric Research, 2005
Perinatal brain injury has been associated with impaired cerebral blood flow (CBF) pressure autoregulation. The brain of 3-to 5-d-old rat pups is immature and similar to that of a preterm infant, and therefore we tested cerebral vasoreactivity in that animal. CBF pressure autoregulation was tested in 20 Wistar pups during normocapnia and hypercapnia, respectively. Hypotension was induced by hemorrhage and cerebral perfusion was monitored with laser Doppler flowmetry and near-infrared spectroscopy. Systolic blood pressure was measured noninvasively from the tail. During normocapnia, the autoregulatory plateau was narrow. Resting systolic blood pressure (SBP) was 39.2 mm Hg and CBF remained constant until SBP decreased below 36.0 mm Hg (SE 0.8). Below the lower limit, CBF declined by a mean of 2.7% per mm Hg [95% confidence interval (CI), 2.4-3.0%], and hemoglobin difference (HbD) and total hemoglobin (HbT) changed proportionally to CBF. After inhalation of carbon dioxide, CBF increased significantly by a mean of 17.7% (95% CI,
Experimental Brain Research, 2002
Perinatal asphyxia models are necessary to obtain knowledge of the pathophysiology of hypoxia-ischaemia (HI) and to test potential neuroprotective strategies. The present study was performed in newborn piglets to obtain information about simultaneous changes in cerebral oxygenation and haemodynamics and electrocortical brain activity during a 60-min period of HI and up to 2 h of reperfusion using near infrared spectrophotometry (NIRS) and the amplitude-integrated EEG (aEEG). HI was induced by occluding both carotid arteries and decreasing the fraction of inspired oxygen (FiO 2 ) to 0.08-0.12 for 60 min. The mean arterial blood pressure (MABP) and heart rate increased, the oxygenated haemoglobin (O 2 Hb) decreased, and the deoxygenated haemoglobin (HHb) increased, but total haemoglobin (tHb) remained stable during the 60-min HI period. The regional oxygen saturation (rSO 2 ) was significantly decreased during the whole HI period, as was the electrocortical brain activity. Upon reperfusion and reoxygenation, the MABP normalised to baseline values but the heart rate remained increased. O 2 Hb and HHb recovered to baseline values and tHb remained unchanged. As indicated by the unchanged tHb values during the HI period, it was suggested that compensatory cerebral perfusion occurred during this period, probably via the vertebrobasilar arterial system. Furthermore, in this model a clear hyperperfusion period directly upon reperfusion and reoxygenation is not present. rSO 2 showed a quick recovery to baseline values, but the aEEG-measured electrocortical brain activity remained reduced following HI. In conclusion, the rSO 2 and aEEG showed a different time profile following perinatal asphyxia. The stable tHb during HI and reperfusion in this model differs from observations in human neonates.
Neuroscience Letters, 1987
Extracellular levels of excitatory and inhibitory amino acids were measured in the cortex and striatum of asphyxiated fetal lambs. The fetus was exteriorized from the anesthetized ewe and dialysis probes were placed in the parietal cortex and caudate nucleus. Cerebral blood flow was measured with Xe-clearance. Cortical somatosensory-evoked potentials and electroencephalogram (EEG) were continuously recorded. Asphyxia was induced by clamping the umbilical cord or by graded compression of the maternal aorta. Asphyxia accompanied by elevated cerebral blood flow resulted in a moderate rise in extraceUular amino acid levels. During extreme asphyxia, i.e. abolished evoked potentials and reduced cerebral blood flow, marked extracellular elevations of glutamate (3-to 1 l-fold), aspartate (3-to 7-fold), y-aminobutyric acid (GABA) (3-to 5-fold) and taurine (3-to 18-fold) occurred, the higher values representing striatum. Excessive levels of excitatory amino acids may exert injurious effects on immature neurons during such hypoxicischemic states.