RESUMEN
Hyperbaric and decompression stress from diving impairs blood coagulation and fibrinolysis. We hypothesized that thromboelastography (TEG) and rotational thromboelastometry (ROTEM) were suitable to characterize the effects of stress on global hemostatic profiles. We thus conducted a comparative study of the hyperbaric effects on human coagulation using TEG and ROTEM. Maximum clot strength (maximum amplitude [MA]) and clot lysis (lysis index at time 30 minutes [LI30]) were reduced as indicated by TEG MA and EXTEM LI30, respectively. The relative changes in coagulation and fibrinolysis by the hyperbaric effects of diving were indicated by reduced TEG reaction time R at 5 hours, MA at 24 hours postdive, and reduced EXTEM coagulation time at 15 minutes postdive as well as decreased fibrinolysis (EXTEM LI30) at all postdiving time points investigated. Comparison of the parameter values and the diving-induced changes in each parameter between TEG and ROTEM showed both differences and correlations. The discrepancies between the 2 systems may be due to the different assay reagents used. Future studies will seek to further elucidate the changes in blood coagulation and fibrinolysis following varying levels of hyperbaric and decompression stress.
Asunto(s)
Enfermedad de Descompresión/sangre , Buceo/efectos adversos , Fibrinólisis , Tromboelastografía , Adolescente , Adulto , Enfermedad de Descompresión/etiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This study compared neuroendocrine and psychomotor responses in divers (D, n = 11) and non-divers (ND, n = 9) following 30-minute hyperbaric and decompression stress to 180, 300 and 450 kPa. Venous blood was drawn pre-dive and at 20 and 60 minutes post-dive and analyzed for norepinephrine (NE), epinephrine (E), tryptophan (TRP), cortisol (COR), growth hormone (GH), adrenocorticotrophic hormone (ACTH) and prolactin (PRL). Reaction time was assessed using a psychomotor vigilance task. There was no difference between groups, across time or among levels of hyperbaric stress, for NE, E, TRP or GH. Small decreases over time in COR were noted. ACTH was significantly higher for ND at 20 minutes following 180 kPa and after 60 minutes for 450 kPa exposure. PRL increased significantly more for ND, and changes from baseline following 450 kPa exposure were moderately related (r = 0.52) to the significant slowing of reaction time at 20 minutes (296 +/- 55 msec) and 60 minutes (277 +/- 35 msec) compared with baseline (247 +/- 22 msec), although PRL returned to baseline levels faster than reaction time. It was concluded that for the stress hormones measured, PRL may provide some indication of the adaptation involved with repeated hyperbaric stress, but its relationship to changes in reaction time was weak.
Asunto(s)
Descompresión/efectos adversos , Buceo/fisiología , Oxigenoterapia Hiperbárica/efectos adversos , Estrés Fisiológico/fisiología , Hormona Adrenocorticotrópica/sangre , Adulto , Análisis de Varianza , Biomarcadores/sangre , Buceo/efectos adversos , Embolia Aérea/diagnóstico , Epinefrina/sangre , Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/sangre , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , Norepinefrina/sangre , Sistema Hipófiso-Suprarrenal/fisiología , Prolactina/sangre , Tiempo de Reacción , Sistema Nervioso Simpático/fisiología , Factores de Tiempo , Triptófano/sangreRESUMEN
Nitric oxide (NO) and other reactive nitrogen species target multiple sites in the mitochondria to influence cellular bioenergetics and survival. Kinetic imaging studies revealed that NO from either activated macrophages or donor compounds rapidly diffuses to the mitochondria, causing a dose-dependent progressive increase in NO-dependent DAF fluorescence, which corresponded to mitochondrial membrane potential loss and initiated alterations in cellular bioenergetics that ultimately led to necrotic cell death. Cellular dysfunction is mediated by an elevated 3-nitrotyrosine signature of the mitochondrial complex I subunit NDUFB8, which is vital for normal mitochondrial function as evidenced by selective knockdown via siRNA. Overexpression of mitochondrial superoxide dismutase substantially decreased NDUFB8 nitration and restored mitochondrial homeostasis. Further, treatment of cells with either necrostatin-1 or siRNA knockdown of RIP1 and RIP3 prevented NO-mediated necrosis. This work demonstrates that the interaction between NO and mitochondrially derived superoxide alters mitochondrial bioenergetics and cell function, thus providing a molecular mechanism for reactive oxygen and nitrogen species-mediated alterations in mitochondrial homeostasis.
Asunto(s)
Complejo I de Transporte de Electrón/metabolismo , Endotelio Vascular/metabolismo , Fibroblastos/metabolismo , Macrófagos/metabolismo , Mitocondrias/metabolismo , Animales , Línea Celular , Complejo I de Transporte de Electrón/genética , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Humanos , Imidazoles/farmacología , Indoles/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/patología , Potencial de la Membrana Mitocondrial , Ratones , Microscopía Fluorescente , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Necrosis/genética , Óxido Nítrico/metabolismo , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Complejo Poro Nuclear/metabolismo , Subunidades de Proteína/metabolismo , ARN Interferente Pequeño/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Ratas , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
INTRODUCTION: The physical forces governing gas phase nucleation and growth in a liquid would predict less variation in the development of decompression sickness (DCS) than is known to occur in people. METHODS: In order to gain insight into the causes of biological susceptibility to DCS, we analyzed a dataset containing 250 human steady-state hyperbaric exposures using multivariate ordinal and linear regression analysis for relationships between venous gas emboli (VGE) and exposure parameters and subject characteristics. RESULTS: In both previously published data and new chamber exposure data, we found that the strongest predictor of VGE magnitude after decompression was the duration and depth of the hyperbaric exposure, as predicted. Of the subject factors, only age was significantly associated with VGE; body mass index (BMI) and gender were not. The relationship between age and VGE strengthened with decompression magnitude. DISCUSSION: These results suggest that the physiology of aging interacts with the mechanism of VGE generation, altering the risk of DCS after decompression.