INCREASED LEVELS OF THE BRAIN DAMAGE MARKER S100B AFTER APNEAS IN COMPETITIVE BREATH-HOLD DIVERS
Johan PA Andersson, PhD, Department of Cell and Organism Biology, Lund University, Lund, Sweden
Mats H Linér, MD, PhD, Department of Anesthesiology and Intensive Care, Lund University Hospital, Lund, Sweden
Henrik Jönsson, MD, PhD, Heart and Lung Centre, Lund University Hospital, Lund, Sweden
When observing competitions and record attempts in apnea, questions regarding the risks for brain damage easily come to mind. In four international apnea competitions between 1998 and 2004, the frequency of performances being disqualified due to loss of motor control or loss of consciousness was 4-9% (1).
S100B is a relatively brain specific, glial-derived protein, suggested to have several intra- and extracellular functions. S100B in serum is used as a brain damage marker as S100B levels increase after many types of brain damage. There is a correlation between the severity of ischemic lesions and serum levels of S100B (2). In addition to this late release, an early release has been observed. Whether this early release of S100B reflects a disruption of the blood-brain barrier or neuronal damage has been debated (3).
The possibility that a maximal-duration apnea results in a release of S100B from the brain to the blood has not been studied previously. Therefore, we investigated the magnitude and temporal patterns of serum S100B-changes after maximal-duration apneas in competitive breath-hold divers.
Nine competitive breath-hold divers volunteered to make a maximal-duration apnea during rest (‘static apnea’). The entire experiment was performed with the subject in the supine position, including a 120 min rest period post-apnea. Preparations before apneas were performed according to each subject’s normal routines, which usually included ‘warm-up apneas’ and extensive hyperventilation. The maximal-duration apnea was typically conducted after glossopharyngeal inhalation (lung packing). The subject was able to monitor breath-hold duration with the aid of a clock placed in the field of vision. Before the experiments, an arterial catheter was inserted in the radial artery at the wrist under local anesthesia. Serum levels of S100B and arterial blood gases were measured in samples collected before apnea, at the end of apnea, and at fixed intervals up to 120 min after apnea. Pre- and post-apnea S100B levels were compared using paired t-test. In six control subjects that did not perform any apneas, S100B in serum was measured at fixed times during a 120 min rest period.
The divers held their breath for an average of 5:34±0:37 (range: 4:41-6:43) min. No loss of motor control or loss of consciousness was observed after the maximal-duration apneas. Before the start of apnea, average arterial PO2 was 128±9 (108-135) mm Hg, arterial PCO2 level was 20±2 (16-24) mm Hg, and mean arterial blood pressure was 101±15 (72-120) mm Hg. At the end of apnea, arterial PO2 was 28±4 (24-39) mm Hg, arterial PCO2 was 45±4 (38-50) mm Hg, and mean arterial blood pressure was 143±25 (103-175) mm Hg. S100B in serum transiently increased within the first 10 min after the end of apnea (Fig. 1; +37%; p<0.05 compared to pre-apnea). Within 120 min, S100B levels were back to pre-apnea levels. In resting control subjects, S100B never increased above the starting level.
The brain damage marker S100B transiently increases after a prolonged, voluntary apnea in competitive breath-hold divers. The precise mechanism(s) behind the increase is not established, and could involve both neuronal damage and a temporary opening of the blood-brain barrier. We attribute the S100B increase to the asphyxia or to other physiological responses to apnea, for example, increased blood pressure.
The clinical significance of the increase is uncertain. First, the S100B levels in the present study are well below those reported after, for example, ischemic stroke and hypoxic brain damage after cardiac arrest (2). The S100B can increase by several 100% in patients affected by such conditions. Second, the early pattern of S100B changes during the first two hours after various types of brain damage is not established. In the present study, the peak in S100B occurred within the first 10 min after the apnea. After traumatic brain damage and cerebral ischemia, the peak in S100B occurs within the first hours up to 1-3 days after the event (2). Unfortunately, we were not able to follow our subjects for a comparable length of time.
