The effect of hyperoxemia on cerebral blood flow in normal humans

The aim of this study was to evaluate the effect of various degrees of hyperoxemia on cerebral blood flow (CBF), including the hyperbaric oxygenation (HBO) environment. Study subjects were 28 healthy volunteers (17 males and 9 females) from 26 to 60 (average: 42 +/- 11) years old. CBF measurements were done by 19 mCi 133Xe intravenous injection method using rCBF analyzer BI-1400 (Valmet). Two-compartmental analysis was used for the calculation of Fast, Slow Flow and initial slope index (ISI). The three CBF study series included: Rest (before HBO 1 ATA.air)-1 ATA.O2-2 ATA.O2 series in 8 cases; Rest-1 ATA.O2 50% N2 50%-1.5 ATA.O2 series in 10 cases; and Rest-2.5 ATA.O2-after HBO (1 ATA.air) series in 8 cases. CBF measurements commenced 5 to 10 minutes after fixing a mask for oxygen inhalation. Arterial blood gas analyses using IL-813 (IL) and blood pressure measurements were done immediately after CBF measurements. CBF changes evaluated by ISI, estimating resting flow as 100% (PaO2: 93 +/- 8 mmHg), were 91% at 1 ATA.O2 50% (PaO2: 201 +/- 50 mmHg), 79% at 1 ATA.O2 (PaO2: 432 +/- 44 mmHg), 77% at 1.5 ATA.O2 (PaO2: 693 +/-79 mmHg) and 71% at 2 ATA.O2 (PaO2: 838 +/- 95 mmHg). CBF gradually decreased to the level shown for 2 ATA.O2, but CBF showed a tendency to increase somewhat at 2.5 ATA.O2 (81%, PaO2: 1103 +/- 111 mmHg). CBF decreases were statistically significant at 1 ATA.O2, 1.5 ATA.O2, 2 ATA.O2 and also 2.5 ATA.O2 compared with Rest (P less than 0.05). Arterial blood gas analyses clearly showed the stepwise increase in PaO2 to the level of 2.5 ATA.O2 (P less than 0.01). Changes in PaCO2 and blood pressure were slight and not significant statistically in each series. Since the data showed no significant change in the PaCO2 level in each series, it was concluded that the CBF decrease was due to vasoconstriction caused by the elevated PaO2. The mechanism of cerebral vasoconstriction caused by hyperoxemia is not yet clearly understood, but the direct vasoconstrictive effect of oxygen, neurogenic control and the metabolic effect of an elevated cerebral tissue oxygen level may contribute to the CBF decrease. CBF decrease during elevated PaO2 may be a protective physiological response to maintain normal brain metabolism and function against the excessive oxygen supply. Disturbance of this regulatory mechanism may result in oxygen poisoning of the central nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chemiluminescence in hypoxic brain--the first report. Correlation between energy metabolism and free radical reaction

The possibility that cerebral ischemia or cerebral hypoxia may initiate a series of free radical reactions in brain tissue lipid constituents was explored by measuring sequential changes in chemiluminescence values and energy metabolism during brain hypoxia in the rat. Brain hypoxia was induced by means of arterial hypoxemia (PaO2 17-22 mmHg), normocapnia (PaCO2 28-38 mmHg) and normotension (MABP 100-140 mmHg). To obtain lowered PaO2, 4% O2--96% N2 mixed gas was used. Analysis of the chemiluminescence spectra for the purpose of luminous mechanism investigation was again attempted. No peroxidation occurred in the pre-hypoxic state since there were no photon counts. Chemiluminescence began to rise in the hypoxic state and remained at a high value in the post-hypoxic state. Specifically in the hypoxic state, the 3 min period showed 231 +/- 35 counts/10 sec X g (n = 5) and the 5 min period showed 154 +/- 62 (n = 19) counts/10 sec X g. In the post-hypoxic state, the 5 min period showed 217 +/- 79 counts/10 sec X g (n = 9) and the 30 min period showed a decrease similar to the pre-hypoxic state. The chemiluminescence spectroanalysis showed five peaks in wavelength at 480 nm, 520-530 nm, 570 nm, 620-640 nm and 680-700 nm. Sequential changes in energy metabolism revealed that hypoxia caused marked brain lactic acidosis, an increase in both ADP and pyruvate, and a fall in glucose. However, all metabolites recovered at 30 min in the post-hypoxic state, which suggests this was reversible brain hypoxia. Sequential changes in chemiluminescence values and energy metabolism imply the occurrence of free radical reaction in the hypoxic and post-hypoxic brain. The spectroanalysis reveals the luminous mechanism as follows: 1 delta g + 1 delta g----23O2 + h mu     

