Can Erythropoietin Protect the Cerebral Blood Flow and Oxygenation During Simulated Dive?

NCT00265486 | Unknown

• 1 other identifier: KF 01 271889
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

During facial cooling and especially during breath hold, can mammals - and also humans - elicit a so called dive reflex, causing bradycardia, peripheral vasoconstriction and centralization of blood flow to brain, lungs and heart but the reflex is suppressed by physical activity. The dive reflex can be elicited by breath hold alone and will be more pronounced during simultaneously facial cooling, but not by stimulation of other skin receptors. The dive reflex has an oxygen conserving effect, because of intense vasoconstriction in both viscera and muscles, and simultaneously with reduction in cardiac output (CO). Therefore plasma lactate will rise, to compensate for the lesser regional blood flow. If one hyperventilates with 100 % oxygen, then the reflex can still be elicited, but it is more pronounced during asphyxia. Experienced sports divers, who has been diving for more than 7-10 years have reduced post apnea acidosis and oxidational stress, but probably also less sensitivity for progressive hypoxia and hypercapnia, because these individuals have a more pronounced dive reflex. Transcranial Doppler ultrasonography (TCD) gives a reproducibly value for brain perfusion by continuously non-invasive real-time sampling. A single piezo-electrical transducer sends and collects ultrasound through the temporal region of the scull, where it is the thinnest. Hereby can the blood flow of arteria cerebri anterior, media (MCA) and posterior and basilaris be estimated. With TCD it can be shown that the cerebral blood flow rises in MCA in healthy subjects during facial cooling, with normal ventilation, when resting in a supine position without affecting the systemic blood pressure. Single Photon Emission Computerized Tomography (SPECT)-scanning during normo-baric and hyperbaric pressure of professional divers breathing 100 % oxygen has shown to reduce the cerebral blood flow in several regions of the brain. But it is yet unknown how brain blood flow and metabolism are affected by an "face immersion dive" and simultaneously prolonged physical activity, and hence a rise in lactate under hyperbaric pressure (3 meters), breathing atmospheric air, similar to the circumstances for trained scuba divers work. Presumably it will cause a fall in brain blood flow and in time cognitive deficits. Erythropoietin (rhEPO) is a well known drug, used as doping in sports for about 15 years. So far the only known enhancement in athletic achievement by rhEPO is caused by peripheral improvements and especially blood capability to transport oxygen to the working muscles; this has been documented by a rise in haematocrit. rhEPO has also a neuroprotective effect on neurons in patients with neuron damage caused by cerebral hypoxic ischeamia. rhEPO work also on a series of cerebral mechanisms, including enhanced motor and spatial learning and more. Enhanced motor learning may improve the professional divers choices during work and may be also physical performance and mechanical efficiency. Intravenous injection of rhEPO will increase rhEPO in cerebrospinal fluids, since rhEPO is capable of crossing blood brain. All together this may indicate that rhEPO, not only works on physical performance, but also has effects on the brain. rhEPO has also an effect on the condition of cancer and dialysis patients, not only explained by merely increased hematocrit. This project will add new knowledge in the understanding of the mechanisms of clinical use of rhEPO. The purpose of this study is to investigate, how brain blood flow and metabolism are affected by face immersion dive and simultaneously breath hold during normo-baric and hyperbaric pressure (3 m depth) when breathing atmospheric air in trained sports divers. IL-6, HSP-72, lactate, ammonium and body-temperature will be measured. Brain and muscle oxygenation will be measured by near-infrared spectroscopi (NIRS). Furthermore we will investigate whether a small dose of rhEPO affects mentioned parameters during simulated dive in pressure chamber with facial cooling. Hypothesis Brain blood flow in trained divers will be diminished during prolonged physical activity during simultaneously face immersion dive and breath hold under hyperbaric pressure. There will be a release of IL-6 and HSP-72. Pretreatment with a small amount of rhEPO before prolonged physical activity during simulated dive has a protective effect on brain blood flow and oxygenation.

