Hyperbaric oxygen therapy protects against mitochondrial dysfunction and delays onset of motor neuron disease in Wobbler mice.

The Wobbler mouse is a model of human motor neuron disease. Recently we reported the impairment of mitochondrial complex IV in Wobbler mouse CNS, including motor cortex and spinal cord. The present study was designed to test the effect of hyperbaric oxygen therapy (HBOT) on (1) mitochondrial functions in young Wobbler mice, and (2) the onset and progression of the disease with aging. HBOT was carried out at 2 atmospheres absolute (2 ATA) oxygen for 1 h/day for 30 days. Control groups consisted of both untreated Wobbler mice and non-diseased Wobbler mice. The rate of respiration for complex IV in mitochondria isolated from motor cortex was improved by 40% (P<0.05) after HBOT. The onset and progression of the disease in the Wobbler mice was studied using litters of pups from proven heterozygous breeding pairs, which were treated from birth with 2 ATA HBOT for 1 h/day 6 days a week for the animals' lifetime. A "blinded" observer examined the onset and progression of the Wobbler phenotype, including walking capabilities ranging from normal walking to jaw walking (unable to use forepaws), and the paw condition (from normal to curled wrists and forelimb fixed to the chest). These data indicate that the onset of disease in untreated Wobbler mice averaged 36+/-4.3 days in terms of walking and 40+/-5.7 days in terms of paw condition. HBOT significantly delayed (P<0.001 for both paw condition and walking) the onset of disease to 59+/-8.2 days (in terms of walking) and 63+/-7.6 days (in terms of paw condition). Our data suggest that HBOT significantly ameliorates mitochondrial dysfunction in the motor cortex and spinal cord and greatly delays the onset of the disease in an animal model of motor neuron disease.

Modulation of sensitivity to hyperbaric oxygen by CO2 in newborn rats.

We examined the modifying effects of CO2 on the CNS and pulmonary manifestations of hyperbaric oxygenation (HBO) in newborn rats. Four- to seven-day-old rats were exposed to HBO with inspired PCO2 (PICO2) of approximately 0, 60, 90, 140, 190, and 380 mmHg at a total pressure of 5 atm abs. The PCO2 values studied corresponded with 0, 8, 12, 18, 25, and 50 kPa, respectively, at a total pressure of 507 kPa. The O2-CO2 exposures lasted for 2-8 h. Hypercapnia at PICO2 of 60 and 90 mmHg with HBO produced extensive pulmonary damage with a high post-decompression mortality, compared to HBO alone. In contrast, PICO2 at the anesthetic levels of 140 and 190 mmHg attenuated the visible pulmonary and neurologic manifestations of O2 toxicity, and significantly reduced post-decompression mortality, compared to moderate hypercapnia of 60-90 mmHg. Supercapnia, at PICO2 of 380 mmHg, with HBO also produced no visible neurologic effect, but it caused an early apnea with severe pulmonary damage. These data indicate unique and dose-dependent cerebral and pulmonary responses to hyperoxic-hypercapnia in newborn rats. It is speculated that anesthetic levels of hypercapnia may be utilized to improve tissue oxygenation during O2 therapy in newborns, without increasing the risk of pulmonary and CNS O2 poisoning.

Experimental retinopathy by hyperbaric oxygenation.