Chemiluminescence on hypoxic brain--the 1st report: relation between free radical reaction and energy metabolism

To explore the possibility that cerebral ischemia or cerebral hypoxia may initiate a series of free radical reactions of brain tissue lipid constituents, we measured sequential change of chemiluminescence and energy metabolites during brain hypoxia in rat. The hypoxic brain was induced by arterial hypoxemia (PaO2 17-22 mmHg) with normocapnia (PaCO2 28-38 mmHg) and normotension (MABP 100-140 mmHg). 4% O2-96% N2 mixed gas was used as the replacement for obtaining lowered PaO2. We made another attempt to analyze chemiluminescence spectra on purpose of luminous mechanism investigation. No peroxidation occurred in prehypoxic state since there were no photon counts, however, chemiluminescence began to rise up in hypoxic state and remained high value in posthypoxic early state. Namely in hypoxic state, 3-min period showed 231 counts/10 sec X g and 5-min period showed 154 counts/10 sec X g. In posthypoxic state, 5-min period showed 217 counts/10 sec X g and 30-min period showed a similar decrease as prehypoxic state. The chemiluminescence spectroanalysis showed five peaks at 480 nm, 520-530 nm, 570 nm, 620-640 nm, 700 nm in wavelength. As to sequential changes of energy metabolism, hypoxia caused marked brain lactic acidosis, increase in ADP, pyruvate and a fall in glucose. However, all metabolites recovered at 30-min period in posthypoxic state, which suggests this was reversible brain hypoxia. A transition of chemiluminescence and energy metabolites suggests the occurrence of free radical reaction in hypoxic and posthypoxic brain. The spectroanalysis reveals the luminous mechanism as follows 1 delta g # 1 delta g----2(3)O(2) + h nu.     

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.     

Chemiluminescence in hypoxic brain--the second report: cerebral protective effect of mannitol, vitamin E and glucocorticoid

The effect of vitamin E, betamethasone and mannitol upon a series of pathological free radical reactions within hypoxic brain tissue was evaluated by the chemiluminescence method. Hypoxia was induced by arterial hypoxemia (PaO2 17-22 mmHg) with normocapnia (PaCO2 28-38 mmHg) and normotension (MABP 100-140 mmHg). 4% O2-96% N2 mixed gas was used to obtain the lowered PaO2. In the untreated group, increased chemiluminescence was measured in the hypoxic state and the early stage of the initial post-hypoxic state. In the groups administered vitamin E, betamethasone, mannitol and a combination of them reduced chemiluminescence was detected. To explore the reaction stage at which the drugs act in lipid peroxidation, chemiluminescence spectra was analyzed using the brain homogenate with the drugs added. Intensity peaks of the spectra were around at 480, 520-530, 570, 620-640, 680-700 nm before addition of the drugs. All the intensity peaks diminished after addition of vitamin E and betamethasone, but very little decrease occurred after mannitol. The lowered chemiluminescence value may indicate the free radical scavenging action of vitamin E, betamethasone and mannitol in vivo. Chemiluminescence spectrum analysis shows that vitamin E and betamethasone act on the late chain reaction following hydroperoxide and mannitol acts on the early reaction--generation of active oxygens.     