It is not possible to conclude that the observed increase in S100B levels in serum in the present study reflects a serious injury to the brain, although the results raise some concerns considering negative long-term effects. Ridgway and McFarland (4) found normal results in neuropsychological tests on 21 elite apnea divers. However, a long-term follow-up study on individuals at the beginning of their careers as competitive breath-hold divers and after some years of apnea diving would be of great interest to clarify these issues. Further studies are obviously needed for the risks for brain damage in competitive breath-hold divers to be properly evaluated.
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Kapural M, Krizanac-Bengez L, Barnett G, Perl J, Masaryk T, Apollo D, Rasmussen P, Mayberg MR, Janigro D. Serum S-100beta as a possible marker of blood-brain barrier disruption. Brain Res 2002; 940(1-2):102-104.
Ridgway L, McFarland K. Apnea diving: long-term neurocognitive sequelae of repeated hypoxemia. Clin Neuropsychol 2006; 20(1):160-176.
DR. LINDHOLM: I have a question. Do you have any reference values, for example, other sports? We know that a lot of athletes use hypoxic tanks or high-altitude training. Has anyone measured S100B in terms of other sport performances?
DR. ANDERSSON: Well, there has been measurements in other sports as well; however, direct comparisons to competitive breath-hold diving I think is difficult with regard to those studies that were published, because those mostly involve traumatic head injury or whatever you should call it, like headings in soccer, boxing, running and so on, not hypoxic events. But it has been found that this brain damage marker increases also during soccer playing involving headings, also after boxing and so on. But I think then the mechanism is, what it releases is quite different. The magnitude of the increase is quite similar.
DR. LUNDGREN: Again, back to the soccer-playing kids that head the ball and then are determined to have cognitive problems down the road. It is very important to stress it because I think it is a generic problem, that the determination of mental function of one kind or another is, of course, no better than our diagnostic methods. And these kids for all appearance had not suffered any concussions. You do not feel like you have had a concussion or show signs of a concussion after hitting the ball a couple of times in a soccer match. And yet, as you stressed, the cumulative effect might be there and only show up after repeated insults.
DR. ANDERSSON: I think that is the main insight from the study. You see that we have a slight increase. But compared to acute conditions, it is a very slight increase.
DR. SMITH: This could be a normal physiologic response to severe stress. But unless you have got really long-term follow-up on cognitive function, I do not know that you could say that it is necessarily something bad. There are so many other things that change physiologically under stress. It would be interesting to know, have you ever measured free radical activity in the blood or change in blood pH, to correlate some of these other parameters?
DR. ANDERSSON: First of all, I would like to agree with you on your first comment. This is exactly what I wanted to point out. We cannot really say from this study that it is harmful. We just show that this brain damage marker increases, for what it is worth.
DR. SMITH: Do we know any more about the glial-derived protein? Do we know anything else about the specificity of the glial-derived protein? Could it have antioxidant or free radical effects? Do we know what it actually means by being released. I guess membrane cell damage like you suggested.
DR. ANDERSSON: As I said, we cannot really address the mechanism behind the release. But my guess would be that the blood-brain barrier is in some way impaired in its function so that the S100B that is found in the extracellular fluid leaks out into the serum. Whether or not that is something that could be potentially harmful in the long-term, I do not know, but at least that, to me, says that something is going on that is not within the normal physiology. The blood-brain barrier integrity is interrupted.
NOTE: To access the entire proceedings of the UHMS DAN 2006 Breath-hold Proceedings, visit Divers Alert Network.
In: Lindholm P, Pollock NW, Lundgren CEG, eds. Breath-hold diving. Proceedings of the Undersea and Hyperbaric Medical Society/Divers Alert Network 2006 June 20-21 Workshop. Durham, NC: Divers Alert Network; 2006.