Capillary oxygen saturation and tissue oxygen pressure in the rat cortex at different stages of hypoxic hypoxia

The objective of this study was to generate data that allow for estimation of the validity of oxygen saturation (SO2) values in superficial cortical capillaries as calculated by a microreflectometric system (EMPHO II). Capillary SO2 and tissue oxygen pressure (PtO2) were measured simultaneously in the cortex of n = 13 Wistar rats under normocapnic (PaCO2 = 36 mmHg) arterial normoxia (PaO2 = 92 mmHg), moderate (paO2 = 53 mmHg) and severe hypoxic hypoxia (PaO2 = 31 mmHg) with microreflectometry and multiwire surface electrodes. Values were pooled according to arterial oxygenation levels, displayed as frequency histograms and compared via ANOVA (p < 0.05). In a Hill-plot (log PtO2 versus log SO2/(100 - SO2)) an in vivo tissue oxygen dissociation curve was obtained and a linear regression/correlation analysis performed. Mean +/- SD values of SO2 respectively PtO2 decreased from 45.6% +/- 14.6% resp. 26.8 +/- 8.2 mmHg during arterial normoxia to 32.6% +/- 10.2% resp. 20.2 +/- 6.6 mmHg during moderate and to 12.3% +/- 11.1% resp. 8.7 +/- 5.0 mmHg during severe hypoxic hypoxia. Linear regression analysis in the Hill-plot of values between 1% and 65% SO2 and 0.1 and 41 mmHg PtO2 revealed an excellent correlation (r2 = 0.88) with an increase of scatter below 10% SO2 or 1.5 mmHg PtO2. We conclude that SO2 values calculated by the algorithm of the applied microreflectometric system reflect very accurately cortical oxygen supply over a very wide range of oxygenation levels when compared to a gold standard reference. Only at extremely low levels (e.g. below 10% SO2) did we find possible inaccuracies with regard to truly absolute saturation values.     

Endothelin-1 and cerebral blood flow in a porcine model.

The purpose of the study was to investigate whether provoked changes of cerebral perfusion pressure and arterial carbon dioxide tension are able to influence the cerebral metabolism of endothelin-1 (ET-1) in a porcine model. Brain tissue oxygen tension, regional cerebral blood flow and mean arterial blood pressure were monitored in 10 healthy pigs during induced hyperventilation (HV), hypertension (HrT) and hypotension (HoT). ET-1 was determined in the arterial and cerebrovenous blood. Microdialysis samples (lactate, glucose and pyruvate) were taken from brain and subcutaneous tissue. A significant decrease (p<0.05) of the arterial ET-1 (1.46+/-0.33 fmol/mL) compared to the baseline (2.18+/-0.36 fmol/mL) was observed after the HoT-period. We detected a positive correlation between cerebrovenous ET-1 and extracellular cerebral glucose (0.68; p<0.05) after the baseline as well as a negative correlation of -0.81 (p<0.005) between the cerebrovenous ET-1 level and the extracellular cerebral lactate after the HoT-period. These data imply that with increasingly pathological changes of the cerebral metabolism endothelin becomes progressively more important in the regulation of cerebral vascular tone.     

Near-infrared optical responses in feline brain and skeletal muscle tissues during respiratory acid-base imbalance