Retinopathy of prematurity (ROP) usually occurs after a prolonged exposure to normobaric hyperoxia in newborn mammals and infants. We hypothesized that experimental ROP also could develop after acute exposures to hyperbaric oxygenation (HBO), providing that a severe and maintained retinal vasoconstriction occurred during HBO exposure. Five- to seven-day-old, Long Evans Sprague-Dawley rats were exposed for 5 h either to 5 atm abs oxygen or to 5 atm abs O2 with 190 mmHg inspired PCO2 (hypercapnia). Control rats breathed air at atmospheric pressure. Two months after exposures, rats were anesthetized, perfused intraventricularly with India ink, and retinal images were obtained. Retinal vascular density (RVD) in each image was calculated as the number of pixels in the retinal vessel area divided by the total number of pixels in the image (retinal tissue and vessels). The RVD was significantly increased from 0.0112 +/- 0.004 in the air-exposed controls to 0.0417 +/- 0.029 in the HBO-exposed rats (mean +/- SD; n = 4 in each group). HBO with hypercapnia produced a nonsignificant increase in RVD (0.0255 +/- 0.007; n = 4), reducing the HBO-induced increase in RVD by 39%. These results are consistent with the hypothesis that a sustained HBO-induced retinal vasoconstriction in newborn rats, followed by a hypoxic-ischemic injury, might result in vascular proliferation, thereby initiating ROP development on return to air. Hypercapnia does not completely prevent HBO-induced retinal vasoproliferation, probably because possible vasodilation, induced by hypercapnia, can greatly elevate retinal tissue PO2 and promote oxidative damage.

Hyperbaric oxygen tolerance in newborn mammals--hypothesis on mechanisms and outcome.

Newborn mammals, compared to adults, are extremely resistant to the CNS effects of hyperbaric oxygenation (HBO) induced by excessive generation of reactive oxygen species. This tolerance to HBO may be related to either physiological responses or the chemical characteristics of the immature brain, including a low cerebral blood flow and energy metabolism, and a low concentration of polyunsaturated fatty acids. In adult mammals the main protective mechanism against CNS oxygen toxicity, besides endogenous antioxidants, is a transient HBO-induced cerebral vasoconstriction. How cerebral vasculature reacts to HBO in the immature brain is not known. We present indirect evidence suggesting that HBO in newborn rats induces a persistent cerebral vasoconstriction concurrently with a severe and maintained reduction in ventilation. It is speculated that the outcome of these physiologic responses to hyperoxic exposures may be: (a) extension of tolerance to both CNS and pulmonary oxygen poisoning; (b) creation of a profound hypoxic-ischemic condition in vulnerable neural structures; and (c) impairment of the circulatory and ventilatory responses to hypoxic stimuli on return to air with consequent development of a secondary hypoxic-ischemic condition. These hypothetical pre- and post-HBO events may set the stage for the development of some delayed neurological disorders, including the retinopathy of prematurity and the retardation of brain development in fetuses or prematurely-born infants subjected to oxygen therapy.

Hyperbaric oxygenation alters carotid body ultrastructure and function.

We previously demonstrated that chronic normobaric hyperoxia (NH) for 60-67 h attenuated the carotid chemosensory response to hypoxia, probably initiated by the generation of reactive oxygen species (ROS). Since biological systems are affected by oxygen in a dose-dependent manner, we hypothesized that hyperbaric oxygenation (HBO) would affect the cellular mechanisms of oxygen chemoreception in a shorter time. To test the hypothesis, we studied the effects of oxygen at 5 atmospheres absolute (ATA) on cats (n = 7) carotid body ultrastructure and chemosensory responses to hypoxia, hypercapnia, and to bolus injections of cyanide, nicotine and dopamine. Four control cats breathed room air at 1 ATA. At the termination of the experiments, carotid bodies from 4 cats in each group were fixed and prepared for electron microscopy and morphometry. On the average, HBO diminished the chemosensory responsiveness to hypoxia (P < 0.01, unpaired t-test) within about 2 h, supporting the hypothesis. The responses to hypercapnia or bolus injections of cyanide, nicotine and dopamine were normal. HBO did not diminish the distribution of the dense-cored vesicles but significantly increased the mean volume-density of mitochondria and decreased the cristated area per mitochondrion in the glomus cells. The latter suggests a link between oxidative metabolism and chemosensing, and the former excludes availability of neurotransmitters being the cause of the blunted chemosensory response to hypoxia.

Free radical generation in the brain precedes hyperbaric oxygen-induced convulsions.