Chemiluminescence on hypoxic brain--the 2nd report: cerebral protective effect of mannitol, vitamin E and betamethasone

The effect of vitamin E, betamethasone and mannitol upon a series of pathological free radical reaction within the hypoxic brain tissue was evaluated by chemiluminescence method. The hypoxic brain was induced by arterial hypoxemia (PaO2 17-22 mmHg) with normocapnia (PaCO2 28-38 mm Hg) and normotension (MABP 100-140 mmHg). 4% O2-96% N2 mixed gas was used as the replacement for obtaining lowered PaO2. In the control group high valued chemiluminescence was measured in the hypoxic state and in the early stage of the initial post-hypoxic state. In the groups administered vitamin E, betamethasone, mannitol and combination of them, however, just extra low valued chemiluminescence was detected. Besides to explore the stage on which the drugs act in lipid peroxidation, chemiluminescence spectra was analyzed using the homogenate added the each drug. Intensity peaks of the spectra were around at 480, 520-530, 570, 620-640, 680-700 nm before addition of the drugs. All the intensity peaks diminished after addition of vitamin E and betamethasone, while in case of mannitol, very little decrease of the intensity peaks was revealed. These experimental results indicate as follows. The lowered chemiluminescence value may prove the possibility of vitamin E, betamethasone and mannitol as free radical scavengers or inhibitor of lipid peroxidation. Chemiluminescence spectro-analysis shows that vitamin E and betamethasone act on the break down of lipid hydroperoxide and mannitol act on hydroxy radical in lipid peroxidation.     

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.     

Hypoxia, hyperoxia, ischemia, and brain necrosis

BACKGROUND: Human brains show widespread necrosis when death occurs after coma due to cardiac arrest, but not after hypoxic coma. It is unclear whether hypoxia alone can cause brain damage without ischemia. The relationship of blood oxygenation and vascular occlusion to brain necrosis is also incompletely defined. METHODS: We used physiologically monitored Wistar rats to explore the relationship among arterial blood oxygen levels, ischemia, and brain necrosis. Hypoxia alone (PaO2 = 25 mm Hg), even at a blood pressure (BP) of 30 mm Hg for 15 minutes, yielded no necrotic neurons. Ischemia alone (unilateral carotid ligation) caused necrosis in 4 of 12 rats, despite a PaO2 > 100 mm Hg. To reveal interactive effects of hypoxia and ischemia, groups were studied with finely graded levels of hypoxia at a fixed BP, and with controlled variation in BP at fixed PaO2. In separate series, focal ischemic stroke was mimicked with transient middle cerebral artery (MCA) occlusion, and the effect of low, normal, and high PaO2 was studied. RESULTS: Quantitated neuropathology worsened with every 10 mm Hg decrement in BP, but the effect of altering PaO2 by 10 mm Hg was not as great, nor as consistent. Autoradiographic study of cerebral blood flow with 14C-iodoantipyrine revealed no hypoxic vasodilatation during ischemia. In the MCA occlusion model, milder hypoxia than in the first series (PaO2 = 46.5 +/- 1.4 mm Hg) exacerbated necrosis to 24.3 +/- 4.7% of the hemisphere from 16.6 +/- 7.0% with normoxia (PaO2 = 120.5 +/- 4.1 mm Hg), whereas hyperoxia (PaO2 = 213.9 +/- 5.8 mm Hg) mitigated hemispheric damage to 7.50 +/- 1.86%. Cortical damage was strikingly sensitive to arterial PaO2, being 12.8 +/- 3.1% of the hemisphere with hypoxia, 7.97 +/-4.63% with normoxia, and only 0.3 +/- 0.2% of the hemisphere with hyperoxia (p < 0.01), and necrosis being eliminated completely in 8 of 10 animals. CONCLUSIONS: Hypoxia without ischemia does not cause brain necrosis but hypoxia exacerbates ischemic necrosis. Hyperoxia potently mitigates brain damage in this MCA occlusion model, especially in neocortex.     

