Christian J. Lambertsen

Effects of High Oxygen Pressures on the Eye

WITH the increasing use of oxygen at greater than atmospheric partial pressure for treatment of patients and for clinical research, it is inevitable that oxygen intoxication is also being induced. ...

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.

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.

Regional cerebral glucose metabolic rate during thirty minutes hypoxia of 7% oxygen in adult conscious rats.

The effect of hypoxia on the regional cerebral metabolic rate for glucose (rCMRgl) was measured in 28 neuroanatomical structures of adult, conscious, unrestrained rats by the 2-[14C]deoxyglucose autoradiographic technique. Rats were cannulated in one femoral artery and vein 3 days before the experiments. The rCMRgl was measured in 15 rats during 30 min air breathing and in 13 rats during 30 min hypoxia of 7% O2 in N2. Statistically significant increases in rCMRgl in the order of 39-95% were observed in 25 of the 28 neuroanatomical structures examined. The highest increases in rCMRgl were observed in cerebral and cerebellar white matter (95% and 60%, respectively), as well as in limbic structures ranging from a 91% increase in the septal nuclei to a 55% increase in the hypothalamus. The superior olivary nucleus and inferior colliculus (auditory structures) were the only structures which did not show changes in glucose utilization. The present data are compared with previous studies during hypoxia in conscious or anesthetized animals. It is concluded that the degree of rCMRgl response to hypoxia is affected by anesthesia, age and species.

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.

Local cerebral glucose utilization rate following intermittent exposures to 2 atmosphere absolute oxygen.

Previous studies have shown significant increases in regional cerebral metabolic rate for glucose (rCMRgl) in 14 of 28 investigated brain structures in rats exposed to 1-h oxygen at 2 atmosphere absolute (ATA O2). Continuous 4-h exposure to 2 ATA O2 resulted in significant increases only in superior olivary nucleus and inferior colliculus. In the present study, the rCMRgl was autoradiographically measured by the [14C]2-deoxyglucose technique during the last 30 min of 4 intermittent 1-h exposures to either 2 ATA O2 or air at atmospheric pressure, with 3 h of breathing air outside the pressure chamber between each oxygen or air exposure. Statistically significant reductions in rCMRgl of the oxygen-exposed rats were observed in superior olivary nucleus and inferior colliculus, while no changes were observed in 26 other investigated structures. The previously observed increases in rCMRgl in a single 1- or 4-h exposure at 2 ATA O2 were reduced or reversed during the intermittent hyperbaric oxygen exposure. The relation of the observed changes in rCMRgl during single and intermittent hyperbaric oxygen exposures to the extension of tolerance to hyperbaric oxygenation is discussed.

Kinetics of isobaric counterdiffusion

Isobaric inert gas counterdiffusion has been demonstrated to produce gas lesions in man (Lambertsen and Idicula, 1975) and lethal gas embolism in animals (Lambertsen, Cunnington and Cowley, 1975). Equations have been derived for the stable-state supersaturation pressures developing at interfaces during inert gas counterdiffusion (Graveset al., 1973). The present analysis is a mathematical treatment of the kinetics of the isobaric counterdiffusion of a pair of gases through a membrane consisting of two layers composed of substances with different diffusion coefficients and solubilities for each of the gases involved. The time to reach the stable supersaturation state due to isobaric counterdiffusion, even when circulatory transport and pulmonary washout times are included, is found to be at least an order of magnitude smaller than the time required for visible bubble formation and tissue distortion.

EFFECTS OF OXYGEN UPON OPHTHALMIC STRUCTURES

Publisher Summary This chapter focuses on most of the reported effects of O2 upon ophthalmic structures. Oxygen at high pressure can cause constriction of the retinal vessels and peripheral visual field. The chapter presents a study in which when O2 was breathed at 3 atm abs, no change in the visual fields was recorded for the first 3 h. The pathological changes involving neurosensory tissues of the eye include enzymic derangement, visual cell death, retinal detachment, cytoid body formation, and retrolental fibroplasia. The occurrence of cytoid bodies in the retinas of dogs exposed to 100% O2 at 3.0 atm abs for 4–6 h was reported. The lenticular changes in the guinea pigs consisted of pyknosis and nuclear loss in the epithelium. Changes similar to those noted in the cornea and lens of the guinea pig can potentially influence human vision on chronic or repeated exposure, if corneal edema or cataract formation occurs.

In Vitro Studies of Ovulation in the Perfused Rabbit Ovary**Supported by National Institutes of Health Grant HD-05948 and by General Research Support Grant 5S01 RR05590 (to C. J. L.).††Presented at the Thirty-First Annual Meeting of The American Fertility Society, April 3 to 5, 1975, Los Angeles, Calif.

A system has been developed for the perfusion of the rabbit ovary in vitro. At laparotomy, the ovarian artery is cannulated and perfused with M 199 tissue culture medium containing insulin and heparin, then removed with its vascular pedicle intact. Perfusion at 37 degrees C is maintained by using a capillary oxygenator and Buchler roller pump. The functional integrity of the perfused ovary is confirmed by serial determinations of the perfusate pH, glucose and lactate concentrations, and by ovarian histology. This in vitro model was used to study the mechanism of ovulation. One group of isolated rabbits received human chorionic gonadotropin (50 IU, intravenously) and, 8 hours later, one ovary was removed and perfused; the contralateral ovary remained in situ, serving as an in vivo control. Serial observations for follicle development and rupture were made over the subsequent 7-hour interval. The occurrence of ovulation in vitro was documented by time-lapse photography. In each animal, comparisons made between the in vitro and in vivo ovary indicated that the rate and time of follicle maturation and ovulation were comparable. Ovulation occurred between 10 and 15 hours after administration of human chorionic gonadotropin in both preparations.