We tested the hypothesis that hyperbaric oxygenation (HBO) generates free radicals in the brain before the onset of neurological manifestations of central nervous system (CNS) oxygen poisoning. Chronically cannulated, conscious rats were individually placed in a transparent pressure chamber and exposed to (1) 5 atmospheres absolute (ATA) oxygen for 15 min (n = 4); (2) 5 ATA oxygen for 30 min (n = 5), during which no visible convulsions occurred; (3) 5 ATA oxygen for 30 min with recurrent convulsions (n = 6); (4) 5 ATA oxygen until the appearance of the first visible convulsions (n = 5); (5) 4 ATA oxygen for 60 min during which no convulsions occurred (n = 5); and (6) 5 ATA air for 30 min (n = 5, controls). Immediately before compression, 1 mL of 0.1 M of alpha-phenyl-N-tert-butyl nitrone (PBN) was administered intravenously (iv) for spin trapping. At the termination of each experiment, rats were euthanized by pentobarbital iv and decompressed within 1 min. Brains were rapidly removed for preparation of lipid extracts (Folch). The presence of PBN spin adducts in the lipid extracts was examined by electron spin resonance (ESR) spectroscopy. ESR spectra from unconvulsed rats exposed to 5 ATA oxygen for 30 min revealed both oxygen-centered and carbon-centered PBN spin adducts in three of the five brains. One of the five rats in this group showed an ascorbyl signal in the ESR spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of rattlesnake-venom-induced myonecrosis in mice by hyperbaric oxygen therapy.

Hyperbaric oxygen therapy (HBOT) at 1, 2, and 2.75 atmospheres absolute (ATA) was used to treat rattlesnake (Crotalus atrox) venom-induced tissue damage and edema in thigh muscles of mice. Tissue damage was evaluated by double-blind histopathologic examination: tissue edema was determined by measuring tissue water content. A total of 10 intermittent exposures to oxygen over a period of 4 days at 2 and 2.75 ATA did not influence the resolution of venom-induced tissue edema, whereas tissue damage was significantly ameliorated as compared to air-treated envenomated controls. HBOT also promoted healing in the venom-injected mice as evidenced by the presence of regenerating muscle cells. It is concluded that HBOT may limit rattlesnake venom-induced myonecrosis and promote healing in a dose-response relationship without reducing venom-induced edema.

Effects of acute hyperbaric oxygenation on respiratory control in cats.

We studied ventilatory responsiveness to hypoxia and hypercapnia in anesthetized cats before and after exposure to 5 atmospheres absolute O2 for 90-135 min. The acute hyperbaric oxygenation (HBO) was terminated at the onset of slow labored breathing. Tracheal airflow, inspiratory (TI) and expiratory (TE) times, inspiratory tidal volume (VT), end-tidal PO2 and PCO2, and arterial blood pressure were recorded simultaneously before and after HBO. Steady-state ventilation (VI at three arterial PO2 (PaO2) levels of approximately 99, 67, and 47 Torr at a maintained arterial PCO2 (PaCO2, 28 Torr) was measured for the hypoxic response. Ventilation at three steady-state PaCO2 levels of approximately 27, 36, and 46 Torr during hyperoxia (PaO2 450 Torr) gave a hypercapnic response. Both chemical stimuli significantly stimulated VT, breathing frequency, and VI before and after HBO. VT, TI, and TE at a given stimulus were significantly greater after HBO without a significant change in VT/TI. The breathing pattern, however, was abnormal after HBO, often showing inspiratory apneusis. Bilateral vagotomy diminished apneusis and further prolonged TI and TE and increased VT. Thus a part of the respiratory effects of HBO is due to pulmonary mechanoreflex changes.

Central nervous system glucose utilization rate during oxygen-induced respiratory changes at 2 atmospheres oxygen in the rat.

