Duplessis Christopher A, Fothergill David
Navy Hospital Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA 23708, United States.
Med Hypotheses. 2008;70(3):560-6. doi: 10.1016/j.mehy.2007.04.050. Epub 2007 Sep 12.
Understanding the biochemical mechanisms influencing bubble pathophysiology may foster novel pharmacologic non-recompressive strategies that may prevent, ameliorate, and treat decompression sickness (DCS), and the injury sustained from arterial gas emboli (AGE) encountered in hyperbaric and hypobaric exposures, as well as in surgery and trauma. This review explores the biochemical effects of nitric oxide (NO) release agents, their potential impact on bubble pathophysiology, and possible use as a pharmacological intervention to reduce DCS risk and AGE injury. The hypotheses discussed contend that exogenous NO administration or mediators of endogenous NO up-regulation may reduce DCS risk and severity by mediating; (1) decreased populations of gaseous nuclei, (2) decreased bubble nuclei adherence, (3) depression of the deleterious bubble-mediated inflammatory and coagulation cascades and (4) preservation of endothelial integrity, which may defend against bubble-mediated injury. Statin medications alter numerous biochemical, and biophysical processes, which may influence bubble formation. Statins preserve endothelial integrity, reduce ischemia/reperfusion injury, and depress the interdependent inflammatory and coagulation cascades via pleiotropic properties involving up-regulation of endothelial nitric oxide synthase (eNOS) and NO. Numerous studies are researching statins, for their potential efficacy in reducing primary and secondary morbidity and mortality from cardiocerebrovascular, inflammatory (autoimmune), and infectious (sepsis) disease. Additionally, statin-mediated lipid reduction may reduce bubble generation via alterations in plasma "rheology", and surface tension. The statins are attractive potential NO release with minimal adverse side effects, and proven long-term safety, that may potentially mitigate the risk and severity of DCS. We will elaborate on the insight gained into the mechanisms proven and hypothesized for NO-mediated reductions in bubble formation, and DCS incidence and severity, with a focus on the potential for statin medications, in addition to the direct NO-donor medications such as isosorbide mononitrate and nitroglycerine.
了解影响气泡病理生理学的生化机制，可能会催生出新的非加压药理学策略，这些策略或许能够预防、改善和治疗减压病（DCS），以及在高压和低压暴露、手术及创伤中遭遇的动脉气体栓塞（AGE）所导致的损伤。本综述探讨了一氧化氮（NO）释放剂的生化效应、它们对气泡病理生理学的潜在影响，以及作为一种药理学干预措施来降低DCS风险和AGE损伤的可能用途。所讨论的假说认为，外源性给予NO或上调内源性NO的介质，可能通过介导以下过程来降低DCS风险和严重程度：（1）减少气态核的数量；（2）降低气泡核的粘附；（3）抑制有害的气泡介导的炎症和凝血级联反应；（4）维持内皮完整性，这可能抵御气泡介导的损伤。他汀类药物会改变众多可能影响气泡形成的生化和生物物理过程。他汀类药物通过涉及上调内皮型一氧化氮合酶（eNOS）和NO的多效性特性，维持内皮完整性、减少缺血/再灌注损伤，并抑制相互依存的炎症和凝血级联反应。众多研究正在探究他汀类药物在降低心脑血管、炎症（自身免疫性）和感染（脓毒症）疾病的原发性和继发性发病率及死亡率方面的潜在疗效。此外，他汀类药物介导的血脂降低可能通过改变血浆“流变学”和表面张力来减少气泡生成。他汀类药物是有吸引力的潜在NO释放剂，副作用极小且长期安全性已得到证实，可能会降低DCS的风险和严重程度。我们将详细阐述在已证实和假设的NO介导减少气泡形成、DCS发生率和严重程度的机制方面所获得的见解，重点关注他汀类药物的潜力，以及诸如单硝酸异山梨酯和硝酸甘油等直接NO供体药物。