The effects of hyper- and hypocapnia on oxidative metabolism were evaluated by near-infrared (NIR) multiwavelength spectroscopy in intact brain and skeletal muscle tissues of the anesthetized cat. A 3-wavelength NIR algorithm was used to monitor cytochrome a,a3 oxidation state, regional blood volume, and tissue oxyhemoglobin and O2 stores simultaneously in brain and muscle in ventilated animals. Incremental hypercapnia was produced in 10 cats by raising arterial pCO2 from 27.0 +/- 1.3 to 95.1 +/- 1.9 mmHg with inspired CO2. Hypercapnia produced progressive increases in cerebral HbO2, blood volume, and cytochrome a,a3 oxidation state (P less than 0.01). In contrast, CO2 simultaneously decreased all 3 NIR parameters in intact hindlimb muscles (P less than 0.01). Blood volume changes during hypercapnia correlated with changes in blood flow measured qualitatively by intravascular injections of indocyanine green dye. Hypocapnia produced by hyperventilation in 8 cats lowered paCO2 from 28.5 +/- 0.4 to 13.5 +/- 0.5 mmHg. Hypocapnia decreased cerebral HbO2, blood volume, and cytochrome a,a3 redox level (P less than 0.05), but NIR changes were not seen in skeletal muscle. These experiments demonstrate preferential distribution of oxygen to brain during hypercapnia and the ability of NIR spectroscopy to assess regional oxygenation in multiple tissues non-invasively.     

Influence of moderate and profound hyperventilation on cerebral blood flow, oxygenation and metabolism

OBJECTIVE: The aim of the present study was to examine the impact of moderate and profound hyperventilation on regional cerebral blood flow (rCBF), oxygenation and metabolism. MATERIALS AND METHODS: Twelve anesthetized pigs were subjected to moderate (mHV) and profound (pHV) hyperventilation (target arterial pO(2): 30 and 20 mmHg, respectively) for 30 min each, after baseline normoventilation (BL) for 1 h. Local cerebral extracellular fluid (ECF) concentrations of glucose, lactate, pyruvate and glutamate as well as brain tissue oxygenation (p(ti)O(2)) were monitored using microdialysis and a Licox oxygen sensor, respectively. In nine pigs, regional cerebral blood flow (rCBF) was also continuously measured via a thermal diffusion system. RESULTS: Both moderate and profound hyperventilation resulted in a significant decrease in rCBF (BL: 37.9+/-4.3 ml/100 g/min; mHV: 29.4+/-3.6 ml/100 g/min; pHV: 23.6+/-4.7 ml/100 g/min; p<0.05) and p(ti)O(2) (BL: 22.7+/-4.1 mmHg; mHV: 18.9+/-4.9 mmHg; pHV: 13.0+/-2.2 mmHg; p<0.05). A p(ti)O(2) decrease below the critical threshold of 10 mmHg was induced in three animals by moderate hyperventilation and in five animals by profound hyperventilation. Furthermore, significant increases in lactate (BL: 1.06+/-0.18 mmol/l; mHV: 1.36+/-0.20 mmol/l; pHV: 1.67+/-0.17 mmol/l; p<0.005), pyruvate (BL: 46.4+/-7.8 micromol/l; mHV: 58.0+/-10.3 micromol/l; pHV: 66.1+/-12.7 micromol/l; p<0.05), and lactate/glucose ratio were observed during hyperventilation. (Data are presented as mean+/-S.E.M.) CONCLUSIONS: Both moderate and profound hyperventilation may result in insufficient regional oxygen supply and anaerobic metabolism, even in the uninjured brain. Therefore, the use of hyperventilation cannot be considered as a safe procedure and should either be avoided or used with extreme caution.     

Carotenoid compound crocetin improves cerebral oxygenation in hemorrhaged rats

The carotenoid compound crocetin has been shown to increase oxygen diffusivity in vitro. In the present study the effect of crocetin on tissue oxygenation was examined in the cerebral cortex of rats subjected to hemorrhage. Twelve male Sprague-Dawley rats were anesthetized with pentobarbital and ventilation was controlled (PaCO2 = 33 mm Hg). A craniotomy was performed and the animals were hemorrhaged (20% of estimated total blood volume). Six of 12 animals then received a bolus of crocetin (2 U in 0.1 ml saline); the remaining animals received saline (0.1 ml i.v.) only. Values for mean arterial pressure. PO2, PCO2, pH, and hematocrit did not differ in rats that received either saline or crocetin. Tissue oxygen tension (PtO2) was measured at approximately 170 locations in the parietal cerebral cortex of each rat by a platinum-oxygen microelectrode technique. Results were compared by PtO2 frequency histograms. Crocetin as compared with saline treatment resulted in a right shift of the PtO2 frequency distribution and a significant decrease in the frequency of occurrence of low PtO2 values. The average of individual median PtO2 values was significantly greater in crocetin-treated animals as compared with those receiving saline (7.6 +/- 1.7 vs. 3.2 +/- 1.2 mm Hg, respectively). The results suggest that the carotenoid compound crocetin improves tissue oxygenation in the cerebral cortex of hemorrhaged rats.     