Hyperbaric oxygenation (HBO) at pressures higher than 3 atmospheres absolute (ATA) primarily affects the CNS, while at lower pressures, the respiratory functions are predominantly changed. Due to the outstanding respiratory manifestations of HBO at pressures lower than 3 ATA O2, the possible overlapping neurological effects of oxygen toxicity may not be easily identified. However, rats exposed for 1 and 4 h to 2 ATA O2 have shown increases in the regional cerebral metabolic rate for glucose (rCMRgl) when neither visible signs of respiratory nor nervous distress were observed. The purpose of the present study was to differentiate between the CNS and the respiratory effects of HBO at 2 ATA during development of the early signs of the respiratory distress. Changes in the rCMRgl measured by [14C]-2-deoxyglucose (2-DG) autoradiographic technique and respiratory frequency (Rf) were used as criteria for determination of CNS and respiratory effects of HBO, respectively. The results demonstrate no differences in the rCMRgl (28 major structures examined) among 3 groups of conscious rats exposed to 2 ATA O2 and normoxia at 1 and 2 ATA. At the same time a significant reduction was found in the Rf of the oxygen-exposed rats. In conclusion the respiratory system at 2 ATA O2 is apparently affected earlier than, and independent from the CNS. However, due to limited resolution power of the [14C]2-DG technique, the effect of HBO on certain undetected central respiratory control centers cannot yet be ruled out.

Effect of propranolol on cortical electrical activity in conscious and anesthetized rats.

The effect of propranolol on electrocorticographic (ECoG) activity was studied in conscious and anesthetized rats. Cortical electrodes and femoral venous cannulae were implanted 5 days before the experiments. The ECoG was recorded continuously and analyzed to different frequency bands, 2 hr before and 4 hr after the administration of propranolol. After a single infusion of 2 and 5 mg/kg or 5 consecutive daily doses of 2 mg/kg propranolol, frequent bursts of large amplitude 6-7 c/sec wave in the ECoG were observed. This ECoG phenomenon lasted between 60-100 min after the infusion of propranolol and was entirely abolished by pentobarbital anesthesia. Frequency analysis of the ECoG showed an immediate shift from predominantly delta (delta 0.5-4 c/sec) activity to overwhelmingly theta (theta 4-8 c/sec) activity following the infusion of propranolol. It is suggested that these changes in ECoG induced by propranolol are related to the sleep-enhancing and tranquilizing effects of propranolol.

Blood glucose as a predictive measure for central nervous system oxygen toxicity in conscious rats.

Blood glucose concentration was measured during continuous electrocorticographic (ECoG) recording in conscious rats exposed to 3 and 5 atmosphere absolute oxygen (ATA O2). The preconvulsive oxygen-induced ECoG changes included increased slow wave activity in delta range, followed by the appearance of successive paroxysmal electrical discharges. A correlation between increases in blood glucose concentration and ECoG changes was observed at both 3 and 5 ATA O2. No significant changes in blood glucose concentration were found in the absence of the ECoG changes. Equivalent periods of exposure to N2-O2 normoxic pressures of 1, 3, and 5 ATA did not produce changes either in ECoG or blood glucose concentration. It is therefore considered possible that an increase in blood glucose concentration may be a useful predictive measure of the ECoG manifestations of oxygen toxicity in conscious unrestrained rats. The possible mechanisms for increase in blood glucose concentration during development of brain oxygen toxicity are discussed.

Effect of propranolol on brain electrical activity during hyperbaric oxygenation in the rat.

The effect of 1, 2, and 5 mg/kg propranolol on the neuroelectrophysiological manifestations of CNS oxygen toxicity was studied in conscious rats. Cortical electrodes for electrocorticographic (ECoG) recording and femoral venous cannula for i.v. infusion were implanted 7 and 3 d, respectively, before the experiment. The rats were divided into 5 groups. Groups I to III were treated with 1, 2, and 5 mg/kg propranolol, respectively, and Group IV with saline. Groups I-IV were exposed to 5 ATA O2 until the appearance of the first cortical paroxysmal electrical discharges (FED), considered to be a preconvulsive electrophysiological manifestation of CNS oxygen toxicity. Rats in Group V were exposed to 5 ATA N2-O2 normoxia and treated with 5 mg/kg propranolol. After the hyperbaric exposures and the i.v. administration of propranolol a typical ECoG pattern consisting of frequent bursts of high amplitude spindle-like waves of 6-7 c/s activity was observed. In hyperbaric oxygen-exposed rats, the paroxysmal electrical discharges were always preceded by the propranolol-induced spindle wave activity (in theta range) and oxygen-induced slow wave activity (in delta range) in ECoG. Infusion of 2 and 5 mg/kg propranolol significantly delayed the time of onset of the oxygen-induced slow wave activity and the FED. It is suggested that the protective effect of propranolol against the neurological manifestations of oxygen toxicity, may be related to its multiple effects on physiological systems rather than beta adrenergic blocking action alone.

