Vascular leukocyte sequestration in decompression sickness and prophylactic hyperbaric oxygen therapy in rats.
BACKGROUND
Evidence for a causal relationship between decompression sickness (DCS) and leukocyte sequestration was assessed in a rat model based on the effects of interventions which impede cell-to-cell adherence, including hyperbaric oxygen therapy (HBO2).


OBJECTIVE
We hypothesized that leukocyte adhesion to vessels may play a role in DCS.


METHODS
Rats were subjected to decompression stress and their ability to ambulate on a rotating drum was assessed to quantify functional neurological deficits. Leukocyte adherence in the brain was measured by a myeloperoxidase (MPO) radioimmunoassay. Interventions included infusion of antibodies to render rats neutropenic or to inhibit leukocyte beta2 integrin adhesion molecules. Tissue gas bubbles were imaged and quantified using a transmission ultrasound camera.


RESULTS
Decompressed rats manifested a deficit in their ability to ambulate and a five-fold elevation in concentration of MPO in brain. Neutropenic rats, and those infused with antibody fragments to inhibit leukocyte beta2 integrins, did not exhibit brain MPO elevations, nor a deficit in ambulatory function. HBO2 was used in a prophylactic manner to address its ability to inhibit leukocyte beta2 integrin-mediated adherence without reducing the presence of decompression-induced bubbles. Prophylactic HBO2 prevented cerebral leukocyte sequestration and the performance deficit.


CONCLUSIONS
The results implicate beta2 integrin-mediated leukocyte adhesion in neurological deterioration after decompression stress, and offer new insight into the therapeutic action of HBO2. Immunomodulatory approaches, including prophylactic HBO2, may improve the safety of decompression procedures in undersea and space exploration.
Martin
James D
JD
Department of Emergency Medicine and Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia 19104-6068, USA.
Thom
Stephen R
SR
D000818:Animals; D001921:Brain / Q000378:metabolism; D018821:CD18 Antigens / Q000032:analysis / Q000502:physiology; D002448:Cell Adhesion; D002536:Cerebral Arteries / Q000473:pathology*; D003665:Decompression Sickness / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D006931:Hyperbaric Oxygenation; D007150:Immunohistochemistry; D007962:Leukocytes / Q000473:pathology*; D008124:Locomotion; D008297:Male; D009503:Neutropenia / Q000503:physiopathology; D009195:Peroxidase / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar
D018821:CD18 Antigens; D009195:Peroxidase