Neurophysiological changes in COPD patients with chronic respiratory insufficiency

Chronic hypoxemia is known to cause peripheral neuropathy (PNP) in chronic obstructive pulmonary disease (COPD) patients. We aimed to know how often PNP is encountered in such patients and the changes in the central nervous system (CNS) if any. We enrolled 32 patients (30 M, 2 F; mean age +/- SD: 61.5 +/- 8.8 years) with COPD into the study. PaO2 > or = 55 mmHg was considered as the cut-off value designating tissue hypoxia. According to this cut-off value the subjects were divided into two groups: Group I, n: 19, PaO2 < 55 mmHg and Group II, n: 13, PaO2 > or = 55 mmHg. All subjects were evaluated with motor and sensory nerve conduction studies (MNCV and SNCV, respectively), electromyography, visual and brainstem evoked potentials (VER and BAER, respectively). We detected PNP in 93.8% of the study subjects. Distal latency of sural nerve correlated significantly with cigarette consumption and reduction in PEFR. SNCV of median nerve was reduced as PaCO2 was elevated and pH was lowered. BAER wave III latency showed significant inverse correlation with PEFR, FEF25 and FEF25-75. Interpeak latency (IPL) of BAER I-III was also significantly and inversely correlated with FEV1/FVC and FEF25-75. IPL of BAER III-V too showed significant correlations with PaCO2, HCO3- and pH of the arterial blood. As BAER III and IPLs of it represent the pontomedullary portion of the brain, cigarette smoking and airways obstruction may not only cause peripheral neuropathy but also a delay in evoked responses of the brain stem by inducing chronic hypercapnia and respiratory acidosis in patients with COPD.     

Interaction between neurogenic and metabolic factors upon deterioration in cerebrovascular tonus--experimental study on the etiology of cerebral vasoparesis

It is widely accepted that a tremendous increase in cerebral blood volume (CBV) due to progressive cerebral vasoparesis is an essential to the development of acute brain swelling. This study was designed to determine whether neurogenic and/or metabolic factors are predominant and how these interact with each other in producing cerebral vasoparesis. Fifty-one awake cats immobilized with pancuronium bromide were divided into 4 groups: group I, control; group II, normocapnic hypoxia (PaO2 = 50 mmHg); group III, normoxic hypercapnia (Pa-CO2 = 70 mmHg), and group IV, increased intracranial pressure (ICP = 40 mmHg) by brain compression. Systemic arterial pressure (BP), CBV (photoelectric method), and ICP (epidural pressure) were continuously recorded. The dorsomedial hypothalamic nucleus (DM) and the reticular formation of the midbrain (MB-RF) were bilaterally coagulated by a stereotaxic technique (3mA, 1 min). Therefore alterations in cerebrovascular tonus created by destruction of the cerebral vasomotor centers were examined in the animals with metabolically induced cerebral vasodilatation to various degree's. In group I, vasomotor center destruction resulted in an immediate and transient decrease in BP (DM; -14.1 +/- 6.7 mmHg, MB-RF; -10.2 +/- 4.8 mmHg) and simultaneous increase in CBV and ICP (DM; 7.6 +/- 7.0 mmHg, MB-RF; 6.0 +/- 5.6 mmHg) for 3 to 4 minutes. Increase in ICP by destruction of vasomotor centers reduced significantly in group II (DM; 2.3 +/- 2.6 mmHg, MB-RF; 1.6 +/- 1.2 mmHg) and reduced slightly in group IV (DM; 7.5 +/- 4.0 mmHg, MB-RF; 4.8 +/- 3.2 mmHg). In these 3 groups, autoregulation of cerebral blood flow and CO2 vasoreactivity were not changed by destruction of vasomotor centers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Initiation and propagation of lipid peroxidation in cerebral infarction models. Experimental studies

