Biomarkers related to gas embolism: Gas score, pathology, and gene expression in a gas bubble disease model.

Fish exposed to water supersaturated with dissolved gas experience gas embolism similar to decompression sickness (DCS), known as gas bubble disease (GBD) in fish. GBD has been postulated as an alternative to traditional mammals' models on DCS. Gas embolism can cause mechanical and biochemical damage, generating pathophysiological responses. Increased expression of biomarkers of cell damage such as the heat shock protein (HSP) family, endothelin 1 (ET-1) or intercellular adhesion molecule 1 (ICAM-1) has been observed, being a possible target for further studies of gas embolism. The GBD model consisted of exposing fish to supersaturation in water with approximately 170% total dissolved gas (TDG) for 18 hours, producing severe gas embolism. This diagnosis was confirmed by a complete histopathological exam and the gas score method. HSP70 showed a statistically significant upregulation compared to the control in all the studied organs (p <0.02). Gills and heart showed upregulation of HSP90 with statistical significance (p = 0.015 and p = 0.02, respectively). In addition, HSP70 gene expression in gills was positively correlated with gas score (p = 0.033). These results suggest that gas embolism modify the expression of different biomarkers, with HSP70 being shown as a strong marker of this process. Furthermore, gas score is a useful tool to study the abundance of gas bubbles, although individual variability always remains present. These results support the validity of the GBD model in fish to study gas embolism in diseases such as DCS.

Establishment of a fish model to study gas-bubble lesions.

Decompression sickness (DCS) is a clinical syndrome caused by the formation of systemic intravascular and extravascular gas bubbles. The presence of these bubbles in blood vessels is known as gas embolism. DCS has been described in humans and animals such as sea turtles and cetaceans. To delve deeper into DCS, experimental models in terrestrial mammals subjected to compression/decompression in a hyperbaric chamber have been used. Fish can suffer from gas bubble disease (GBD), characterized by the formation of intravascular and extravascular systemic gas bubbles, similarly to that observed in DCS. Given these similarities and the fact that fish develop this disease naturally in supersaturated water, they could be used as an alternative experimental model for the study of the pathophysiological aspect of gas bubbles. The objective of this study was to obtain a reproducible model for GBD in fish by an engineering system and a complete pathological study, validating this model for the study of the physiopathology of gas related lesions in DCS. A massive and severe GBD was achieved by exposing the fish for 18 h to TDG values of 162-163%, characterized by the presence of severe hemorrhages and the visualization of massive quantities of macroscopic and microscopic gas bubbles, systemically distributed, circulating through different large vessels of experimental fish. These pathological findings were the same as those described in small mammals for the study of explosive DCS by hyperbaric chamber, validating the translational usefulness of this first fish model to study the gas-bubbles lesions associated to DCS from a pathological standpoint.

Decompressive Pathology in Cetaceans Based on an Experimental Pathological Model.

Decompression sickness (DCS) is a widely known clinical syndrome in human medicine, mainly in divers, related to the formation of intravascular and extravascular gas bubbles. Gas embolism and decompression-like sickness have also been described in wild animals, such as cetaceans. It was hypothesized that adaptations to the marine environment protected them from DCS, but in 2003, decompression-like sickness was described for the first time in beaked whales, challenging this dogma. Since then, several episodes of mass strandings of beaked whales coincidental in time and space with naval maneuvers have been recorded and diagnosed with DCS. The diagnosis of human DCS is based on the presence of clinical symptoms and the detection of gas embolism by ultrasound, but in cetaceans, the diagnosis is limited to forensic investigations. For this reason, it is necessary to resort to experimental animal models to support the pathological diagnosis of DCS in cetaceans. The objective of this study is to validate the pathological results of cetaceans through an experimental rabbit model wherein a complete and detailed histopathological analysis was performed. Gross and histopathological results were very similar in the experimental animal model compared to stranded cetaceans with DCS, with the presence of gas embolism systemically distributed as well as emphysema and hemorrhages as primary lesions in different organs. The experimental data reinforces the pathological findings found in cetaceans with DCS as well as the hypothesis that individuality plays an essential role in DCS, as it has previously been proposed in animal models and human diving medicine.