Effect of pentobarbital anesthesia on regional cerebral metabolic rate for glucose during hyperbaric oxygenation in rat.

Hyperbaric oxygenation (HBO) at different pressures and durations of exposure produces an increase in regional cerebral metabolic rate for glucose (rCMRgl) in conscious rats. Pentobarbital anesthesia is known to significantly reduce rCMRgl in rats during air breathing. To test if pentobarbital anesthesia is also effective in reducing HBO-induced increases in rCMRgl, the combined effect of pentobarbital anesthesia and HBO on rCMRgl was autoradiographically measured in 28 neuroanatomical structures. Two groups of rats (11 each) were chronically cannulated in one femoral artery and vein 3 days prior to the experiments. Thirty minutes before the rCMRgl measurements the rats were anesthetized with intravenous injection of 50 mg/kg pentobarbital and exposed to either 1-h air breathing at atmospheric pressure or oxygen at 2 atm absolute. No differences in rCMRgl between oxygen-exposed and air-exposed anesthetized rats were observed in 27 of the 28 neuroanatomical structures examined. The superior olivary nucleus was the only one of the 28 structures showing a significant reduction in rCMRgl following anesthesia and HBO. The possible factors involved in the elimination by anesthesia of the previously observed increases in rCMRgl in conscious rats exposed to HBO are discussed.

Regional cerebral metabolic rate for glucose immediately following exposure to two atmospheres absolute oxygen in conscious rats.

Hyperbaric oxygenation (HBO) at different pressures produces significant increases in the regional cerebral metabolic rate for glucose (rCMRgl) of various neuroanatomical structures in conscious rats. These increases in rCMRgl precede the neurological signs of oxygen toxicity. In previous studies 1- and 4-h exposures to 2 atmospheres absolute oxygen (ATA O2) produced significant increases in rCMRgl of several neuroanatomical structures. These observations are now extended to include the rCMRgl changes produced during a brief 30-min exposure to 2 ATA O2. The purpose of the present study was to investigate whether HBO has an immediate effect on rCMRgl and to determine the neuroanatomical basis of changes in brain energy metabolism during an early stage of HBO. The rCMRgl was autoradiographically measured by 2-[14C]deoxyglucose technique in conscious unrestrained rats exposed either to air at atmospheric pressure or oxygen at 2 ATA O2 for 30 min. Statistically, no significant changes in rCMRgl were observed between air-exposed and oxygen-exposed groups in the 28 neuroanatomical structures examined. It is concluded that HBO requires a certain amount of time to elicit its effect on rCMRgl in a given pressure. However, the neuroanatomical origins of the previously observed increases in rCMRgl during prolonged HBO could not be detected in this early period of exposure to 2 ATA O2.

Heparin effects during hyperbaric oxygenation in rats.