The possibility that cerebral ischaemia or cerebral hypoxia may initiate a series of free radical reactions in brain lipid constituents was explored by measuring sequential changes in chemiluminescence (CL) and electron spin resonance (ESR) during hypoxia or ischaemia load. Brain hypoxia was induced by means of arterial hypoxaemia (PaO2 17-22 mmHg), normocapnia (PaCO2 28-38 mmHg) and normotension (MABP 100-140 mmHg). To obtain lowered PaO2, 4% O2-96% N2 mixed gas was used for artificial ventilation. Spin trapping technique was used in ESR measurement and applied to the detection of free radicals generated in the ischaemic brain homogenate of three-vessel occlusion rat model (global highly ischaemic model with basilar artery coagulation and bilateral carotid artery clipping). Chemiluminescence (CL) began to rise in hypoxic or ischaemic loading and indicates high amounts at an early period of post-hypoxic or ischaemic state. The CL spectroanalysis by wavelength showed five peaks at 480 nm, 520-530 nm, 570 nm, 620-640 nm and 680-700 nm in both hypoxic and ischaemic brain. ESR measurement revealed the PBN (phenyl-t-butyl nitrone) trapped radical, which has hyperfine splitting constants of AN = 16.2-16.5 G and AH beta = 3.6-3.8 G in ischaemia model. An analysis of sequential change of PBN adduct intensity shows a peak at 30 min of ischaemic loading and a marked increase in the recirculation period. Preservation of ATP and marked lactic acidosis were seen in the 5 min hypoxic loading, elsewhere depletion of ATP and marked lactic acidosis were seen in the 5 min, 30 min ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantification of glucose utilization in an experimental brain tumor model by the deoxyglucose method

Reevaluation of lumped and rate constants is necessary when Sokoloff's 2-deoxyglucose (DG) method is used to measure glucose utilization in pathological tissue. We describe here a modification of Sokoloff's lumped constant measurement that permits simultaneous estimation of both lumped and rate constants from a single animal experiment. A subcutaneous tumor model (AA ascites tumor) was used for measurement of these constants with a procedure similar to Sokoloff's that kept the plasma tracer concentration constant. Measured constants were as follows: lumped constant, 0.654 +/- 0.081; k1, 0.196 +/- 0.038 min-1; k2, 0.262 +/- 0.067 min-1; k3, 0.117 +/- 0.044 min-1. These constants were used to quantify glucose utilization in the implanted brain tumor. To test the validity of this method, we compared a fraction of the free DG pool calculated using the tumor constants with a fraction measured directly by chromatographic analysis of tissue samples from both subcutaneous tumor and implanted brain tumor. The values derived by chemical analysis agreed well with those predicted by the calculations. The value of k4 varied from 0.0031 +/- 0.0018 min-1 for the tumor tissue to 0.0214 +/- 0.0024 min-1 for tumors with a large necrotic center. This method would be especially useful when applied to xenograft human gliomas in nude mice for quantification of glucose utilization in human gliomas by means of positron emission tomography.     

Effect of hyperventilation on brain tissue oxygenation and cerebrovenous PO2 in rats

Previous studies have shown that cortical tissue oxygenation is impaired during hyperventilation. However, it is important to quantify the effect of hyperventilation on brain tissue PO(2) and cerebrovenous PO(2) simultaneously especially since cerebral venous oxygenation is often used to assess brain tissue oxygenation. The present study was designed to measure the sagittal sinus PO(2) (PvO(2)), brain tissue PO(2) in the thalamus (PtO(2)), and brain temperature (Bt) simultaneously during acute hyperventilation. Isoflurane-anesthetized rats were hyperventilated for 10 min during which time the arterial carbon dioxide tension (PaCO(2)) dropped from 40.3+4.9 mmHg to 23.5+2.8 mmHg. PtO(2) declined from 26.0+/-4.2 mmHg to 14.8+/-5.2 mmHg (P=0.004) while brain temperature decreased from 36.5+0.3 degrees C to 36.2+0.3 degrees C (P=0.02). However, PvO(2) and arterial blood pressure (BP) did not change during hyperventilation. The maintenance of PvO(2) when perfusion is thought to decline and PtO(2) decreases suggests that there may be a diffusion limitation, possibly due to selective perfusion. Therefore, cerebrovenous PO(2) may not give a good assessment of brain tissue oxygenation especially in conditions of acute hyperventilation, and deeper brain regions other than the cortex also show impaired tissue oxygenation following hyperventilation.     