Cerebral oxygen reactivity in the dog

Brain tissue oxygen reactivity is a measure of the increase in tissue oxygen pressure (PtO2) relative to an increase in arterial oxygen pressure (PaO2). Clinical studies show that PtO2 reactivity is increased after cerebral injury. However, the impact of patient ventilation on these measures is not known. We determined whether changes in end tidal carbon dioxide pressure (ETCO2) would affect PtO2 reactivity in dogs. After a craniotomy, a Neurotrend probe that measures PtO2 was inserted into the cerebral cortex of eight dogs. PtO2 reactivity was measured at five concentrations of inspired oxygen (room air, 40%, 60%, 80%, 95%) at three levels of ETCO2 (20 mmHg, 40 mmHg, 60 mmHg) in random order. PtO2 reactivity at ETCO2 of 20 mmHg was 0.2 and increased to 0.3 when ETCO2 was 40 mmHg was 0.4 when ETCO2 was 60 mmHg (p < 0.05). These results show that PtO2 reactivity increases from hypocapnia to normocapnia. It is important to consider the ventilation state of each patient when evaluating PtO2.     

Venous oxygen levels during aerobic forearm exercise: An index of impaired oxidative metabolism in mitochondrial myopathy.

A cardinal feature of impaired skeletal muscle oxidative metabolism in mitochondrial myopathies is a limited ability to increase the extraction of O(2) from blood relative to the increase in O(2) delivery by the circulation during exercise. We investigated whether aerobic forearm exercise would result in an abnormal increase in venous effluent O(2) in patients with impaired skeletal muscle oxidative phosphorylation attributable to mitochondrial disease. We monitored the partial pressure of O(2) (PO(2)) in cubital venous blood at rest, during handgrip exercise, and during recovery in 13 patients with mitochondrial myopathy and exercise intolerance and in 13 healthy control and 11 patient control subjects. Resting and recovery venous effluent PO(2) were similar in all subjects, but during exercise venous PO(2) paradoxically rose in mitochondrial myopathy patients from 27.2 +/- 4.0mmHg to 38.2 +/- 13.3mmHg, whereas PO(2) fell from 27.2 +/- 4.2mmHg to 24.2 +/- 2.7mmHg in healthy subjects and from 27.4 +/- 9.5mmHg to 22.2 +/- 5.2mmHg in patient controls. The range of elevated venous PO(2) during forearm exercise in mitochondrial myopathy patients (32 to 82mmHg) correlated closely with the severity of oxidative impairment as assessed during cycle exercise. We conclude that measurement of venous PO(2) during aerobic forearm exercise provides an easily performed screening test that sensitively detects impaired O(2) use and accurately assesses the severity of oxidative impairment in patients with mitochondrial myopathy and exercise intolerance.     

Mechanisms of cerebrovascular O2 sensitivity from hyperoxia to moderate hypoxia in the rat