The effects of heparin were studied concurrently with development of neurological and respiratory signs of oxygen toxicity in awake unrestrained rats exposed to 3 atmosphere absolute (ATA) oxygen. The modification of the early electrophysiological manifestations of CNS oxygen toxicity by heparin in the absence of obvious signs of pulmonary oxygen toxicity was also determined at 5 ATA oxygen by electrocorticographic recording. The femoral artery of all rats was cannulated two days before the exposures to hyperbaric oxygenation (HBO), and the effect of intraarterial injection of 10 U/100g/3h heparin or an equivalent volume of saline was studied in experimental and control rats, respectively. In rats exposed to 3 ATA oxygen, the latency of the onset of the first oxygen-induced convulsions, the time interval between the first convulsion and death, and the survival time were measured. Exposure to 5 ATA oxygen was continued until the onset of the first preconvulsive paroxysmal electrical discharges (FED), considered to be an early electrophysiological indicator of CNS oxygen toxicity. The onset of convulsions was slightly delayed in heparin-treated rats exposed to 3 ATA oxygen, and the time interval between the first convulsions and death was significantly reduced in heparinized rats. No difference in survival time between heparin- and saline-treated rats was observed. Heparin significantly delayed the time of onset of the FED during exposure to 5 ATA oxygen. Gross postmortem examination of the lungs and internal organs revealed only a bloody froth in the trachea of the heparin-treated rats exposed to 3 ATA oxygen. It is concluded that the heparin-hyperoxic interaction during development of pulmonary and CNS oxygen toxicity may be related to the anticoagulant effect of heparin and hyperoxic-induced pulmonary lesions.

Regional cerebral glucose utilization rates in rats during asymptomatic period of exposure to 1, 2 and 3 atmospheres absolute of oxygen.

A previous study has shown an increase in regional cerebral metabolic rate for glucose prior to the onset of central nervous system oxygen toxicity in rats exposed to 5 atmospheres absolute of oxygen. The present study was designed to measure regional cerebral glucose utilization rates at pressures used for oxygen therapy and prolonged exposures during which rats are known to be asymptomatic. The regional metabolic rate for glucose in 26 brain structures and in gray and white matter of the thoracic and lumbar spinal cord was autoradiographically measured in awake unrestrained rats using the autoradiographic [14C]2-deoxyglucose technique. Femoral artery and vein cannulae were inserted 3 days before the experiment. Rats were divided into four groups of 15: (a) air control; (b) 6 h at 1 atmosphere absolute oxygen; (c) 4 h at 2 atmospheres oxygen; and (d) 2 h at 3 atmospheres oxygen. Statistically significant increases in glucose utilization (p less than 0.05) are seen only in lateral thalamus at 3 atmospheres oxygen, in superior olivary nucleus and inferior colliculus at 2 atmospheres oxygen and in superior olivary nucleus at 1 atmosphere oxygen. The combination of our previous data at 5 atmospheres oxygen and the present results at prolonged and safe exposures to lower pressures indicated that increased glucose utilization in some neuronal structures precedes the onset of the central nervous system manifestations of oxygen toxicity.

Regional cerebral metabolic rate for glucose during hyperbaric oxygen-induced convulsions.

Hyperbaric oxygen-induced convulsions in awake unrestrained rats are preceded by electrocorticographic changes including paroxysmal electrical discharges (PED). During oxygen induced convulsions, alterations in regional cerebral metabolic rate for glucose (rCMRgl) were autoradiographically measured and compared with rCMRgl results obtained during pre-convulsive periods in an earlier study. Statistically elevated rCMRgl during oxygen-induced convulsions were found in globus pallidus, substantia nigra, limbic structures, and cerebellar cortex. Significant reductions were found largely in auditory structures and cerebral cortex. This pattern of changes in rCMRgl resembles the pattern of changes during successive PED in the absence of overt convulsions. This similarity may indicate that a common sequence of biochemical changes leads to both oxygen-induced pre-convulsive as well as convulsive electrical discharges.

Correlation of brain glucose utilization and cortical electrical activity during development of brain oxygen toxicity.