Evening and morning blood gases in patients with obstructive sleep apnea

BACKGROUND AND PURPOSE: The purpose of this study was to see if blood oxygen levels deteriorate overnight during obstructive sleep apnea (OSA). Before and after sleep, arterial blood gases (ABGs) in OSA subjects and controls were drawn during a diagnostic night, as well as during a continuous positive airway pressure (CPAP) night for the OSA subjects. PATIENTS AND METHODS: Subjects, both male and female, were referred to our sleep laboratory for symptoms of daytime somnolence. Subjects consisted of a control group (N=13) with a mean apnea hypopnea index (AHI) of 3.3 events/h and a study group (N=22) with a mean baseline AHI of 57 events/h. RESULTS: With the subject supine, resting room air ABGs were drawn at 'lights out' on the evening before (PM) nocturnal polysomnography and in the morning (AM) at discontinuation ('lights on') of the sleep study. In controls, PM PaO(2) (79.4+/-9.7 mmHg) was not significantly different from AM PaO(2) (80.2+/-8.9 mmHg, P=0.5). In apneic subjects, the PM PaO(2) was 78.7+/-7.2 mmHg compared to an AM PaO(2) of 72.6+/-8.3 mmHg (P<0.05). The AM PaO(2) after a night of CPAP treatment in the OSA subjects was 77.5+/-10.2 mmHg compared to the PM PaO(2) of 76.0+/-6.0 mmHg (NS). The PM and AM PaCO(2)s were not different in controls or in study subjects under baseline conditions. However, during titration with nasal CPAP, the PaCO(2) was significantly higher in the morning after CPAP treatment [43.1+/-4.8 vs. 46.1+/-4.8 mmHg, respectively (P<0.05)]. CONCLUSIONS: OSA subjects showed a fall in overnight resting oxygenation. This could be accounted for by overnight deterioration of gas exchange and is ameliorated by CPAP.     

Effects of hypoxic hypoxia on cerebral phosphate metabolites and pH in the anesthetized infant rabbit

The effects of hypoxic hypoxia on high-energy phosphate metabolites and intracellular pH (pHi) in the brain of the anesthetized infant rabbit were studied in vivo using 31P nuclear magnetic resonance spectroscopy. Five 10- to 16-day-old rabbits were anesthetized with 1.5% halothane. Ventilation was controlled to maintain normocarbia. Inspired O2 fraction was adjusted to produce three states of arterial oxygenation: hyperoxia (PaO2 greater than 250 mm Hg), normoxia (PaO2 approximately 100 mm Hg), and hypoxia (PaO2 25-30 mm Hg). During hypoxia, blood pressure was kept within 20% of control values with a venous infusion of epinephrine. During hyperoxia, the phosphocreatine-to-ATP ratio was 0.86, a value that is 2-2.5 times less than that reported for adults. During normoxia, ATP decreased by 20% and Pi increased by 90% from hyperoxia values. During 60 min of hypoxia, the concentrations of high-energy phosphate metabolites did not change, but intracellular and arterial blood pH (pHa) decreased significantly. When hyperoxia was reestablished, pHi returned to normal and pHa remained low. These results suggest that during periods of hypoxemia, the normotensive infant rabbit maintains intracellular concentrations of cerebral high-energy phosphates better than has been reported for adult animals.     