Conditions

Healthy

Keywords

Divers; Brain; Flow; Blood; EPO; Dive; reflex

Interventions

Recombinant human Erythropoietin DRUG

Adm 100 U/kg sc 1 hour before completing exercise in protocol

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

12 healthy non-smoking free divers

You may qualify if:

• Age 18-40
• No smokers
• Healthy, including no history of cardiopulmonary disease
• Normal heart and lung stethoscopy
• Active diving at least twice a week
• V02max at least 15 METS
• Signed and informed consent

You may not qualify if:

• Smokers
• Any condition needing drug treatment

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Rigshospitalet

Copenhagen, Copenhagen East, 2100, Denmark

RECRUITING

Related Publications (7)

• Brines ML, Ghezzi P, Keenan S, Agnello D, de Lanerolle NC, Cerami C, Itri LM, Cerami A. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10526-31. doi: 10.1073/pnas.97.19.10526.

  PMID: 10984541 BACKGROUND

• Squadrito F, Altavilla D, Squadrito G, Campo GM, Arlotta M, Quartarone C, Saitta A, Caputi AP. Recombinant human erythropoietin inhibits iNOS activity and reverts vascular dysfunction in splanchnic artery occlusion shock. Br J Pharmacol. 1999 May;127(2):482-8. doi: 10.1038/sj.bjp.0702521.

  PMID: 10385249 BACKGROUND

• Parisotto R, Wu M, Ashenden MJ, Emslie KR, Gore CJ, Howe C, Kazlauskas R, Sharpe K, Trout GJ, Xie M. Detection of recombinant human erythropoietin abuse in athletes utilizing markers of altered erythropoiesis. Haematologica. 2001 Feb;86(2):128-37.

  PMID: 11224480 BACKGROUND

• Di Piero V, Cappagli M, Pastena L, Faralli F, Mainardi G, Di Stani F, Bruti G, Coli A, Lenzi GL, Gagliardi R. Cerebral effects of hyperbaric oxygen breathing: a CBF SPECT study on professional divers. Eur J Neurol. 2002 Jul;9(4):419-21. doi: 10.1046/j.1468-1331.2002.00436.x.

  PMID: 12099928 BACKGROUND

• Brown CM, Sanya EO, Hilz MJ. Effect of cold face stimulation on cerebral blood flow in humans. Brain Res Bull. 2003 Jun 30;61(1):81-6. doi: 10.1016/s0361-9230(03)00065-0.

  PMID: 12788210 BACKGROUND

• Kastrup A, Kruger G, Glover GH, Neumann-Haefelin T, Moseley ME. Regional variability of cerebral blood oxygenation response to hypercapnia. Neuroimage. 1999 Dec;10(6):675-81. doi: 10.1006/nimg.1999.0505.

  PMID: 10600413 BACKGROUND

• Slosman DO, De Ribaupierre S, Chicherio C, Ludwig C, Montandon ML, Allaoua M, Genton L, Pichard C, Grousset A, Mayer E, Annoni JM, De Ribaupierre A. Negative neurofunctional effects of frequency, depth and environment in recreational scuba diving: the Geneva "memory dive" study. Br J Sports Med. 2004 Apr;38(2):108-14. doi: 10.1136/bjsm.2002.003434.

  PMID: 15039241 BACKGROUND

Study Officials

• Thomas Kjeld, MD

  Rigshospitalet, dept of aneasthesiolgy, 2042, Blegdamsvej, 2100 CPH, DK

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Kjeld, MD

CONTACT

+4522361885; thomaskjeld@dadlnet.dk

Niels Secher, MD, DMSc, Prof

CONTACT

+4535452242; niels.h.secher@rh.hosp.dk

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: 1. reservelæge

Study Record Dates

• First Submitted: December 12, 2005
• First Posted: December 14, 2005
• Study Start: August 1, 2005
• Primary Completion: June 1, 2012
• Study Completion: July 1, 2012
• Last Updated: May 24, 2012

Record last verified: 2005-08

Locations

DK (1)