Cerebrovascular dilation over PaO2 ranging from hyperoxia to moderate hypoxia is unexplained. We hypothesize that tissue acidosis is the cause. Local cortical cerebral blood flow (LCBF), tissue hydrogen ion concentration [H+]t, and tissue PO2 (PtO2) were measured with microelectrodes in the parietal cortex of 18 rats during a 30-min steady state on 60 to 10% inspired O2 (PaO2, 300 to 40 torr) during 40% N2O analgesia. Five rats kept on 60% O2/40% N2O served as controls. In 18 rats at a PaO2 of 275 +/- 7 torr (mean +/- SEM) and PaCO2 of 35 +/- 1 torr, cerebral values were: LCBF = 129 +/- 23 (mean +/- SEM) ml.100 g-1.min-1; [H+]t = 62 +/- 6 nM; and PtO2 = 25 +/- 3 torr. As PaO2 was reduced from about 300 to 40 torr, changes in these variables in percentage of control with respect to PaO2, were described by the following equations, all at P less than 0.0001: LCBF = 85.9 + 5,572/Pao2; [H+]t = 97.15 + 1,012/PaO2; and PtO2 = 108.8 - 3,492/PaO2. Simultaneous solution of the LCBF and [H+]t equations at various PaO2 revealed a slope of 8.82%/nM. Direct correlation between LCBF in ml.100 g-1.min-1 and [H+]t in nM revealed a linear relationship defined by the equation Y = -7.472 + 1.6705X (r = 0.6426) for [H+]t between 56 and 160 nM (pH = 7.25 and 6.80) but no correlation at [H+]t values between 56 and 32 nM (pH = 7.25 to 7.50). Cerebrovascular tone is directly correlated with [H+]t during progressive, 30-min steady-state reduction in PaO2 from 350 to 40 torr.     

Induced mitochondrial failure in the feline brain: implications for understanding acute post-traumatic metabolic events

OBJECTIVE: Recently, evidence has become available implicating mitochondrial failure as a crucial factor in the pathogenesis of acute brain damage following severe traumatic brain injury (TBI). However, it remains unclear how mitochondrial dysfunction affects cerebral metabolism. Therefore the aim of the study was to evaluate the impact of 'isolated' mitochondrial failure on local cerebral metabolism. METHODS: Cerebral mitochondrial metabolism was blocked by local microdialysis perfusion with cyanide in seven cats. Local brain tissue oxygen tension (p(tiO(2))), carbon dioxide tension (p(tiCO(2))) and pH, as well as extracellular cerebral fluid, glucose, lactate, pyruvate and glutamate were monitored, using a Neurotrend sensor and microdialysis, respectively. Tissue oxygen consumption was measured in a microrespirometric system, and ultrastructural changes evaluated via electron microscopy. RESULTS: Brain tissue oxygen tension increased from a baseline of 31+/-9 mmHg to 84+/-30 mmHg after 60 min of cyanide perfusion (P<0.05), concomitant a decrease in oxygen consumption from 14.45+/-3.91 microl/h/mg to 10.83+/-1.74 microl/h/mg (P<0.05). Brain tissue pH was decreased after 60 min of cyanide perfusion (6.83+/-0.16) compared to baseline (7.07+/-0.39) (P<0.05), whereas p(tiCO(2)) did not show significant changes. Lactate massively increased from a baseline of 599+/-270 micromol/l to 2609+/-1188 micromol/l immediately after cyanide perfusion (P<0.05). The lactate:glucose ratio increased from 0.79+/-0.15 before cyanide perfusion to 6.40+/-1.44 at 40 min after cyanide perfusion (P<0.05), while no significant changes in the lactate:pyruvate ratio could be observed. Glutamate increased from a baseline of 11.6+/-7.2 micromol/l to 61.4+/-44.7 micromol/l after cyanide perfusion (P<0.05). CONCLUSION: The results of this study show that 'isolated' cerebral mitochondrial failure initiates changes in cerebral substrates and biochemistry, which are very similar to most of the changes seen after severe human head injury, except for the early fall in p(tiO(2)), further indicating a crucial involvement of mitochondrial impairment in the development of brain damage after TBI.     

Capillary-oxygenation-level-dependent near-infrared spectrometry in frontal lobe of humans.

Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation (SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve healthy subjects (20 to 29 years), supine and seated, inhaled O2 air-mixtures (10% to 100%) with and without added 5% carbon dioxide and during hyperventilation. Two measures of frontal lobe oxygenation by NIRS (NIRO-200 and INVOS) were compared with capillary oxygen saturation (SCap) as calculated from the O2 content of brachial arterial and right internal jugular venous blood. At control SCap (78%+/-4%; mean+/-s.d.) was halfway between the arterial (98%+/-1%) and jugular venous oxygenation (SvO2; 61%+/-6%). Both NIRS devices monitored SCap (P<0.001) within approximately 5% as SvO2 increased from 39%+/-5% to 79%+/-7% with an increase in the transcranial ultrasound Doppler determined middle cerebral artery flow velocity from 29+/-8 to 65+/-15 cm/sec. When SCap fell below approximately 70% with reduced flow and inspired oxygen tension, PMitoO2 decreased (P<0.001) and brain lactate release increased concomitantly (P<0.001). Handgrip strength correlated with the measured (NIRS) and calculated capillary oxygenation values as well as with PMitoO2 (r>0.74; P<0.05). These results show that NIRS is an adequate cerebral capillary-oxygenation-level-dependent (COLD) measure during manipulation of cerebral blood flow or inspired oxygen tension, or both, and suggest that motor performance correlates with the frontal lobe COLD signal.     

Multiparameter brain tissue monitoring--correlation between parameters and identification of CPP thresholds

Continuous monitoring of brain interstitial gas concentrations allows direct regional evaluation of the pathophysiology of cerebral tissues. We have incorporated the Paratrend 7 (P7) multiparameter sensor into our established multimodal monitoring of head injured patients, to investigate the relationship between brain and arterial pO2, pCO2, and pH, as well as defining thresholds for cerebral perfusion pressure (CPP). A P7 sensor was inserted into the brain tissue of 40 adult head injured patients via a modified Camino bolt or triple lumen bolt. A second sensor was placed in the femoral artery for continuous monitoring of blood gases. Data signals from 19 monitored parameters were collected onto computer at the bedside for up to 14 days. No complications were seen. For individual patients the changes in brain tissue parameters showed large variations over 24 hours and the relationship between parameters varied considerably both between patients and during the period of monitoring any one individual. Changes related to periods of arterial desaturation, cerebral hypoperfusion and therapeutic manoeuvres could be seen. Good correlation was seen between brain pCO2 and arterial pCO2 (r = 0.58). Poor correlation was seen between CPP and brain pO2, and between brain pO2 and ICP. However, by grouping values for intracranial pressure (ICP) and CPP, thresholds for brain tissue pO2 were identified in 16 patients where CPP fell below 60 mmHg. No patients where CPP was always > 60 mmHg showed a significant threshold for a drop in brain pO2 (n = 16). In conclusion, the P7 shows potential as a monitor of regional brain oxygenation and for detection of potentially damaging secondary insults. The results must be interpreted whilst considering catheter position, autoregulation and systemic arterial changes for each individual.     

Prospects for investigating brain oxygenation in acute stroke: Experience with a non‐contrast quantitative BOLD based approach

Metabolic markers of baseline brain oxygenation and tissue perfusion have an important role to play in the early identification of ischaemic tissue in acute stroke. Although well established MRI techniques exist for mapping brain perfusion, quantitative imaging of brain oxygenation is poorly served. Streamlined‐qBOLD (sqBOLD) is a recently developed technique for mapping oxygenation that is well suited to the challenge of investigating acute stroke. In this study a noninvasive serial imaging protocol was implemented, incorporating sqBOLD and arterial spin labelling to map blood oxygenation and perfusion, respectively. The utility of these parameters was investigated using imaging based definitions of tissue outcome (ischaemic core, infarct growth and contralateral tissue). Voxel wise analysis revealed significant differences between all tissue outcomes using pairwise comparisons for the transverse reversible relaxation rate (R ₂′), deoxygenated blood volume (DBV) and deoxyghaemoglobin concentration ([dHb]; p < 0.01 in all cases). At the patient level (n = 9), a significant difference was observed for [dHb] between ischaemic core and contralateral tissue. Furthermore, serial analysis at the patient level (n = 6) revealed significant changes in R ₂′ between the presentation and 1 week scans for both ischaemic core (p < 0.01) and infarct growth (p < 0.05). In conclusion, this study presents evidence supporting the potential of sqBOLD for imaging oxygenation in stroke.     

