is the transition from day to night activity a risk factor for the development of cns oxygen...

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IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE ? Mirit Eynan , Michael Mullokandov, Yoav Yanir and Yehuda Arieli , Israel Naval Medical Institute

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Page 1: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS

OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE?

Mirit Eynan, Michael Mullokandov, Yoav Yanir and Yehuda Arieli, Israel Naval Medical Institute

Page 2: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Introduction• Professional and combat divers use closed-circuit

oxygen apparatus. The greatest risk involved in diving with this apparatus is the development of CNS oxygen toxicity.

• Several cases of CNS oxygen toxicity have occurred, including fatality.

• Many of these incidents occurred at a time when the divers were active during the late night hours. It is well known that night activity, such as shift work, results in deterioration of performance.

Page 3: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Introduction (cont)

• Melatonin is the primary circadian pacemaker. Its role is to synchronize the individual’s internal hormonal environment with the light-dark cycle of the external environment.

• Melatonin is also an antioxidant, playing an important role in antioxidant defense and regulating antioxidant enzyme activity and production.

Page 4: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Introduction (cont)

• Illumination of the surrounding environment during the night hours causes a reduction in melatonin levels, which exposes the organism to oxidative stress.

Page 5: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Objectives

1. To investigate in the fat sand rat (Psammomys obesus) whether a switch from day to night activity, is a risk factor for the development of CNS oxygen toxicity.

2. To search for a possible correlation between any reduction in latency to CNS oxygen toxicity at night and a concomitant reduction in melatonin levels, by assessing urinary 6-SMT excretion.

Page 6: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Fat sand rat (Psammomys obesus)1.Occupying the arid areas of Israel.2.Unlike many other rodents as rat and mouse, the fat sand rat is diurnal.

Page 7: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Methods• Each Sand-Rat was exposed to HBO at 5 ATA at

day and night (or vice versa). Latency to CNS-OT was measured from the time the oxygen level reached 95% until the appearance of the first convulsions.

• In the control phase, exposure to oxygen was during daylight hours.

• During the experimental phase, the animals were kept awake and active between the hours of 21:00 and 03:00, 5 days a week for 3 weeks.

Page 8: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Methods (Cont)

• Melatonin levels were determined by measuring urinary 6-SMT excretion.

• Urine was collected at the end of the control phase, and at the end of the experimental phase, before HBO exposure. The collection was for 24 hours at 4 hours intervals.

Page 9: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Results

Page 10: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Results

Page 11: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Methods

• To investigate the effect of melatonin we administered 50 mg/kg or ethanol + water only, to animals from both groups, 20 minuets prior to HBO exposure.

Page 12: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Results

Page 13: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Summary

• Activity during the night hours resulted in a shortening of the latency to oxygen toxicity.

• These changes were associated with deterioration of the circadian rhythm of melatonin. Acute melatonin administration however, has no effect on any of the experimental groups.

Page 14: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

Conclusion

• We conclude that a significant phase of night activity might play an additional risk factor for the development of CNS-OT.

Page 15: IS THE TRANSITION FROM DAY TO NIGHT ACTIVITY A RISK FACTOR FOR THE DEVELOPMENT OF CNS OXYGEN TOXICITY DURING HYPERBARIC OXYGEN EXPOSURE? Mirit Eynan, Michael

What comes next?

1. Means of treatment Investigate whether bright light therapy in the

morning will prolong latency to CNS-oxygen toxicity in the fat sand rat following prolonged night activity.

2. Correlation of the findings in the fat sand rat with similar parameters in oxygen divers

Investigate changes in the biochemical parameters of circadian rhythm and oxidative stress in combat divers.