Central nervous system (CNS) oxygen toxicity in rats is characterized by the appearance of alterations in electrical cortical activity (ECoG), followed by the appearance of paroxysmal electrical discharges and finally the onset of clinical convulsions. The correlation between the changes in ECoG and the regional cerebral metabolic rate for glucose (rCMRgl) during progressive oxygen toxicity was studied. Cortical electrodes for ECoG recording and venal arterial cannula for autoradiographic measurement of rCMRgl were chronically implanted. Using [14C]2-deoxyglucose (2-DG), the rCMRgl was measured in conscious unrestrained rats during different periods of exposure to 5 atmospheres absolute oxygen as well as an equivalent normoxic high pressure, while ECoG was continuously recorded and analyzed. A statistically significant increase in rCMRgl in 13 out of 24 investigated brain structures was found during the pre-paroxysmal electrical discharge period. This increase was accompanied by an elevation in slow and a reduction in fast ECoG frequency bands. The largest increase in rCMRgl was found in cerebellar and cerebral cortices, limbic, auditory and visual structures. Following the appearance of the first paroxysmal electrical discharge (FED) some limbic structures and cerebellar cortex showed further increases in rCMRgl, while several auditory and visual structures exhibited a significant decrease. Five atmospheres normoxic pressure had no effect on rCMRgl in any of the brain structures examined. It is concluded that pre-paroxysmal electrical discharge ECoG changes and the onset of the FED during progressive oxygen toxicity are not due to inhibition of brain energy metabolism. The possible mechanisms leading to alterations in rCMRgl during hyperbaric oxygenation are discussed.

Effects of hyperbaric oxygen on heart, brain, and lung functions in rat.

Electrocardiogram (ECG), electrocorticogram (ECoG), and respiratory rate (RR) were monitored in awake, unrestrained rats during continuous exposure to 1, 3, and 5 ATA O2 until death. The RR showed a consistent pattern at 1 and 3 ATA O2, while no pattern at 5 ATA O2 was observed. A characteristic pattern in heart rate (HR) was demonstrated at 3 ATA O2. At 5 ATA O2 a continuous reduction in HR occurred, while at 1 ATA O2 no significant change was found. The ECG at 3 ATA O2 showed various arrhythmias prior to convulsions, which were severely intensified concurrently with and following convulsions and respiratory distress. The ECG arrhythmias at 1 ATA O2 occurred after the first day of exposure and were intensified during respiratory distress and increased RR. The ECG arrhythmias at 5 ATA O2 usually occurred following the appearance of the first paroxysmal cortical electrical discharges (FED), and were extremely intensified following the onset of the first generalized clinical convulsions. Increased slow-wave activity in ECoG preceded the onset of the FED at 3 and 5 ATA O2. During days 2 and 3 at 1 ATA O2 the ECoG mostly contained slow and low-amplitude waves. The different levels of oxygen in this study often showed different effects on a particular physiological parameter. It is concluded that alterations in ECG, ECoG, HR, and RR at some pressures signal the appearance of severe pathophysiological changes during prolonged hyperbaric oxygen exposure in rats, and that the relations of these effects are not uniform at all oxygen pressures.

Frequency analysis of EEG in rats during the preconvulsive period of O2 poisoning.

The EEG of rats exposed to hyperbaric oxygenation (HBO) displays electrical discharges prior to the onset of generalized clinical convulsions (GCC). The characteristics of preconvulsive electrocorticogram (ECoG) in awake, unrestrained rats exposed to 3, 4, and 5 ATA O2 were determined. The ECoG was continuously monitored and analyzed by a hybrid analog-digital system until GCC developed. The time integral of rectified voltage of the individual delta (0.5-4 c/s), theta (4-8 c/s), alpha (8-13 c/s) beta 1 (13-20 c/s), and beta 2 (20-30 c/s) bands were plotted vs. time. An elevation in delta and a temporary reduction in alpha activity before the onset of the first electrical discharge (FED) was observed. There was a continuous reduction in beta 1 and beta 2 frequency bands during the entire pre-electrical discharge period. The activity of theta, and alpha frequency bands was significantly elevated only about 1 min before the onset of the FED, and of beta 1 and beta 2 during appearance of the FED. The possible relationship between the occurrence of preconvulsive EEG changes and pathological effects of hyperbaric oxygenation is discussed.