Diagnosis and management of increased intracranial pressure

Increased intracranial pressure (ICP) is a pathological state common to a variety of neurological diseases, all of which are characterized by the addition of volume to the skull contents. Elevated ICP may lead to brain damage or death by two principle mechanisms: 1) global hypoxic-ischemic injury, as a consequence of reduced cerebral perfusion pressure (CPP) and cerebral blood flow; and 2) mechanical distortion and compression of brain tissue as a result of intracranial mass effect and ICP compartmentalization. All ICP therapies have as a goal, reduction of intracranial volume. In unmonitored patients with acute neurological deterioration, head elevation, hyperventilation, and mannitol (1g/kg) can rapidly lower ICP. Fluid-coupled ventricular catheters and fiberoptic transducers are the most accurate and reliable instruments for measuring ICP. In monitored patients, the treatment of critically raised ICP should proceed in an orderly step-wise fashion: 1) consideration of neuroimaging to exclude a new surgically operable lesion; 2) intravenous sedation to attain a quiet motionless state; 3) manipulation of blood pressure to keep CPP >70 and <120; 4) mannitol infusion; 5) moderate hyperventilation (P(CO2) 26 to 30 mmHg); and 6) high-dose pentobarbital therapy. Application of moderate hypothermia (32 to 33 degrees C) shows promise as a newer method for treating refractory ICP. Placement of an ICP monitor is the critical first step in management of ICP. Treatment is best done using a stepwise protocol, with careful attention to sedation and CPP control prior to using mannitol and hyperventilation.     

Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension

BACKGROUND: Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE: To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN: A randomized controlled trial. SETTING: Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS: Twenty healthy little pigs, either male or female, weighing 4.5–5.5 kg, were used. Neurotrend-typed multiparameter monitoring system (Diametrics Company, British); CMA/100 micro-injection pump (Carnegie Company, Sweden). METHODS: The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups: the normothermia group (control group, n =10) and moderate hypothermia group (n =10). ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure (MEP), and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of carbon dioxide (PaCO2), HCO3–]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure (CPP, CPP=MAP(ICP), brain tissue partial oxygen pressure (PO2), partial pressure of carbon dioxide (PCO2), HCO3– and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33–35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES: ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS: All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation: In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [(3.31±1.19), (5.33±0.95) kPa, P < 0.05], CCP was higher, brain tissue PCO2 [(12.03±1.73), (10.59±2.01) kPa, P < 0.05], and brain tissue pH value was higher [(7.03±1.63), (9.40±1.30) kPa, P < 0.05], whereas the brain temperature was decreased as compared with that before cooling [(34.9±0.3), (37.2±0.2) ℃, P < 0.05]. ② Results of blood gases analysis in the moderate hypothermia group: There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group (P > 0.05) CONCLUSION: Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.     

Noninvasive assessment of cerebral oxygenation during acclimation to hypobaric hypoxia.

Factors regulating cerebral tissue PO2 (PtO2) are complex. With the increased use of clinical PtO2 monitors, it has become important to elucidate these mechanisms. The authors are investigating a new methodology (electron paramagnetic resonance oximetry) for use in monitoring cerebral PtO2 in awake animals over time courses of weeks. The authors used this to study cerebral PtO2 in rats during chronic acclimation to hypoxia predicting that such acclimation would cause an increase in PtO2 because of increases that occur in capillary density and oxygen carrying capacity. The average PtO2 between 7 and 21 days was increased by 228% over controls.     

