During the ONR-NAVSEA Progress Review Meeting that took place in Durham from July 15-17 this summer, Stephen Thom summarized the current status of his research on circulating microparticles (MPs), which are small fragments shed by various cells that have been exposed to stress. These MPs can be found in subjects with inflammation or injury and in divers after diving.
The role of microparticles in vascular and neurological injury following decompression has been discussed in previous studies. The goals of Thom’s research, which builds on these studies, include:
- Identifying the mechanisms for MPs production;
- Determining how MPs activate neutrophiles (white blood cells associated with inflammation) and platelets;
- Assessing the roles of O2 in MPs dynamics;
- Monitoring MPs levels in humans participating in scuba activities; and
- Assessing MPs-associated changes in divers suffering from DCS.
To examine these questions, Thom conducted studies using murine DCS models, blood samples from divers and isolated cell studies. The role of MPs in murine models of DCS has been established. Mice exposed to 100 psi for two hours demonstrate increased levels of MPs and signs of DCS. In these murine studies, signs of DCS do not appear if MPs are blocked by various means. If MPs from decompressed mice are injected to animals not exposed to pressure; however, the injected animals develop signs of DCS.
The connection between MPs and DCS in divers remains unclear; however, Thom’s research does explain the mechanisms for MPs production. His team found that MPs are generated by neutrophiles during exposure to elevated gas pressure, which is the link that was previously missing.
Elevated MPs were found regularly in blood samples of divers after diving. With a series of experiments, Thom established that compression alone is sufficient to produce MPs.
Neutrophils exposed to elevated gas pressure but not to hydrostatic pressure alone, produce MPs. Various experiments have previously established the significance of nitric oxide and the related chemical reactions. Thom hypothesizes that this chain reaction is initiated by very reactive singlet oxygen, which occurs as a result of oxygen molecule electron orbital changes when it collides with inert gas molecules. The higher the pressure, the more collisions occur. And the greater the mass of inert gas molecules, the more singlet oxygen is produced. In the end, these changes result in increased MP levels. Exposure to nitrogen causes higher MPs production than exposure to helium, as the molecular mass of nitrogen is greater than that of helium.
The relationship between dive exposure and postdive MPs levels now becomes more meaningful. It appears that not all MPs have the same effects regarding DCS; in divers with DCS, there were more MPs of larger size, some of which contained gas.
Much remains to be explained about MPs and DCS. Studies are ongoing, and I surmise that MPs will remain in our scholarly focus for some time.
Post written by: Petar Denoble, MD, D.Sc.