Apnea test essential in the diagnosis of brain death

We experienced 11 cases of brain death for the past two years, in six of whom we performed the apnea test to confirm the cessation of the medullary respiratory functions. The cause of brain death was primary intracranial lesions in four, subarachnoidal hemorrhages in three and meningitis in one. Hypoxia of the brain secondary to cardiac arrest resulted brain death in the remaining two cases. Blood gases were analysed before (control) and after pre-oxygenation, after having adjusted PaCO2 around 40 mmHg, and every three minutes after disconnection from the respirator. Blood pressure and other vital signs were monitored through out the test. PaCO2 was brought to 40 mmHg by reducing the respiratory rate in three cases, by decreasing the tidal volume following the reduction of the respiratory rate in one case and by applying the bicarbonate gas in one case. The mean PaCO2 level was 46.2 +/- 6.0 mmHg. No one regained the respiration during 10 minutes of the apnea test. In one case, the oxygen catheter was not inserted deeply enough into the tracheal tube, resulting the fall of blood pressure and necessitating termination of the test six minutes after disconnection from the respirator. This case was not included for further analysis. The pH and PaCO2 did not change significantly after pre-oxygenation and after adjusting of PaCO2. Only the PaO2 increased significantly after preoxygenation. PaCO2 increased with the rate of 3.04 +/- 1.2 mmHg/min up to 73.4 +/- 15.6 mmHg and pH decreased with the rate of 0.016 +/- 0.007 down to 7.1 +/- 0.03 after disconnection from the respirator.(ABSTRACT TRUNCATED AT 250 WORDS)     

Selective enhancement of tumor blood flow and drug delivery to brain tumors in experimental rat gliomas under angiotensin II-induced hypertension

Regional blood flow of brain tumors and normal brain tissue of rats before and during angiotensin II (AT II)-induced hypertension were measured using an electrolytic flowmeter and a laser flowmeter. Etoposide concentration in the tumor and brain tissue after intracarotid administration were also measured in brain tumor bearing rats with or without AT II-induced hypertension. A suspension of 5 x 10(5)/10 microliters 9L gliosarcoma cells was inoculated into the left caudate-putamen of CD Fischer 344 rats. Before induced hypertension, regional blood flow of the tumor (28.2 +/- 2.6 ml/100 g/min; mean +/- SEM) and the contralateral caudate-putamen (23.0 +/- 1.8 ml/100g/min) in the tumor bearing rats were significantly lower than that of the caudate-putamen (43.9 +/- 4.1 ml/100g/min) in the normal rats (p less than 0.01). Intravenous administration of AT II at a dose of 0.4-0.6 microgram/body/min increased the mean arterial blood pressure from 96.5 +/- 4.7 mmHg to 138.0 +/- 3.6 mmHg. AT II-induced hypertension resulted in an approximate 1.8(1.1 - 3.6)-fold increase in the regional tumor blood flow. On the other hand the regional blood flow of the contralateral caudate-putamen was slightly decreased at the rate of 6%. The mean concentration of etoposide with AT II-induced hypertension in the tumor tissue was 2.2-fold higher than that without AT II-induced hypertension. However, etoposide delivery to normal brain tissue was small. From these results, induced hypertension with intravenously administrated AT II selectively increase the tumor blood flow and drug delivery to brain tumor tissue. Intracarotid chemotherapy with AT II-induced hypertension might contribute to enhance therapeutic effect of malignant brain tumors.     

Relationship between brain temperature, brain chemistry and oxygen delivery after severe human head injury: the effect of mild hypothermia