Cerebral effects of extended hyperventilation in unanesthetized goats

Thirty-six adult, male unanesthetized goats were hyperventilated to a PaCO2 level of 16-18 mm Hg for 6 hours. Arterial and sagittal sinus blood and cerebrospinal fluid were analyzed for pH, blood gases, bicarbonate, lactate, and pyruvate before hyperventilation, during hyperventilation, and after the termination of hyperventilation. Total cerebral blood flow, regional brain blood flows, and cerebral metabolic rate for oxygen were calculated from the distribution of radioactive microspheres. Intracranial pressure was measured in either the right or left cerebral ventricle. With the initiation of hyperventilation, cerebral blood flow and cerebral metabolic rate for oxygen fell significantly (64 +/- 5 ml/100 g/min to 41 +/- 3; 4.6 +/- 0.3 ml O2/100 g/min to 3.6 +/- 0.2), but both returned to prehyperventilation values within 6 hours of hyperventilation. With termination of hyperventilation, cerebral blood flow and cerebral metabolic rate for oxygen increased significantly above control levels (64 +/- 5 vs. 105 +/- 9; 4.6 +/- 0.3 vs. 5.4 +/- 0.4). Intracranial pressure was unaffected by hyperventilation or its termination. Arterial and sagittal sinus blood and cerebrospinal fluid pH increased with hyperventilation but returned to control values by 6 hours. However, pH was still significantly elevated at 6 hours. Lactate and pyruvate followed a similar pattern except in the cerebrospinal fluid, where both increased throughout the course of hyperventilation. There were no significant differences in the lactate:pyruvate ratio. On termination of hyperventilation, pH of the arterial and sagittal sinus blood and cerebrospinal fluid fell below control levels. Bicarbonate values decreased in all fluid compartments and were still below control values 2 hours after the cessation of hyperventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of short-term hyperventilation on cerebral blood flow autoregulation in patients with acute bacterial meningitis

BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) autoregulation is impaired in patients with acute bacterial meningitis: this may be caused by cerebral arteriolar dilatation. We tested the hypothesis that CBF autoregulation is recovered by acute mechanical hyperventilation in 9 adult patients with acute bacterial meningitis. METHODS: Norepinephrine was infused to increase mean arterial pressure (MAP) 30 mm Hg from baseline. Relative changes in CBF were concomitantly recorded by transcranial Doppler ultrasonography of the middle cerebral artery, measuring mean flow velocity (V(mean)), and by measurement of arterial to jugular oxygen content difference (a-v DO(2)). The slope of the regression line between MAP and V(mean) was calculated. Measurements were performed during normoventilation and repeated after 30 minutes of mechanical hyperventilation. RESULTS: At normoventilation (median PaCO(2) 4.4 kPa, range 3.5 to 4.9), MAP was increased from 68 mm Hg (60 to 101) to 109 mm Hg (95 to 126). V(mean) increased with MAP from 48 cm/s (30 to 61) to 65 cm/s(33 to 86) (P<0.01), and a-v DO(2) decreased from 2.2 mmol/L (1.0 to 2.7) to 1.4 mmol/L (0.8 to 1.8) (P<0.05). During hyperventilation (PaCO(2) 3.5 kPa, range 3.3 to 4.1), MAP was increased from 76 mm Hg (58 to 92) to 109 mm Hg (95 to 121). V(mean) increased from 45 cm/s (29 to 55) to 53 cm/s (33 to 78) (P<0.01), and a-v DO(2) decreased from 2.5 mmol/L (1.8 to 3.0) to 1.8 mmol/L (1.2 to 2.4) (P<0.05). Four patients recovered autoregulation completely during hyperventilation. The slope of the autoregulation curve decreased during hyperventilation compared with normoventilation (P<0.05). CONCLUSIONS: CBF autoregulation is partially recovered during short-term mechanical hyperventilation in patients with acute bacterial meningitis, indicating that cerebral arteriolar dilation in part accounts for the regulatory impairment of CBF in these patients.     

