RESUMEN
Controversial data are available on hydrogen sulfide (H2S) during hemorrhage and resuscitation, depending on timing, dosing, mode of application, and the H2S donor used. Sodium thiosulfate (Na2S2O3) is a recognized drug devoid of major side effects, which attenuated murine acute lung injury and cerebral ischemia/reperfusion injury. Therefore, we tested the hypothesis whether Na2S2O3 would mitigate organ dysfunction in porcine hemorrhage-and-resuscitation. We studied animals with pre-existing coronary artery disease because of the reduced coronary arterial expression of the H2S producing enzyme cystathionine-γ-lyase (CSE) in this prospective, randomized, controlled, blinded experimental study. 20 anesthetized and instrumented pigs underwent 3 h of hemorrhage (removal of 30 % of the blood volume and subsequent titration of mean arterial pressure to 40 mmHg). Resuscitation (72 h) comprised re-transfusion of shed blood, crystalloids, and continuous i.v. norepinephrine. Animals randomly received vehicle or Na2S2O3 (0.1 g·kg-1 h-1) for 24 h. Before, at the end of and every 24 h after shock, hemodynamics, metabolism, blood gases, lung, heart, kidney, and liver function and injury were evaluated together with cytokines and parameters of oxidative and nitrosative stress. Immediate post mortem lung, kidney, heart, and liver specimen were analyzed for marker proteins of inflammation and oxidative and nitrosative stress and mitochondrial respiratory activity in the heart, kidney, and liver. Immuno-histochemical analysis comprised lung extra-vascular albumin accumulation, nitrotyrosine formation, and CSE and glucocorticoid receptor (GCR) expression. Na2S2O3 significantly attenuated shock-induced impairment of lung mechanics and gas exchange (plateau and positive end-expiratory pressure at 72 h p = 0.0006/p = 0.0264; Horovitz index at 48 h p = 0.0261), which coincided with a higher tissue GCR expression (p = 0.0415). During resuscitation from hemorrhagic shock Na2S2O3 attenuated shock-induced acute lung injury in co-morbid swine, most likely due to a GCR expression related mechanism.
Asunto(s)
Antioxidantes/uso terapéutico , Aterosclerosis/complicaciones , Choque Hemorrágico/complicaciones , Choque Hemorrágico/tratamiento farmacológico , Tiosulfatos/uso terapéutico , Animales , Antioxidantes/administración & dosificación , Aterosclerosis/patología , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/patología , Femenino , Masculino , Distribución Aleatoria , Resucitación , Choque Hemorrágico/patología , Porcinos , Tiosulfatos/administración & dosificaciónRESUMEN
The photophysics of a dendrimer containing four donor chromophores and one acceptor chromophore are studied at the single-molecule level. Upon excitation of the donors exclusive acceptor emission is observed due to efficient Förster energy transfer. For 70% of the molecules donor emission is observed after bleaching of the acceptor, leading to a reduction of the Förster energy transfer efficiency. Furthermore, we demonstrate that in this molecular system the donor chromophores do not bleach by a triplet-sensitized photooxidation.
RESUMEN
We report on a study of a physically formed host-guest system, which was designed to be investigated by fluorescence energy transfer. All donor and acceptor molecules used were cyanine dyes. Investigation was performed at the ensemble level as well as at the single-molecule level. The ensemble measurements revealed a distribution of binding sites as well for the donor as for the acceptor. Accordingly, we found a distribution of the energy transfer efficiency. At the single-molecule level, these distributions are still present. We could discriminate entities that show very efficient energy transfer, some that do not show any energy transfer and systems whose energy transfer efficiency is only about 50%. The latter allowed the time-resolved detection of energy transfer of single entities through the acceptor decay. Finally, we discuss the observation that the energy transfer efficiency fluctuates as a function of time.