We studied brain temperature and the effect of mild hypothermia in 58 patients after severe head injury (SHI). Brain tissue oxygen tension (ptiO2), carbon dioxide tension (ptiCO2), tissuie pH (pHti) and temperature (T.br) were measured using a multiparameter probe. Microdialysis was performed to measure glucose, lactate, glutamate, and aspartate in the extracellular fluid. Mild hypothermia (34 degrees-36 degrees C) was employed in 33 selected patients who had persistent increased intracranial pressure (ICP > 20 mmHg). Mild induced hypothermia decreased brain oxygen significantly from 33 +/- 24 mmHg to 30 +/- 22 mmHg (p < 0.05). The ptiCO2 (46 +/- 8 mmHg) was also significantly lower during mild hypothermia (40.4 +/- 4.0 mmHg), p < 0.0001). The pHti increased from 7.13 +/- 0.15 to 7.24 +/- 0.10 (p < 0.0001) under hypothermic conditions. Induced hypothermia may protect patients from secondary ischemic events by lowering the critical ptiO2 threshold, reducing anaerobic metabolism, and decreasing the release of excitatory aminoacids. However, patients with spontaneous brain hypothermia on admission (Tbr < 36.0 degrees C) showed significantly higher levels of glutamate as well as lactate, compared to all other patients, and had a worse outcome. Spontaneous brain hypothermia carries a poor prognosis, and was characterized by markedly abnormal brain metabolic indices.     

Effects of cerebral air embolism on brain metabolism in pigs

OBJECTIVES: Cerebral air embolism was induced in pigs and changes in intracranial pressure (ICP), brain oxygen (PbrO2), brain carbon dioxide (PbrCO2), brain pH (brpH) and glucose, lactate and pyruvate levels were used to characterize this model. METHODS: In seven anesthetized pigs, ICP, PbrO2, PbrCO2 and brpH were measured continuously with multiparameter sensors and brain glucose metabolism by microdialysis. After injection of air into the internal carotid artery, these parameters were recorded for 2 h. RESULTS: ICP increased (433%) from 12 +/- 1 to 52 +/- 8 mmHg (P < 0.05). PbrO2 decreased from 25.7 +/- 6.2 to 11.9 +/- 5.2 mmHg. PbrCO2 increased (109%) from 57.7 +/- 2.7 to 120.4 +/- 21.5 mmHg (P < 0.05). Brain glucose decreased (38%) from 3.05 +/- 0.91 to 1.91 +/- 0.55 mmol, while brain lactate increased (384%) from 1.36 +/- 0.15 to 5.22 +/- 0.53 mmol/l (P < 0.05). CONCLUSIONS: Cerebral air embolism has a deleterious effect on ICP and brain metabolism. Therefore, this model may be suitable for testing therapeutic regimens in cerebral air embolism.     

A multiparametric assessment of oxygen efflux from the brain.

A quantitative understanding of unidirectional versus net extraction of oxygen in the brain is required because an important factor in calculating oxidative metabolism by calibrated functional magnetic resonance imaging (fMRI) as well as oxygen inhalation methods of positron emission tomography (15O2-PET) and nuclear magnetic resonance (17O2-NMR)) is the degree of oxygen efflux from the brain back into the blood. Because mechanisms of oxygen transport from blood to brain are dependent on cerebral metabolic rate of oxygen consumption (CMRO2), cerebral blood flow (CBF), and oxygen partial pressure (pO2) values in intravascular (Piv) and extravascular (Pev) compartments, we implemented multimodal measurements of these parameters into a compartmental model of oxygen transport and metabolism (i.e., hemoglobin-bound oxygen, oxygen dissolved in plasma and tissue spaces, oxygen metabolized in the mitochondria). In the alpha-chloralose anesthetized rat brain, we used magnetic resonance (7.0 T) and fluorescence quenching methods to measure CMRO2 (2.5+/-1.0 micromol/g min), CBF (0.7+/-0.2 mL/g min), Piv (74+/-10 mm Hg), and Pev (16+/-5 mm Hg) to estimate the degree of oxygen efflux from the brain. In the axially distributed compartmental model, oxygen molecules in blood had two possible fates: enter the tissue space or remain in the same compartment; while in tissue there were three possible fates: enter the blood or the mitochondrial space, or remain in the same compartment. The multiparametric results indicate that the probability of unmetabolized (i.e., dissolved) oxygen molecules reentering the blood from the tissue is negligible and thus its inclusion may unnecessarily complicate calculations of CMRO2 for 15O-PET, 17O-NMR, and calibrated fMRI methods.