Differential approach to the application of hyperventilation in acute period of severe brain injury in relation to cerebral circulation

Seventeen patients with severe brain injury (Glasgow-8 Coma Scale 3-8 scores) complicated by traumatic subarachnoidal hemorrhage and severe cerebral hemodynamic disorders (hyperemia, vasospasm) were examined. Hyperventilation was performed in different phases of cerebral circulation under multiparametrical monitoring (intracranial pressure, cerebral perfusion pressure, jugular oximetry, Doppler study using the carotid compression test). The use of hyperventilation to eliminate intracranial hypertension in victims with brain hyperemia was shown to make cerebral circulation consistent with brain tissue oxygen demands and to improve the autoregulatory reserve of cerebral vessels. The application of hyperventilation to eliminate intracranial hypertension in vasospasm leads to a temporary reduction in intracranial pressure, but simultaneously causes cerebral circulatory changes that do not correspond to cerebral oxygen demands, as well as lowered cerebral perfusion pressure, which increases a risk for ischemic brain tissue lesion. This requires a strict rationale for the use of hyperventilation and for multiparametrical monitoring of cerebral functions, which includes jugular oximetry, Doppler transcranial study, and measurement of intracranial pressure throughout the hyperventilation period in order to prevent secondary brain lesion.     

Simultaneous measurement of brain tissue oxygen partial pressure, temperature, and global oxygen consumption during hibernation, arousal, and euthermy in non-sedated and non-anesthetized Arctic ground squirrels

This study reports an online temperature correction method for determining tissue oxygen partial pressure [Formula: see text] in the striatum and a novel simultaneous measurement of brain [Formula: see text] and temperature (T(brain)) in conjunction with global oxygen consumption [Formula: see text] in non-sedated and non-anesthetized freely moving Arctic ground squirrels (AGS, Spermophilus parryii). This method fills an important research gap-the lack of a suitable method for physiologic studies of tissue [Formula: see text] in hibernating or other cool-blooded species. [Formula: see text] in AGS brain during euthermy (21.22+/-2.06mmHg) is significantly higher (P=0.016) than during hibernation (13.21+/-0.46mmHg) suggests brain oxygenation in the striatum is normoxic during euthermy and hypoxic during hibernation. These results in [Formula: see text] are different from blood oxygen partial pressure [Formula: see text] in AGS, which are significantly lower during euthermy than during hibernation and are actually hypoxic during euthermy and normoxic during hibernation in our previous study. This intriguing difference between the [Formula: see text] of brain tissue and blood during these two physiological states suggests that regional mechanisms in the brain play a role in maintaining tissue oxygenation and protect against hypoxia during hibernation.     

Acute cerebral tissue oxygenation changes following experimental subarachnoid hemorrhage

Primary brain ischemia following subarachnoid hemorrhage is a major cause of morbidity and mortality. This study aims to determine whether changes in cerebral tissue oxygenation are related to cerebral blood flow changes in the acute phase following experimental subarachnoid hemorrhage. The endovascular puncture model was used to study subarachnoid hemorrhage in male Wistar rats with a tissue oxygenation probe and a laser Doppler probe placed contralateral to the side of hemorrhage. Following the subarachnoid hemorrhage intracranial pressure rose to 53.0 +/- 9.8 mmHg (mean +/- SEM). This was associated with a fall in cerebral blood flow to 43.9% +/- 7.1% of its baseline value and a fall in tissue oxygenation to 42.8% +/- 7.7% of baseline. The time course of the fall and recovery in tissue oxygenation was closely correlated to that of the cerebral blood flow (r = 0.66, p = 0.02). The fall in cerebral blood flow was associated with a 42.1% +/- 6.47% fall in the concentration of moving blood cells and a rise of 181.2% +/- 27.2% in velocity indicating acute microcirculatory vasoconstriction. Interstitial tissue oxygenation changes mirrored changes in cerebral blood flow indicating that a change in oxygen delivery was occurring.